RESUMEN
Chronic continuous cocaine treatment produces a unique pattern of locomotor activation over time. An initial, progressive increase in locomotion is indicative of sensitization. Unlike intermittent cocaine, this increase is subsequently reversed during the continuous exposure, and activity returns to pre-sensitization levels within days. To study the pharmacological mechanisms that underlie this phenomenon, osmotic minipumps containing cocaine or selective uptake inhibitors of dopamine (GBR 12909 or RTI-117), serotonin (fluoxetine), or norepinephrine (nisoxetine) were implanted into rats. Locomotor activity was measured for 1 h each day, beginning 4 h after pumps were implanted. In the cocaine group, activity was significantly elevated on the first day, peaked between the second and third days, then decreased to a plateau which remained significantly above control levels through 14 days. Peak activity in the GBR 12909 and RTI-117 animals occurred on the first day, followed by a significant decrease 24-48 h later, but not complete tolerance. Neither fluoxetine nor nisoxetine altered locomotor activity. The selective dopamine uptake inhibitors produced some of the effects of cocaine. The possibilities that cocaine interacts with the dopamine transporter in a qualitatively different manner from that of these selective dopamine uptake inhibitors, or that other monoamine systems are involved, are discussed.
Asunto(s)
Cocaína/farmacología , Inhibidores de Captación de Dopamina/farmacología , Actividad Motora/efectos de los fármacos , Inhibidores de Captación Adrenérgica/farmacología , Animales , Cocaína/administración & dosificación , Cocaína/análogos & derivados , Inhibidores de Captación de Dopamina/administración & dosificación , Tolerancia a Medicamentos , Fluoxetina/análogos & derivados , Fluoxetina/farmacología , Bombas de Infusión Implantables , Masculino , Inhibidores de la Monoaminooxidasa/farmacología , Piperazinas/farmacología , Ratas , Ratas Sprague-Dawley , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Factores de TiempoRESUMEN
U-69593, the selective K-opioid agonist, was repeatedly administered in single daily injections (0.32 mg/kg) to male, Sprague-Dawley rats. Two or ten days later, the rats were euthanized and dopamine D1 and D2 receptors were measured using (3H]SCH 23390 or [3H]sulpiride, respectively, in caudate putamen and nucleus accumbens. Two days after the last of three injections, dopamine D2 receptors in the caudate putamen were decreased by approximately 40%, with no change in D1 receptors. Dopamine D2 receptor number had returned to normal by 10 days posttreatment. In contrast, in the nucleus accumbens there was a small, nonsignificant decrease in dopamine D2 receptors 2 days after treatment, but a large increase (65%) after 10 days. In agreement with the changes in D2 receptors, there was a significant downward shift in the locomotor activity curve for the D2 agonist quinpirole after a 2-day withdrawal. There were no differences in either the total amount of dopamine taken up or in the IC50 for cocaine to inhibit dopamine uptake following this treatment, suggesting that the dopamine transporter and presynaptic terminals were intact. The results of these studies demonstrate that repeated administration of a selective K-opioid agonist induces long-term alterations in dopamine D2 receptors. Furthermore, the finding that these changes in receptor number require both repeated injections and a withdrawal time greater than 1 day suggests that these alterations are compensatory in nature.
