RESUMEN

BACKGROUND: The number of patients with Guillain-Barré syndrome (GBS) who have been observed in Curaçao, the Netherlands Antilles, may be increasing. METHODS: Clinical and serologic data were obtained from records of patients admitted between 1987 and 1999 and fulfilling National Institute of Neurological and Communicative Disorders and Stroke criteria for GBS. When possible, serum and stool samples were collected. The results were compared with a large Dutch epidemiologic study. RESULTS: The authors identified 49 patients, an overall crude incidence rate (IR) in Curaçao of 2.53/100,000 inhabitants (95% CI 1.87 to 3.35) (Dutch study 1.18, rate ratio (RR) of 2.14, p < 0.001). The IR in Curaçao increased from 1.62 in 1987 to 1991 to 3.10 in 1992 to 1999, RR 5.22 (95% CI 2.48 to 10.2, p = 0.02). The IR showed a curvilinear shape within a year. In comparison with the Dutch group, patients from Curaçao had a more severe course of the disease, with a mortality rate of 23% (3.4% in the Dutch group, p < 0.001), a higher percentage of preceding gastroenteritis (p < 0.001), and less sensory involvement (p < 0.001). In 8 of 10 serum samples, evidence was found for a recent infection with Campylobacter jejuni. CONCLUSIONS: The authors found a steady increase in incidence of GBS over the years in association with a more pronounced seasonal preponderance and a more severe course. The clinical characteristics suggest a role for C jejuni.

Asunto(s)

Infecciones por Campylobacter/mortalidad , Campylobacter jejuni , Gastroenteritis/mortalidad , Síndrome de Guillain-Barré/mortalidad , Femenino , Gastroenteritis/microbiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Antillas Holandesas/epidemiología , Estaciones del Año

RESUMEN

OBJECTIVE: To confirm an observed increase in the occurrence of Guillain-Barre syndrome (GBS) in patients in Curacao. DESIGN AND METHODS: Between 1987 and 1999, medical records of all patients who fulfilled the National Institute of Neurological Communicative Disorders and Stroke (NINCDS) criteria for GBS were reviewed. RESULTS: Forty-nine patients were diagnosed as GBS resulting in an incidence rate (IR) of 2.53/100,000 inhabitants (95 percent CI 1.87-3.35). From 1987 to 1991, the IR remained stable, whereas from 1992 to 1999, there was a linear increase in the IR. There was a high IR in the colder months and a low IR in the warmer months. Patients showed a low percentage of sensory involvement (17 percent, generally 65 percent), rapid progression of the disease (83 percent, generally 30 percent), high percentage of artificial respiration (31 percent, generally 17 percent) and high mortality rate (23 percent, generally 3-5 percent). Fifty-five percent of the patients reported a preceding gastroenteritis (GE); 9/10 serum samples showed evidence of a recent Campylobacter jejuni infection. CONCLUSIONS: This is the first report of an increase in IR of GBS over a longer period, associated with low percentage of sensory involvement, a more severe course and a high mortality rate. The characteristics suggest a role for C jejuni. Prospective research is needed to show whether the increase in GBS is due to an overall increase in IR of C. jejuni infections on the island.(Au)

Asunto(s)

Humanos , Polirradiculoneuropatía/epidemiología , Polirradiculoneuropatía/diagnóstico , Estudios de Cohortes , Estudios Prospectivos , Infecciones por Campylobacter/sangre , Antillas Holandesas/epidemiología

RESUMEN

Male Wistar rats were trained in one-trial step-down inhibitory avoidance using a 0.4-mA footshock. At various times after training (0, 1.5, 3, 6 and 9 h for the animals implanted into the CA1 region of the hippocampus; 0 and 3 h for those implanted into the amygdala), these animals received microinfusions of SKF38393 (7.5 micrograms/side), SCH23390 (0.5 microgram/side), norepinephrine (0.3 microgram/side), timolol (0.3 microgram/side), 8-OH-DPAT (2.5 micrograms/side), NAN-190 (2.5 micrograms/side), forskolin (0.5 microgram/side), KT5720 (0.5 microgram/side) or 8-Br-cAMP (1.25 micrograms/side). Rats were tested for retention 24 h after training. When given into the hippocampus 0 h post-training, norepinephrine enhanced memory whereas KT5720 was amnestic. When given 1.5 h after training, all treatments were ineffective. When given 3 or 6 h post-training, 8-Br-cAMP, forskolin, SKF38393, norepinephrine and NAN-190 caused memory facilitation, while KT5720, SCH23390, timolol and 8-OH-DPAT caused retrograde amnesia. Again, at 9 h after training, all treatments were ineffective. When given into the amygdala, norepinephrine caused retrograde facilitation at 0 h after training. The other drugs infused into the amygdala did not cause any significant effect. These data suggest that in the hippocampus, but not in the amygdala, a cAMP/protein kinase A pathway is involved in memory consolidation at 3 and 6 h after training, which is regulated by D1, beta, and 5HT1A receptors. This correlates with data on increased post-training cAMP levels and a dual peak of protein kinase A activity and CREB-P levels (at 0 and 3-6 h) in rat hippocampus after training in this task. These results suggest that the hippocampus, but not the amygdala, is involved in long-term storage of step-down inhibitory avoidance in the rat.

Asunto(s)

Amígdala del Cerebelo/efectos de los fármacos , Proteínas Quinasas Dependientes de AMP Cíclico/efectos de los fármacos , AMP Cíclico/análisis , Hipocampo/efectos de los fármacos , Memoria/fisiología , 8-Bromo Monofosfato de Adenosina Cíclica/farmacología , 8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , Animales , Benzazepinas/farmacología , Colforsina/farmacología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/análisis , Masculino , Norepinefrina/farmacología , Ratas , Ratas Wistar , Transducción de Señal

RESUMEN

Rats implanted bilaterally with cannulae in the CA1 region of the dorsal hippocampus or in the amygdala were trained in one-trial step-down inhibitory (passive) avoidance using a 0.4 mA footshock. At various times after training (0, 1.5, 3, 6 or 9 h for animals implanted in the hippocampus; 0 or 3 h for those implanted in the amygdala), they received infusions of 8-Br-cAMP (cyclic adenosine monophosphate) (1.25 micrograms/side), SKF38393 (7.5 micrograms/side), SCH23390 (0.5 microgram/side), norepinephrine ClH (0.3 microgram/side), timolol ClH (0.3 microgram/side), 8-HO-DPAT (2.5 micrograms/side), NAN-190 (2.5 micrograms/side), forskolin (0.5 microgram/side) or KT5720 (0.5 microgram/side). Rats were tested for retention 24 h after training. SKF38393 is an agonist and SCH23390 an antagonist at dopamine D1 receptors, timolol is a beta-adrenoceptor antagonist, 8-HO-DPAT is an agonist and NAN-190 an antagonist at 5HT1A receptors, forskolin enhances adenylyl cyclase, and KT5720 inhibits protein kinase A. When given into the hippocampus 0 h post-training, norepinephrine enhanced memory and KT5720 was amnestic. When given 1.5 h after training, all treatments were ineffective. When given 3 or 6 h post-training, 8-Br-cAMP, forskolin, SKF 38393, noradrenaline and NAN-190 caused memory facilitation, and KT5720, SCH23390, timolol and 8-HO-DPAT caused retrograde amnesia. At 9 h from training, all treatments were again ineffective. When given into the amygdala 0 or 3 h post-training all treatments were ineffective, except for noradrenaline at 0 h, which caused retrograde facilitation. The data agree with the suggestion that in the hippocampus, but not the amygdala, a cAMP/protein kinase A pathway is involved in memory consolidation at 3 and 6 h from training, and that this is regulated by D1, beta, and 5HT1A receptors. This correlates with a previous report of increased cAMP levels, protein kinase A activity and P-CREB levels at 3-6 h from training in rat hippocampus in this task. This may be taken to suggest that the hippocampus, but not the amygdala, is involved in the long-term storage of step-down inhibitory avoidance in the rat.

Asunto(s)

Carbazoles , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Memoria/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , 2,3,4,5-Tetrahidro-7,8-dihidroxi-1-fenil-1H-3-benzazepina/farmacología , 8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , Agonistas alfa-Adrenérgicos/farmacología , Antagonistas Adrenérgicos beta/farmacología , Amígdala del Cerebelo , Animales , Reacción de Prevención , Benzazepinas/farmacología , Colforsina/farmacología , Proteínas Quinasas Dependientes de AMP Cíclico/efectos de los fármacos , Agonistas de Dopamina/farmacología , Antagonistas de Dopamina/farmacología , Hipocampo , Indoles/farmacología , Masculino , Norepinefrina/farmacología , Piperazinas/farmacología , Pirroles/farmacología , Ratas , Ratas Wistar , Receptores Adrenérgicos beta/efectos de los fármacos , Receptores de Dopamina D1/efectos de los fármacos , Receptores de Serotonina/efectos de los fármacos , Antagonistas de la Serotonina/farmacología , Agonistas de Receptores de Serotonina/farmacología , Factores de Tiempo , Timolol/farmacología