Asunto(s)
Bencenoacetamidas , Núcleo Caudado/fisiología , Glicoproteínas de Membrana , Proteínas de Transporte de Membrana , Proteínas del Tejido Nervioso , Núcleo Accumbens/fisiología , Putamen/fisiología , Pirrolidinas/farmacología , Receptores de Dopamina D2/metabolismo , Receptores Opioides kappa/antagonistas & inhibidores , Sinapsis/fisiología , Animales , Benzazepinas/farmacocinética , Proteínas Portadoras/metabolismo , Núcleo Caudado/efectos de los fármacos , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Regulación hacia Abajo , Esquema de Medicación , Masculino , Actividad Motora/efectos de los fármacos , Núcleo Accumbens/efectos de los fármacos , Putamen/efectos de los fármacos , Quinpirol/farmacología , Ratas , Ratas Sprague-Dawley , Receptores de Dopamina D3 , Sulpirida/farmacocinética , Sinapsis/efectos de los fármacos , Factores de TiempoRESUMEN
Chronic cocaine administration can produce tolerance or sensitization to locomotor activating effects, depending on the treatment paradigm. The effects of chronic, continuous cocaine were measured on locomotor activity for 1 hr daily for 7 days. Cocaine produced significant increases in locomotor activity 4 hr after osmotic minipumps were implanted, and an even higher level of activity after 24 hr. This was likely a rapid sensitization to the locomotor activating effects of cocaine, because neither brain nor plasma levels of cocaine were significantly altered over the treatment period. By day 4, activity levels diminished, but remained significantly higher than in saline-treated animals. Twenty-four hr after pump removal, there were no changes in dopamine D1 or D2 receptor binding, or in dopamine-stimulation of adenylyl cyclase activity in either caudate putamen or nucleus accumbens of cocaine-treated animals. Chronic naltrexone produced a slight, nonsignificant decrease in locomotor activity and when combined with cocaine, produced the same pattern of activity as cocaine alone, but with slightly less stimulation on all days. Morphine produced a smaller increase in activity than cocaine that remained constant throughout the treatment week. Cocaine with morphine was additive, producing greater activity and less tolerance than cocaine alone. Thus, continuous cocaine administration produces a rapid sensitization that is lost over the course of the treatment period, yet does not produce any immediate alterations in dopamine receptors or regulation of adenylyl cyclase. The pattern of behavior is not altered by an opioid antagonist, while the sensitization period appears to be prolonged in the presence of an opioid agonist.
Asunto(s)
Analgésicos Opioides/farmacología , Cocaína/farmacología , Inhibidores de Captación de Dopamina/farmacología , Actividad Motora/efectos de los fármacos , Receptores Dopaminérgicos/efectos de los fármacos , Adenilil Ciclasas/metabolismo , Animales , Cocaína/sangre , Dopamina/farmacología , Inhibidores de Captación de Dopamina/sangre , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Activación Enzimática , Masculino , Núcleo Accumbens/enzimología , Ratas , Ratas Sprague-Dawley , Receptores Dopaminérgicos/metabolismoRESUMEN
The chronic continuous infusion of cocaine produces partial behavioral tolerance to cocaine and tolerance to the inhibition of dopamine uptake by cocaine, without changing dopamine transporter binding. In order to examine more closely the dopaminergic contribution to this effect, the selective dopamine uptake inhibitor GBR 12,909 (30 mg/kg/day), cocaine (50 mg/kg/day), or vehicle, were continuously infused via osmotic minipump, and their effects on the dopamine transporter examined. Drug and vehicle pumps were implanted into male Sprague-Dawley rats and removed after seven days. [3H]WIN 35,428 binding and [3H]dopamine uptake were measured in caudate putamen and nucleus accumbens at varying intervals after pump removal. The Bmax for [3H]WIN 35,428 binding was decreased by approximately 75% in the caudate putamen and by 40% in the nucleus accumbens of GBR 12,909-treated rats both 1 and 4 days after pump removal, and was still significantly decreased after 10 days, but had returned to normal by 20 days post-treatment. In contrast, cocaine did not significantly alter [3H]WIN 35,428 binding. GBR 12,909 produced both tolerance to the inhibition of [3H]dopamine uptake by cocaine, and a decrease in total uptake of dopamine, in the caudate putamen, with no change in the nucleus accumbens. The persistent reduction of [3H]WIN 35,428 binding following continuous GBR 12,909 does not appear to result from residual drug binding. These findings suggest that GBR 12,909 and cocaine may bind to and regulate the dopamine transporter in different ways.