RESUMEN

Male Wistar rats were trained in one-trial step-down inhibitory avoidance using a 0.4-mA footshock. At various times after training (0, 1.5, 3,6 and 9 h for the animals implanted into the CA1 region of the hippocampus; 0 and 3 h for those implanted into the amygdala), these animals received microinfusions of SKF38393 (7.5 mug/side), SCH23390 (0.5 mug/side), norepinephrine (0.3 mug/side), timolol (0.3 mug/side), 8-OH-DPAT (2.5 mug/side), NAN-190 (2.5 mug/side), forskolin (0.5 mug/side), KT5720 (0.5 mug/side) or 8-Br-cAMP (1.25 mug/side). Rats were tested for retention 24 h after training. When given into the hippocampus 0 h post-training, norepinephrine enhanced memory whereas KT5720 was amnestic. When given 1.5 h after training, all treatments were ineffective. When given 3 or 6 h post-training, 8-Br-cAMP, forskolin, SKF38393, norepinephrine and NAN-190 caused memory facilitation, while KT5720, SCH23390, timolol and 8-OH-DPAT caused retrograde amnesia. Again, at 9 h after training, all treatments were inffective. When given into the amygdala, norepinephrine caused retrograde facilitation at 0 h after training. The other drugs infused into the amygdala did not cause any significant effect. These data suggest that in the hippocampus, but not in the amygdala, a cAMP/protein kinase A pathway is involved in memory cosolidation at 3 and 6 h after training, which is regulated by D1, Beta, and 5HT1A receptors. This correlates with data on increased post-training cAMP levels and a dual peak of protein kinase A activity and CREB-P levels (at 0 and 3-6 h) in rat hippocampus after training in this task. These results suggest that the hippocampus, but not the amygdala, is involved in long-term storage of step-down inhibitory avoidance in the rat.

Asunto(s)

Ratas , Animales , Masculino , Amígdala del Cerebelo/efectos de los fármacos , Proteínas Quinasas Dependientes de AMP Cíclico/efectos de los fármacos , AMP Cíclico/análisis , Hipocampo/efectos de los fármacos , Memoria/fisiología , 8-Bromo Monofosfato de Adenosina Cíclica/farmacología , 8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , Benzazepinas/farmacología , Colforsina/farmacología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/análisis , Norepinefrina/farmacología , Ratas Wistar , Transducción de Señal

RESUMEN

cAMP/cAMP-dependent protein kinase (PKA) signaling pathway has been recently proposed to participate in both the late phase of long term potentiation in the hippocampus and in the late, protein synthesis-dependent phase of memory formation. Here we report that a late memory consolidation phase of an inhibitory avoidance learning is regulated by an hippocampal cAMP signaling pathway that is activated, at least in part, by D1/D5 receptors. Bilateral infusion of SKF 38393 (7.5 microg/side), a D1/D5 receptor agonist, into the CA1 region of the dorsal hippocampus, enhanced retention of a step-down inhibitory avoidance when given 3 or 6 h, but not immediately (0 h) or 9 h, after training. In contrast, full retrograde amnesia was obtained when SCH 23390 (0.5 microg/side), a D1/D5 receptor antagonist, was infused into the hippocampus 3 or 6 h after training. Intrahippocampal infusion of 8Br-cAMP (1.25 microg/side), or forskolin (0.5 microg/side), an activator of adenylyl cyclase, enhanced memory when given 3 or 6 h after training. KT5720 (0.5 microg/side), a specific inhibitor of PKA, hindered memory consolidation when given immediately or 3 or 6 h posttraining. Rats submitted to the avoidance task showed learning-specific increases in hippocampal 3H-SCH 23390 binding and in the endogenous levels of cAMP 3 and 6 h after training. In addition, PKA activity and P-CREB (phosphorylated form of cAMP responsive element binding protein) immunoreactivity increased in the hippocampus immediately and 3 and 6 h after training. Together, these findings suggest that the late phase of memory consolidation of an inhibitory avoidance is modulated cAMP/PKA signaling pathways in the hippocampus.