Asunto(s)
Encéfalo/efectos de los fármacos , Cocaína/farmacología , Inhibidores de Captación de Dopamina/farmacología , Dopamina/metabolismo , Piperazinas/farmacología , Animales , Encéfalo/metabolismo , Cocaína/análogos & derivados , Cocaína/metabolismo , Inhibidores de Captación de Dopamina/administración & dosificación , Masculino , Piperazinas/administración & dosificación , Ratas , Ratas Sprague-DawleyRESUMEN
On gestational day 7 pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (initial dose, 9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that they were exposed to methadone prenatally and/or postnatally. On postnatal day 21, dopamine (DA), norepinephrine (NE), serotonin (5-HT), and their metabolites were analyzed. Perinatal methadone exposure disrupted dopaminergic, noradrenergic, and serotonergic activity in a brain region- and gender-specific fashion. The ratio of the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) to DA was reduced in the frontal cortex of males exposed to methadone postnatally. No effects of perinatal methadone exposure were observed on DA and DOPAC in the striatum. The ratio of 3-methoxy-4-hydroxyphenylglycol (MOPEG) to NE in the hippocampus was increased significantly in males exposed to methadone prenatally. Striatal and parietal cortical 5-hydroxyindoleacetic acid (5-HIAA), but not its ratio to 5-HT, was increased slightly in rats exposed to methadone postnatally. Although parietal cortical 5-HT, 5-HIAA, and 5-hydroxytryptophan were all affected by perinatal methadone exposure, the ratios of metabolite and precursor to 5-HT were not affected. Effects of methadone exposure appeared to depend upon the developmental stage at which exposure occurred and did not appear to result from the phenomenon of neonatal withdrawal. Changes in activity of these three neurotransmitter systems may contribute to the effect of perinatal methadone on the activity of other neurons, such as cholinergic neurons.
Asunto(s)
Encéfalo/efectos de los fármacos , Dopamina/metabolismo , Metadona/farmacología , Narcóticos/farmacología , Norepinefrina/metabolismo , Efectos Tardíos de la Exposición Prenatal , Serotonina/metabolismo , Animales , Encéfalo/crecimiento & desarrollo , Encéfalo/metabolismo , Femenino , Lóbulo Frontal/efectos de los fármacos , Hipocampo/efectos de los fármacos , Masculino , Embarazo , Ratas , Ratas Sprague-Dawley , Factores SexualesRESUMEN
Rats were sensitized to cocaine (15 mg/kg, i.p.) by 6 daily injections followed by a 48 h withdrawal prior to cocaine challenge. Involvement of excitatory amino acids in behavioral sensitization was assessed by comparing extracellular levels of aspartate and glutamate in the core of the nucleus accumbens in response to the first cocaine injection and the final cocaine challenge. Intracerebral microdialysis of the nucleus accumbens in freely moving awake rats allowed the comparison of behavioral state with extracellular aspartate and glutamate concentrations. Increased nucleus accumbens extracellular concentration of aspartate, but not glutamate, was observed in rats exhibiting behavioral sensitization to cocaine.
Asunto(s)
Ácido Aspártico/análisis , Cocaína/farmacología , Núcleo Accumbens/efectos de los fármacos , Animales , Conducta Animal/efectos de los fármacos , Ácido Glutámico/análisis , Masculino , Microdiálisis , Núcleo Accumbens/química , Ratas , Ratas Sprague-DawleyRESUMEN
The developmental and behavioral effects of prenatal exposure to cocaine and/or ethanol were examined in rats. Pregnant rats received ethanol (E; 2 g/kg, b.i.d.) orally, cocaine (C; 6 mg/kg/day, IV), or both (C/E) on gestational days 8-20. Controls consisted of pair-fed (PF) and untreated (UNT) groups. Offspring were weighed and examined for developmental markers beginning postnatal day one (PD1). On PD21 pups were individually observed in an open-field following either an injection of cocaine (10 mg/kg, IP), an injection of saline, or no treatment. Drug-treated and PF dams ate less food and gained less weight than the UNT dams. C and E litters had slightly increased mortality rates. Pups from both the C and E groups appeared less sensitive to the locomotor stimulant effect of cocaine. Pups from the E group engaged in significantly less spontaneous stereotypic locomotion than UNT and PF pups, while male pups from the C group exhibited a decrease in spontaneous exploratory behavior. Thus, prenatal exposure to C or E altered spontaneous and/or cocaine-induced behavior in weanling-aged rats, while the C/E combination did not augment either effect.
Asunto(s)
Conducta Animal/efectos de los fármacos , Depresores del Sistema Nervioso Central/toxicidad , Cocaína/farmacología , Cocaína/toxicidad , Etanol/toxicidad , Efectos Tardíos de la Exposición Prenatal , Animales , Ingestión de Líquidos/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Conducta Exploratoria/efectos de los fármacos , Femenino , Tamaño de la Camada/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Embarazo , Ratas , Ratas Sprague-Dawley , Conducta Estereotipada/efectos de los fármacos , Aumento de Peso/efectos de los fármacosRESUMEN
The effects of 1,1,1-trichloroethane (TCE) on physical and behavioral development were examined in CD-1 mice prenatally exposed under two regimens. In the first study, pregnant mice were exposed to either 2,000 ppm TCE or filtered air for 17 hrs. during gestational days (GD) 12-17. A third group remained untreated. The results revealed no differences on pregnancy outcome. TCE-exposed pups gained less weight, exhibited delays in developmental landmarks and acquisition of the righting reflex, had poorer performance on tests of motor coordination and exhibited delays in negative geotaxis relative to sham or untreated pups. A second experiment was designed to more closely parallel the intermittent, acute, high-concentration pattern of solvent abuse. Pregnant mice were exposed for 60 min. to 8,000 ppm TCE or sham placement in exposure chambers three times/day during GD's 12-17. The results were very similar to what were obtained in the more continuous exposure study. TCE-exposed pups gained less weight, had delays in developmental landmarks and acquisition of the righting reflex and exhibited weaker grip strength, poorer negative geotaxis and less rooting intensity in comparison to sham pups. These data provide evidence for the behavioral and developmental teratogenicity of prenatal TCE exposure late in gestation.
Asunto(s)
Sistema Nervioso/crecimiento & desarrollo , Efectos Tardíos de la Exposición Prenatal , Solventes/toxicidad , Tricloroetanos/toxicidad , Animales , Reacción de Prevención/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Edad Gestacional , Masculino , Ratones , Ratones Endogámicos , Actividad Motora/efectos de los fármacos , Sistema Nervioso/efectos de los fármacos , Equilibrio Postural/efectos de los fármacos , Embarazo , Desempeño Psicomotor/efectos de los fármacos , Reflejo/efectos de los fármacos , Solventes/administración & dosificación , Solventes/química , Trastornos Relacionados con Sustancias/psicología , Tricloroetanos/administración & dosificación , Tricloroetanos/químicaRESUMEN
On postnatal day 4, rats exposed to methadone prenatally but fostered to control dams, as well as those fostered to dams treated with methadone, exhibited significant reductions in striatal acetylcholine (ACh) content. This suggests that neonatal withdrawal from methadone is not responsible for the effects of prenatal exposure on cholinergic development in the early perinatal period. The effects of perinatal exposure to methadone on serotonin (5HT) and dopamine (DA) metabolism do not appear to be strictly related to changes in ACh content. Although prenatal exposure reduces 5-hydroxyindole acetic acid (5HIAA) content, changes in 5HT content prevent significant changes in the ratio 5HIAA/5HT. Pups exposed to methadone only prenatally (withdrawal group) exhibited a decreased DOPAC/DA ratio, whereas pups in the treatment group exposed to methadone both pre- and postnatally exhibited an increased DOPAC/DA ratio.
Asunto(s)
Metadona/farmacología , Narcóticos/farmacología , Neostriado/citología , Neuronas/metabolismo , Sistema Nervioso Parasimpático/citología , Efectos Tardíos de la Exposición Prenatal , Ácido 3,4-Dihidroxifenilacético/metabolismo , Acetilcolina/metabolismo , Animales , Dopamina/metabolismo , Femenino , Ácido Hidroxiindolacético/metabolismo , Masculino , Neostriado/efectos de los fármacos , Neostriado/metabolismo , Neuronas/efectos de los fármacos , Sistema Nervioso Parasimpático/efectos de los fármacos , Sistema Nervioso Parasimpático/metabolismo , Embarazo , Ratas , Ratas Sprague-Dawley , Serotonina/metabolismoRESUMEN
Pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that the following prenatal/postnatal exposure groups were obtained: water/water, methadone/water, water/methadone and methadone/methadone. Methadone slightly reduced litter size, particularly the number of male offspring, and reduced litter birth weight. The induction or maintenance of physical dependence in the postnatal methadone exposure groups was confirmed by an experiment in which PD19 pups were challenged with naloxone (1 mg/kg, s.c.). Methadone concentrations were assayed in pup brain on postnatal days 4, 10 and 22. Postnatal exposure to methadone via maternal milk produced measurable levels of methadone which decreased with age. Neuromuscular and physical development were assessed. Exposure to methadone accelerated acquisition of the righting reflex, but tended to delay the acquisition of the negative geotaxic response. Postnatal exposure to methadone was associated with decreased somatic growth as measured through postnatal day 21. The older pups (postnatal day 21) exposed to methadone exhibited variations in activity levels: pups exposed to methadone both prenatally and postnatally exhibited the least amount of spontaneous locomotor activity and pups exposed only postnatally exhibited the most activity. Therefore, it is possible to induce and/or maintain physical dependence via lactation in rat pups fostered to methadone-treated dams. Perinatal exposure to methadone by this route produces several subtle disruptions of pup development in the absence of gross maternal or fetal toxicity.