Asunto(s)

Proteínas Quinasas Dependientes de AMP Cíclico/fisiología , Hipocampo/fisiología , Memoria/fisiología , Transducción de Señal/fisiología , Animales , Masculino , Ratas , Ratas Wistar

RESUMEN

The hippocampus and amygdala, the entorhinal cortex and the parietal cortex participate, in that sequence, both in the formation and in the expression of memory for a step-down inhibitory avoidance task in rats. Bilateral infusion of AP5 or muscimol caused retrograde amnesia when given 0 min after training into both hippocampus and amygdala, when given or 180 min after training into the entorhinal cortex, or when given 180 min after training into the parietal cortex. Therefore, memory formation requires the sequential and integrated activity of all these areas mediated by glutamate NMDA receptors in each case. Pre-test administration of CNQX 1 day after training into hippocampus and amygdala, 1 or 31 days after training in entorhinal cortex, or 1, 31 or 60 days after training in the parietal cortex temporarily blocked retention test performance. Therefore, 1 day after training, all these brain structures are necessary for retrieval; 1 month later, the hippocampus and amygdala are no longer necessary for retrieval but the entorhinal and parietal cortex still are; and 60 days after training only the parietal cortex is needed. In all cases the mechanisms of retrieval require intact glutamate AMPA receptors.

Asunto(s)

Amígdala del Cerebelo/fisiología , Reacción de Prevención/fisiología , Mapeo Encefálico , Corteza Entorrinal/fisiología , Hipocampo/fisiología , Memoria/fisiología , Lóbulo Parietal/fisiología , 2-Amino-5-fosfonovalerato/administración & dosificación , 2-Amino-5-fosfonovalerato/farmacología , 6-Ciano 7-nitroquinoxalina 2,3-diona/administración & dosificación , 6-Ciano 7-nitroquinoxalina 2,3-diona/farmacología , Amnesia Retrógrada/inducido químicamente , Amnesia Retrógrada/fisiopatología , Animales , Conducta Exploratoria , Lateralidad Funcional , Infusiones Parenterales , Masculino , Memoria/efectos de los fármacos , Muscimol/administración & dosificación , Muscimol/farmacología , Ratas , Ratas Wistar , Tiempo de Reacción , Receptores de N-Metil-D-Aspartato/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/fisiología , Factores de Tiempo

RESUMEN

A total of 182 young adult male Wistar rats were bilaterally implanted with cannulae into the CA1 region of the dorsal hippocampus and into the amygdaloid nucleus, the entorhinal cortex, and the posterior parietal cortex. After recovery, the animals were trained in a step-down inhibitory avoidance task. At various times after training (0, 30, 60 or 90 min) the animals received a 0.5-microliter microinfusion of vehicle (saline) or 0.5 microgram of muscimol dissolved in the vehicle. A retention test was carried out 24 h after training. Retention test performance was hindered by muscimol administered into both the hippocampus and amygdala at 0 but not at 30 min posttraining. The drug was amnestic when given into the entorhinal cortex 30, 60 or 90 min after training, or into the parietal cortex 60 or 90 min after training, but not before. These findings suggest a sequential entry in operation, during the posttraining period, of the hippocampus and amygdala, the entorhinal cortex, and the posterior parietal cortex in memory processing.

Asunto(s)

Amígdala del Cerebelo/fisiología , Corteza Entorrinal/fisiología , Hipocampo/fisiología , Memoria/fisiología , Lóbulo Parietal/fisiología , Amígdala del Cerebelo/efectos de los fármacos , Animales , Corteza Entorrinal/efectos de los fármacos , Agonistas del GABA/farmacología , Hipocampo/efectos de los fármacos , Masculino , Muscimol/farmacología , Lóbulo Parietal/efectos de los fármacos , Ratas , Ratas Wistar

RESUMEN

A total of 182 young adult male Wistar rats were bilaterally implanted with cannulae into the CA1 region of the dorsal hippocampus and into the amygdaloid nucleus, the entorhinal cortex, and the posterior parietal cortex. After recovery, the animals were trained in a stepdown inhibitory avoidance task. At various times after training (0, 30, 60 or 90 min) the animals received a 0.5-mul microinfusion of vehicle (saline) or O.5 mug of muscimol dissolved in the vehicle. A retention test was carried out 24 h after training. Retention test performance was hindered by muscimol administered into both the hippocampus and amygdala at 0 but not at 30 min posttraining. The drug was amnestic when given into the entorhinal cortex 30, 60 or 90 min after training, or into the parietal cortex 60 or 90 min after training, but not before. These findings suggest a sequential entry in operation, during the posttraining period, of the hippocampus and amygdala, the entorhinal cortex, and the posterior parietal cortex in memory processing.