Asunto(s)
Conducta Animal/efectos de los fármacos , Metadona/farmacología , Efectos Tardíos de la Exposición Prenatal , Trastornos Relacionados con Sustancias , Análisis de Varianza , Animales , Peso Corporal/efectos de los fármacos , Ingestión de Líquidos/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Femenino , Masculino , Embarazo , RatasRESUMEN
Pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (initial dose, 9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that they were exposed to methadone prenatally and/or postnatally. Perinatal methadone exposure disrupted cholinergic activity on postnatal day 21 as measured by the turnover rate of acetylcholine (TRACh) in both female and male rats, although there were some sexually-dimorphic responses. The most profoundly affected brain region was the striatum, where prenatal exposure to methadone increased ACh turnover, whether or not the rats continued to be exposed to methadone postnatally. It appears unlikely that neonatal withdrawal contributes to brain regional changes in ACh turnover, as continued postnatal exposure to methadone did not prevent the prenatal methadone induced changes.
Asunto(s)
Acetilcolina/metabolismo , Encéfalo/efectos de los fármacos , Metadona/farmacología , Narcóticos/farmacología , Efectos Tardíos de la Exposición Prenatal , Receptores Colinérgicos/efectos de los fármacos , Animales , Animales Recién Nacidos , Encéfalo/fisiopatología , Mapeo Encefálico , Femenino , Humanos , Recién Nacido , Masculino , Síndrome de Abstinencia Neonatal/fisiopatología , Embarazo , Ratas , Receptores Colinérgicos/fisiología , DesteteRESUMEN
Intracerebral microdialysis was used to assess the effects of cocaine-HCl on extracellular concentrations of the excitatory amino acids aspartate and glutamate in the nucleus accumbens of awake, freely moving rats. After an initial equilibration period, cocaine (7.5, 15 or 30 mg/kg) or saline was injected i.p., and samples were collected for an additional 2 h. The highest dose of cocaine (30 mg/kg, i.p.) caused a 4-fold increase in glutamate levels and an 18-fold increase in aspartate levels over baseline. To verify that the source of the extracellular aspartate and glutamate was neuronal, additional experiments were conducted using Ca(2+)-free microdialysis buffer, and buffer containing 10 microM tetrodotoxin. Local perfusion with Ca(2+)-free buffer reduced the increase of extracellular aspartate and glutamate in rats injected with 30 mg/kg cocaine. Tetrodotoxin significantly decreased the cocaine-induced increase in excitatory amino acids, but not the behavioral response.
Asunto(s)
Ácido Aspártico/metabolismo , Cocaína/farmacología , Ácido Glutámico/metabolismo , Narcóticos/farmacología , Núcleo Accumbens/química , Análisis de Varianza , Animales , Ácido Aspártico/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Calcio/farmacología , Relación Dosis-Respuesta a Droga , Ácido Glutámico/efectos de los fármacos , Masculino , Microdiálisis , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/metabolismo , Ratas , Ratas Sprague-Dawley , Bloqueadores de los Canales de Sodio , Tetrodotoxina/farmacologíaRESUMEN
The effects of cocaine and the cocaine analog methyl-3-beta-(p-fluorophenyl)-1 alpha H, 5 alpha H-tropane-2b-carboxylate (CFT) on glutamate turnover rate were studied in the nucleus accumbens, striatum, frontal cortex, and parietal-cingulate cortex of the rat, using neurotransmitter turnover rate as an estimate of the activity of the glutamatergic neurons. Both cocaine [15 or 30 mg/kg, intraperitoneally (IP)] and CFT (2.2 mg/kg, IP) increased glutamate turnover in the nucleus accumbens, although the time course of their actions differed. These effects on glutamate turnover appeared at times after maximal motor activation of the animals had occurred. On the other hand, neither cocaine nor CFT affected glutamate turnover in the frontal cortex, parietal-cingulate cortex, or striatum. Neither cocaine nor CFT affected the content of glutamate or glucose in any brain region studied. Thus, although cocaine and CFT affect glutamatergic neurons in the CNS, these actions are not generalized across the CNS, but are restricted to a specific brain region.