Asunto(s)

Ratas , Masculino , Animales , Amígdala del Cerebelo/fisiología , Corteza Entorrinal/fisiología , Hipocampo/fisiología , Memoria/fisiología , Muscimol/farmacología , Lóbulo Parietal/fisiología , Amígdala del Cerebelo/efectos de los fármacos , Corteza Entorrinal/efectos de los fármacos , Hipocampo/efectos de los fármacos , Lóbulo Parietal/efectos de los fármacos , Ratas Wistar

RESUMEN

Rats were trained in a step-down inhibitory avoidance task and tested for retention 1, 31, or 60 days later. Three to 7 days prior to testing, they were bilaterally implanted with cannulae in the CA1 region of the dorsal hippocampus and in the amygdaloid nucleus (H + A), in the entorhinal cortex (EC), and in the posterior parietal cortex (PPC). Ten minutes prior to testing, the animals received, through the cannulae, 0.5-microliter microinfusions of vehicle (20% dimethylsulfoxide in saline) or of 0.5 microgram of CNQX dissolved in the vehicle. A second test session was carried out 90 min after the first. CNQX blocked retention test performance when given into H + A 1 day after training but not later; when given into EC 1 or 31 days after training, but not later; and when given into PPC 1, 31, or 60 days after training. In all cases performance returned to normal levels in the second test session. The data suggest that H and A are involved in memory expression for only a few days after acquisition; that EC is involved in memory expression for up to 31, but less than 60, days after acquisition; and that PPC is involved in memory expression for up to at least 2 months after acquisition.

Asunto(s)

6-Ciano 7-nitroquinoxalina 2,3-diona/farmacología , Amígdala del Cerebelo/efectos de los fármacos , Encéfalo/fisiología , Hipocampo/efectos de los fármacos , Memoria/fisiología , Animales , Mapeo Encefálico , Masculino , Ratas , Ratas Wistar , Factores de Tiempo

RESUMEN

Rats bilaterally implanted with cannulae in the CA1 region of the dorsal hippocampus and/or in the amygdaloid nucleus, in the entorhinal cortex, and in the posterior parietal cortex, were trained in a step-down inhibitory avoidance task. At various times after training (immediately, 30, 60 or 90min) they received, through the cannulae, 0.5µl microinfusions of saline or of 5.0µg of AP5 dissolved in saline. A retention test was carried out 24h after training. Retention test performance was hindered by AP5 given into hippocampus, amygdala, or both hippocampus and amygdala immediately but not 30min post-training. The drug was amnestic when given into the entorhinal cortex 30, 60 or 90min after training, or into the parietal cortex 60 or 90min after training, but not at earlier times. The findings suggest a sequential entry in operation, in the post-training period, of NMDA-receptor mediated mechanisms involved in memory processing; first in hippocampus and amygdala, 30min later in entorhinal cortex, and 30min later in posterior parietal cortex.

RESUMEN

Platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), which is thought to be a retrograde messenger in long-term potentiation (LTP), enhances glutamate release and LTP through an action on presynaptic nerve endings. The PAF antagonist BN 52021 blocks CA1 LTP in hippocampal slices, and, when infused into rat dorsal hippocampus pre- or posttraining, blocks retention of inhibitory avoidance. Here we report that memory is affected by pre- or posttraining infusion of the PAF analog 1-O-hexadecyl-2-N-methylcarbamoyl-sn-glycerol-3-phosphocholine (mc-PAF) into either rat dorsal hippocampus, amygdala, or entorhinal cortex. Male Wistar rats were implanted bilaterally with cannulae in these brain regions. After recovery from surgery, the animals were trained in step-down inhibitory avoidance or in a spatial habituation task and tested for retention 24 h later. mc-PAF (1.0 microgram per side) enhanced retention test performance of the two tasks when infused into the hippocampus before training without altering training session performance. In addition, mc-PAF enhanced retention test performance of the avoidance task when infused into (i) the hippocampus 0 but not 60 min after training; (ii) the amygdala immediately after training; and (iii) the entorhinal cortex 100 but not 0 or 300 min after training. In confirmation of previous findings, BN 52021 (0.5 microgram per side) was found to be amnestic for the avoidance task when infused into the hippocampus or the amygdala immediately but not 30 or more minutes after training or into the entorhinal cortex 100 but not 0 or 300 min after training. These findings support the hypothesis that memory involves PAF-regulated events, possibly LTP, generated at the time of training in hippocampus and amygdala and 100 min later in the entorhinal cortex.