Asunto(s)
Corteza Cerebral/efectos de los fármacos , Cocaína/análogos & derivados , Cocaína/farmacología , Cuerpo Estriado/efectos de los fármacos , Ácido Glutámico/metabolismo , Núcleo Accumbens/efectos de los fármacos , Análisis de Varianza , Animales , Corteza Cerebral/citología , Corteza Cerebral/metabolismo , Cuerpo Estriado/citología , Cuerpo Estriado/metabolismo , Relación Dosis-Respuesta a Droga , Masculino , Actividad Motora/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Núcleo Accumbens/citología , Núcleo Accumbens/metabolismo , Ratas , Ratas Sprague-Dawley , Estimulación QuímicaRESUMEN
Amphetamine (which enhances dopaminergic, cholinergic, and glutamatergic activity) increases release of ascorbic acid (AA) and uric acid (UA) in the caudate nucleus. In this study, linear sweep voltammetry with carbon past electrodes was used to investigate the effects of haloperidol (a DA receptor blocker), scopolamine (a muscarinic receptor blocker), and MK-801 (an NMDA receptor blocker) alone and in combination on amphetamine-induced increases in AA and UA in the caudate nucleus. Both scopolamine (0.5 mg/kg, IP) and MK-801 (0.5 mg/kg, IP) significantly reduced amphetamine-induced increases in AA. Also, scopolamine did not affect MK-801-induced reductions of amphetamine-induced increases in AA. Unexpectedly, a subthreshold dose of haloperidol (0.1 mg/kg, IP) potentiated the ability of scopolamine to block amphetamine-induced increases in AA. Therefore, the data suggest that acetylcholine release and subsequent binding to cholinergic receptors in the caudate, are components of amphetamine-induced increases in AA. In addition, scopolamine modulated haloperidol-induced reductions of amphetamine-induced increases in release of UA. Thus, our data demonstrate that cholinergic and dopaminergic systems may interact to control release of UA.
Asunto(s)
Anfetamina/farmacología , Ácido Ascórbico/sangre , Maleato de Dizocilpina/farmacología , Haloperidol/farmacología , Escopolamina/farmacología , Ácido Úrico/sangre , Animales , Núcleo Caudado/efectos de los fármacos , Núcleo Caudado/metabolismo , Relación Dosis-Respuesta a Droga , Electrodos , Masculino , Ratas , Ratas WistarRESUMEN
Pregnant rats were injected with cocaine (CN; 6 mg/kg) or an equal volume of saline (SAL), via the tail vein, on gestation days 8-20. A third group was untreated (UT). Maternal weight gain was not affected by dam treatment despite slight differences in food intake. Litter characteristics (e.g., litter size, pup weight) did not differ among groups. Indices of fetal mortality were not affected by the treatments. Developmental tests, initiated on postnatal day (PND) 2, indicated slight delays in the negative geotaxic response and eye opening in cocaine-exposed pups. Open-field and tail-flick tests were performed on PND 21. Pups were acutely injected with cocaine (10 mg/kg, IP), saline, or received no treatment before placement in a novel open field; morphine (1.5 mg/kg, SC) or saline was injected prior to the tail flick test. Pups from CN dams exhibited a significant decrease in spontaneous exploratory behavior compared to both controls, and a time-dependent increase in rearing compared to pups from UT dams. The acute cocaine injection prior to placement in the open field did not alter locomotion or rearing among dam treatment groups. However, the acute cocaine injection did increase stereotypy ratings for female pups from CN dams compared to similarly treated males, and females from SAL and UT dams. No differences were observed among groups in the tail-flick test. These data suggest that the IV route of administration provides a viable method of cocaine delivery in pregnant rats, and provides further evidence of the developmental and behavioral teratogenicity of prenatal cocaine exposure.