Asunto(s)

Amígdala del Cerebelo/fisiología , Reacción de Prevención/fisiología , Diterpenos , Hipocampo/fisiología , Memoria/fisiología , Factor de Activación Plaquetaria/farmacología , Amígdala del Cerebelo/efectos de los fármacos , Animales , Reacción de Prevención/efectos de los fármacos , Ginkgólidos , Habituación Psicofisiológica , Hipocampo/efectos de los fármacos , Técnicas In Vitro , Infusiones Parenterales , Lactonas/administración & dosificación , Lactonas/farmacología , Potenciación a Largo Plazo/efectos de los fármacos , Masculino , Memoria/efectos de los fármacos , Factor de Activación Plaquetaria/administración & dosificación , Factor de Activación Plaquetaria/antagonistas & inhibidores , Células Piramidales/efectos de los fármacos , Células Piramidales/fisiología , Ratas , Ratas Wistar , Valores de Referencia , Percepción Espacial , Factores de Tiempo

RESUMEN

Nitric oxide (NO) has been proposed to be involved in the induction of long-term potentiation (LTP) and in other processes. When coupled with weak tetanic stimulation, NO produces a long-term synaptic enhancement on its own. N-Nitroarginine (NO-Arg) inhibits NO-synthase, the enzyme that produces NO, and blocks LTP in hippocampal slices. We investigated the effect on memory of the pre- or post-training infusion of NO-Arg and of the post-training infusion of the No donor, S-nitroso-N-acetylpenicillamine (SNAP) into the hippocampus. Male Wistar rats were implanted bilaterally with cannulae in the dorsal hippocampus. After recovery from surgery, the animals were trained in step-down inhibitory avoidance using a 0.4-mA footshock and tested for retention 24 h later. NO-Arg (2.0 microgram) hindered retention test performance when infused either before or immediately after training, but not 30 or 60 min later. SNAP (5.0 microgram) enhanced retention test performance when given 0, 60, or 150 min, but not 300 min, after training. The results suggest that memory storage depends on NO-sensitive processes in the hippocampus, perhaps, as suggested in previous papers, LTP generated at the time of training.

Asunto(s)

Hipocampo/fisiología , Potenciación a Largo Plazo/fisiología , Recuerdo Mental/fisiología , Óxido Nítrico/fisiología , Animales , Reacción de Prevención/fisiología , Mapeo Encefálico , Masculino , Ratas , Ratas Wistar , Tiempo de Reacción/fisiología , Retención en Psicología/fisiología

RESUMEN

Zinc protoporhyrin-9 (ZnPP) is an inhibitor of heme oxygenase, the enzyme involved in the biosynthesis of carbon monoxide (CO). CO regulates the activity of glutamatergic synapses and has been proposed to play a role in the early phases of long-term potentiation. The present paper reports on the effect of ZnPP on memory of inhibitory avoidance and of habituation to a novel environment. The bilateral infusion of ZnPP (2 micrograms/side) into the dorsal hippocampus caused amnesia for the inhibitory avoidance task when given before training or 0 or 30 min, but not 60 or 100 min, after training. The immediate post-training intrahippocampal infusion of ZnPP also caused amnesia for the habituation task. The immediate post-training intra-amygdala infusion of ZnPP had no effect on retention of the avoidance task. The data are consistent with the hypotheses that memory involves long-term potentiation initiated at the time of training in the hippocampus, and that hippocampal but not amygdala long-term potentiation may be regulated by CO.

Asunto(s)

Amnesia Retrógrada/inducido químicamente , Amígdala del Cerebelo/fisiología , Hemo Oxigenasa (Desciclizante)/antagonistas & inhibidores , Hipocampo/fisiología , Protoporfirinas/farmacología , Amnesia Retrógrada/psicología , Animales , Reacción de Prevención/efectos de los fármacos , Habituación Psicofisiológica/efectos de los fármacos , Inyecciones , Potenciación a Largo Plazo/efectos de los fármacos , Masculino , Protoporfirinas/administración & dosificación , Ratas , Ratas Wistar

RESUMEN

Platelet-activating factor (PAF) is present in the brain. It enhances glutamate release and long-term potentiation (LTP) through an action on synaptic membrane receptors sensitive to the antagonist, BN 52021, and has been proposed as a retrograde messenger in the genesis of LTP. In addition, PAF has other, metabolic actions mediated by microsomal receptors sensitive to the antagonist, BN 50730. We investigated the effect on memory of the pre- or post-training infusion of BN 52021 or BN 50730 into the hippocampus and that of BN 52021 in the amygdala and the entorhinal cortex. Male Wistar rats were implanted bilaterally with cannulae aimed at these brain regions. After recovery from surgery, the animals were trained in step-down inhibitory avoidance using a 0.5-mA foot shock and tested for retention 24 h later. BN 52021 (0.5 microgram/side) was amnestic when given into the hippocampus or the amygdala either before or immediately after training but not 30 or 100 min later. BN 52021 was also amnestic when given into the entorhinal cortex 100 but not 0 or 300 min after training. Intrahippocampally administered BN 50730 had no effect on memory. The findings are compatible with the suggestion from previous findings that memory of this task depends on the generation of LTP at the time of training in hippocampus and amygdala and, 90-180 min later, in the entorhinal cortex.