Asunto(s)
Conducta Animal/efectos de los fármacos , Cocaína/toxicidad , Efectos Tardíos de la Exposición Prenatal , Animales , Peso al Nacer/efectos de los fármacos , Cocaína/administración & dosificación , Ingestión de Líquidos/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Conducta Exploratoria/efectos de los fármacos , Femenino , Inyecciones Intravenosas , Masculino , Morfina/farmacología , Actividad Motora/efectos de los fármacos , Nociceptores/efectos de los fármacos , Dimensión del Dolor/efectos de los fármacos , Embarazo , Ratas , Ratas Sprague-Dawley , Reflejo/efectos de los fármacos , Conducta Estereotipada/efectos de los fármacos , Aumento de Peso/efectos de los fármacosRESUMEN
Rats running in a runway emit discriminable odors when encountering reward (R) or nonreward (N) goal events, and subsequent rats use these odors as discriminative stimuli to alter their approach speeds. In the present studies, a third goal event, aversively conditioned denatonium saccharide (A), was introduced. In Experiment 1, rats evidently emitted an odor when encountering the A goal event, because in the presence of this A odor subsequent conspecifics slowed their approach to the goal, much like their behavior on N trials. In Experiment 2, when N odor signaled R goal events and A odor signaled A goal events, rats approached quickly to N but slowly to A, indicating that they could discriminate N and A odors at the given concentrations. These studies indicate that rats emit an odor when confronted with a signal of impending illness and that this odor seems readily discriminable from R and N odors.
Asunto(s)
Comunicación Animal , Nivel de Alerta , Reacción de Prevención , Condicionamiento Clásico , Odorantes , Gusto , Animales , Conducta Apetitiva , Aprendizaje Discriminativo , Masculino , Motivación , Actividad Motora , Ratas , Ratas EndogámicasRESUMEN
Linear sweep voltammetry was used to investigate the effects of amphetamine (which enhances the release of dopamine) and/or pilocarpine (a cholinergic agonist) on the release of ascorbic acid and uric acid in brain areas differing in dopamine and acetylcholine concentrations. In caudate, nucleus accumbens, and hippocampus, the magnitude of the amphetamine-induced increase in ascorbic acid was roughly correlated with dopamine content of the brain area tested. Cingulate cortex was a notable exception; the increase in ascorbic acid was greater than that in nucleus accumbens. Pilocarpine produced the greatest increase in ascorbic acid in cingulate cortex, even though cingulate cortex has the lowest acetylcholine concentration of the brain areas tested. Except for cingulate cortex, the ascorbic acid data were consistent with the hypothesis that amphetamine and pilocarpine release different pools of ascorbic acid. The uric acid data were consistent with the hypothesis that amphetamine and pilocarpine release the same pool of uric acid. The unexpected findings in cingulate cortex may point to an important role of ascorbic acid in this brain area.
Asunto(s)
Anfetamina/farmacología , Ácido Ascórbico/metabolismo , Encéfalo/efectos de los fármacos , Pilocarpina/farmacología , Ácido Úrico/metabolismo , Animales , Encéfalo/metabolismo , Interacciones Farmacológicas , Masculino , Ratas , Ratas EndogámicasRESUMEN
Gamma (gamma) is a recently proposed statistic that quantifies and describes the repetitive patterns of locomotion (locomotor stereotypy) exhibited by amphetamine-treated rats in an open field. The time-course of locomotor stereotypy after 1, 2, 3, and 4 mg/kg amphetamine was investigated in this research. Locomotor stereotypy was often evident during the first observation period after amphetamine. Lower doses of amphetamine produced qualitatively different locomotor stereotypy than higher doses. Rats given higher doses of amphetamine exhibited locomotor stereotypy during the "hyperactivity" phase of the three-phase response produced by higher doses of amphetamine (hyperactivity; absence of locomotions, increased sniffing, biting etc.; hyperactivity). Contrary to expectations, rats injected with 2 mg/kg amphetamine exhibited the highest and most sustained increase in gamma. We conclude that locomotor stereotypy is an important component of the behavioral effects of amphetamine in rats. Whether locomotor stereotypy and focused stereotypy are similar phenomena is still unclear.