Asunto(s)

Reacción de Prevención/efectos de los fármacos , Diterpenos , Lactonas/farmacología , Memoria/efectos de los fármacos , Factor de Activación Plaquetaria/antagonistas & inhibidores , Inhibidores de Agregación Plaquetaria/farmacología , Amígdala del Cerebelo/efectos de los fármacos , Animales , Ginkgólidos , Glutamatos/metabolismo , Hipocampo/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Membranas Sinápticas/efectos de los fármacos

RESUMEN

This experiment investigated the effect on memory, in rats, of the bilateral intrahippocampal post-training infusion of the glutamate metabotropic receptor (mGLUR) agonist, ACPD (1S, 2R-aminocyclopentane dicarboxylate) and of the mGLUR antagonist, MCPG ([RS]-alpha-methyl-4-carboxyphenyl glycine). Male Wistar rats were implanted bilaterally with cannulae in the CA1 region of the dorsal hippocampus. After recovery from surgery they were trained in a step-down inhibitory avoidance task and tested for retention 24h later. Immediately or 180min after training they received a bilateral intrahippocampal infusion of saline (0.5µl), ACPD (1.0 or 2.5µg/side), MCPG (2.5µg/side) or ACPD plus MCPG, in 0.5µl saline. Upon immediate post-training infusion, ACPD caused a dose-dependent enhancement of memory and MCPG was amnestic. The effect of MCPG was antagonized by the simultaneous administration of ACPD. When given 180min after training, the drugs had no effect on memory. The results indicate that the early phase of memory is regulated by mGLURs in the hippocampus, and support the suggestion that memory involves long-term potentiation initiated at the time of training in the hippocampus.

RESUMEN

Rats were trained in a step-down inhibitory avoidance task using a 0.8-mA foot shock and tested for retention 26 days later. Three to five days prior to the retention test they were bilaterally implanted with cannulae aimed at the entorhinal cortex. Ten minutes before testing they received an infusion, into the entorhinal cortex, of vehicle, ciano-nitro-quinoxaline-dione (CNQX; 0.5 micrograms), amino-hydroxy-methyl-isoxalone-propionate (AMPA; 1.0 or 2.5 micrograms), or AMPA (1.0 micrograms) plus CNQX (0.5 micrograms). CNQX blocked memory expression; the effect lasted less than 90 min. AMPA had no effect of its own, but at the lower dose level it counteracted the depressant influence of CNQX. It is not likely that the effect of CNQX could have been due to an influence on performance: In separate sets of experiments the bilateral intraentorhinal infusion of CNQX (0.5 micrograms) 10 min before training did not affect either acquisition or retention of the avoidance task or general activity during 3 min of free exploration in the training box. The results indicate that the integrity of AMPA receptors in the entorhinal cortex is necessary for memory expression.

Asunto(s)

Hipocampo/fisiología , Memoria/efectos de los fármacos , Quinoxalinas/farmacología , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico/farmacología , 6-Ciano 7-nitroquinoxalina 2,3-diona , Animales , Reacción de Prevención/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Conducta Exploratoria/efectos de los fármacos , Inyecciones , Actividad Motora/efectos de los fármacos , Quinoxalinas/administración & dosificación , Quinoxalinas/antagonistas & inhibidores , Ratas , Ratas Wistar , Receptores AMPA/efectos de los fármacos , Receptores AMPA/fisiología

RESUMEN

We investigated the effect of a bilateral post-training intracerebral infusion of KN62, a specific inhibitor of calcium/calmodulin-dependent protein kinase II (CaM-II), on memory. This enzyme plays a crucial role in the early phases of long-term potentiation. Male Wistar rats were implanted bilaterally with cannulae aimed at the CA1 region of the dorsal hippocampus or at the junction between the central and the basolateral nuclei of the amygdala. After recovery, rats were trained in step-down inhibitory avoidance using a 0.5-mA footshock and tested for retention 24 h later. At various times after training (0, 30, 120, or 240 min for the animals implanted into the hippocampus; 0 or 240 min for the animals implanted in the amygdala) they received, through the cannulae, an infusion of vehicle (0.1% dimethylsulfoxide in water) or KN62 (100 mumol/side). KN62 caused full retrograde amnesia when given 0 min after training into either the amygdala or the hippocampus. When given into the hippocampus 30 min post-training it had a partial amnestic effect. When given 120 min after training into the hippocampus, or 240 min after training into either structure, KN62 had no effect. The data suggest that the early phase of memory requires intact CaM-II activity in the amygdala and hippocampus and support the hypothesis that memory involves long-term potentiation initiated at the time of training in both structures.

Asunto(s)

1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/análogos & derivados , Amnesia Retrógrada/inducido químicamente , Amígdala del Cerebelo/efectos de los fármacos , Proteínas Quinasas Dependientes de Calcio-Calmodulina/antagonistas & inhibidores , Hipocampo/efectos de los fármacos , Isoquinolinas/efectos adversos , Isoquinolinas/farmacología , Piperazinas/efectos adversos , Piperazinas/farmacología , Animales , Reacción de Prevención/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Retención en Psicología/efectos de los fármacos

RESUMEN

Rats were bilaterally implanted with cannulae in the entorhinal cortex, amygdala, and hippocampus; after recovery, they were trained in a step-down inhibitory avoidance task and tested for retention 24 h later. Muscimol (0.03 microgram) or D-amino-5-phosphonovalerate (5.0 micrograms) infused in the entorhinal cortex 20 min prior to training inhibited the amnestic effect of the same dose of muscimol infused into this area 100 min after training. Thus, memory-relevant information must be processed by the entorhinal cortex at the time of training in order that this cortex may play a late post-training role in memory processing. Pretraining intraentorhinal muscimol administration did not affect the amnestic effect of the post-training infusion of muscimol into the amygdala and hippocampus, or the inhibition of memory expression induced by a pretest infusion of CNQX into the amygdala and hippocampus or into the entorhinal cortex. Pretest intraentorhinal muscimol also did not influence the effect of pretest intra-amygdala and intrahippocampal CNQX administration. These data indicate that the cells of the entorhinal cortex that are sensitive to pretraining muscimol are not part of the inputs that lead to post-training processing by the amygdala and hippocampus, or to the intervention of the amygdala, hippocampus, and entorhinal cortex in memory expression. The present findings are compatible with the possibility that, instead, the entorhinal cortex may be an output of the amygdala and hippocampus at the time of memory expression.

Asunto(s)

Amígdala del Cerebelo/fisiología , Hipocampo/fisiología , Sistema Límbico/fisiología , Recuerdo Mental/fisiología , Muscimol/farmacología , Receptores de GABA-A/fisiología , 2-Amino-5-fosfonovalerato/farmacología , 6-Ciano 7-nitroquinoxalina 2,3-diona , Amígdala del Cerebelo/efectos de los fármacos , Animales , Reacción de Prevención/efectos de los fármacos , Reacción de Prevención/fisiología , Electrochoque , Hipocampo/efectos de los fármacos , Sistema Límbico/efectos de los fármacos , Potenciación a Largo Plazo/efectos de los fármacos , Potenciación a Largo Plazo/fisiología , Masculino , Recuerdo Mental/efectos de los fármacos , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiología , Quinoxalinas/farmacología , Ratas , Ratas Wistar , Tiempo de Reacción/efectos de los fármacos , Tiempo de Reacción/fisiología , Receptores de GABA-A/efectos de los fármacos , Retención en Psicología/efectos de los fármacos , Retención en Psicología/fisiología

RESUMEN

The background, design and preliminary results of the Dutch Guillain-Barré trial comparing high-dose immunoglobulins (IgIV) with plasma-exchange (PE) are described. This randomized trial was conservative in that the main aim was to show equal effect of both treatments within certain predefined limits. This approach was appropriate since IgIV is quickly and easily applicable, whereas PE is much more combersome leading to treatment delays and a considerable dropout rate. Moreover PE is not available in all hospitals. For these reasons IgIV would be preferable if the two treatments have a similar effect. We originally estimated that 200 patients would be needed to demonstrate a comparable effect of IgIV and PE (type I error = 0.05 and type II error = o.2). At the interim analysis after 150 patients the stopping criterion has been met. Four weeks after randomization 52.7 per cent in the IgIV group was functionally improved and 34.2 per cent in the PE-group, and advantage of 18.5 per cent for IgIV (p = 0.024)

Asunto(s)

Humanos , Masculino , Femenino , Inmunoglobulinas Intravenosas/administración & dosificación , Plasmaféresis , Polirradiculoneuropatía/terapia , Inmunoglobulinas Intravenosas/uso terapéutico