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1.
Headache ; 59(7): 1080-1083, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31257584

RESUMO

BACKGROUND AND OBJECTIVE: Sodium divalproate is an effective neuromodulator for migraine prevention. Recommended doses vary from 1,000 to 1,500 mg/day, which may provoke unpleasant side effects as weight gain, tremor, and hair loss. Some patients do respond to lower doses even used once daily in ER presentations, but alternating low daily doses was never studied so far. The aim of this study was to evaluate the adherence, the tolerability, and the efficacy of sodium divalproate (SD) in low alternating daily doses for migraine prevention in patients of a tertiary center. METHODS: Consecutive migraineurs from a tertiary center to whom SD was prescribed as monotherapy from January 2017 until September 2018 were studied retrospectively. The doses were 250 mg alternated with 500 mg and were used based on the treating physician expertise and previous experience with tolerability issues when using higher doses. Headache frequency compared to baseline, adherence expressed by returning to a visit after 2 and 4 months and side effects reported by the patients, were evaluated. RESULTS: Sixty-eight patients (53 women and 15 men, aged 18-58) were included. The average headache frequency (HF) during baseline was decreased from 8.2 to 5.1 headache days/month among the 50 out of 68 patients returning at 2 months (adherence rate 73.5%). Weight gain was reported by 15 patients (30%, mean 2.1 kg). At 4 months, HF was reduced to 4.2 days/month (adherence rate 61.8%, n = 42) and weight gain reported by 18 patients (42.8%, mean 2.3 kg). CONCLUSIONS: Despite the retrospective open design, which cannot allow definitive conclusions, SD in low alternating daily doses seems to be effective as with higher doses, but still induce modest weight gain. Controlled studies are necessary to confirm these observations.


Assuntos
GABAérgicos/administração & dosagem , Transtornos de Enxaqueca/prevenção & controle , Ácido Valproico/administração & dosagem , Adolescente , Adulto , Feminino , GABAérgicos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Ácido Valproico/efeitos adversos , Adulto Jovem
2.
J Clin Psychopharmacol ; 37(1): 54-60, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27930500

RESUMO

BACKGROUND: Posttraumatic stress disorder (PTSD) is one of the chronic and disabling psychiatric disorders, particularly in combat veterans. In a case series, rivastigmine was suggested to be an effective augmentation in treatment of PTSD. The aim of the present study was to evaluate this finding in a randomized controlled trial. METHOD: A 12-week, double-blind, placebo-controlled clinical trial was performed on 36 male patients (aged 42-60 years) diagnosed with chronic, combat-related PTSD. Subjects were screened for apparent cognitive deficits by means of Mini-Mental State Examination. All patients received selective serotonin reuptake inhibitors plus sodium valproate for 4 weeks and then reevaluated. Subjects who did not show adequate response were randomly assigned into 3 groups receiving rivastigmine (up to 6 mg/d), placebo, or the prior treatment regimen. Efficacy of medication was measured by administering PTSD Check List-Military Version at baseline and weeks 2, 4, 8, and 12. Collected data were analyzed by analysis of variance and repeated measurement. Reported differences were considered significant at the level of 0.05 or less. RESULTS: The 3 groups showed statistically significant reductions in the total PTSD Check List-Military Version, avoidance subscale, and the reexperience subscale but not in the hyperarousal subscale. No significant differences were found between the 3 groups. CONCLUSIONS: In contrast to the previous case series, findings of the current study did not support the efficacy of adjunctive rivastigmine in treatment of PTSD. This hypothetically could be due to the fact that all the study's subjects scored higher than 25 on Mini-Mental State Examination.


Assuntos
Inibidores da Colinesterase/farmacologia , Distúrbios de Guerra/tratamento farmacológico , GABAérgicos/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Rivastigmina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Ácido Valproico/farmacologia , Adulto , Inibidores da Colinesterase/administração & dosagem , Doença Crônica , Método Duplo-Cego , Sinergismo Farmacológico , GABAérgicos/administração & dosagem , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Rivastigmina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Ácido Valproico/administração & dosagem
3.
Brain Res ; 1644: 258-66, 2016 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-27208494

RESUMO

Through GABAergic fibers, globus pallidus (GP) coordinates basal ganglia global function. Electrical activity of GP neurons depends on their membrane properties and afferent fibers, including GABAergic fibers from striatum. In pathological conditions, abnormal electrical activity of GP neurons is associated with motor deficits. There is a GABAergic pathway from the GP to the reticular thalamic nucleus (RTn) whose contribution to RTn neurons electrical activity has received little attention. This fact called our attention because the RTn controls the overall information flow of thalamic nuclei to cerebral cortex. Here, we study the spontaneous electrical activity of RTn neurons recorded in vivo in anesthetized rats and under pharmacological activation or inhibition of the GP. We found that activation of GP predominantly diminishes the spontaneous RTn neurons firing rate and its inhibition increases their firing rate; however, both activation and inhibition of GP did not modified the burst index (BI) or the coefficient of variation (CV) of RTn neurons. Moreover, stimulation of striatum predominantly diminishes the spiking rate of GP cells and increases the spiking rate in RTn neurons without modifying the BI or CV in reticular neurons. Our data suggest a GP tight control over RTn spiking activity.


Assuntos
Potenciais de Ação , Corpo Estriado/fisiologia , Globo Pálido/fisiologia , Neurônios/fisiologia , Núcleos Talâmicos/fisiologia , Animais , Corpo Estriado/efeitos dos fármacos , Agonistas de Aminoácidos Excitatórios/administração & dosagem , GABAérgicos/administração & dosagem , Globo Pálido/efeitos dos fármacos , Ácido Glutâmico/administração & dosagem , Masculino , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiologia , Neurônios/efeitos dos fármacos , Ratos , Ratos Wistar , Núcleos Talâmicos/efeitos dos fármacos , Ácido gama-Aminobutírico/administração & dosagem
4.
Brain Res Bull ; 124: 103-15, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27063286

RESUMO

The abnormal firing of damaged primary afferents and the changes in the central nervous system (CNS) play important role in the initiation and maintenance phases of neuropathic pain. These phases of neuropathic pain involve changes in the GABAergic control of descending pathways that travel through the dorsolateral funiculus (DLF). The present study shows that unilateral DLF lesion increased the antiallodynic effect of muscimol (0.2µg/5µL) (a GABAA receptor agonist) in the initiation, but not maintenance phase of the mechanical allodynia induced by a spinal nerve ligation (SNL) of the ipsilateral hindpaw of rats. The unilateral DLF lesion increased the antiallodynic effect of baclofen (0.8µg/5µL) (a GABAB receptor agonist) in the initiation phase and reduced your effect in the maintenance phase of the mechanical allodynia induced by a spinal nerve ligation (SNL) of the ipsilateral paw of rats. The unilateral DLF lesion significantly reduced the proallodynic effect of an intrathecal injection of phaclofen (30µg/5µL) (a GABAB receptor antagonist), but not bicuculline (0.3µg/5µL) (a GABAA receptor antagonist). The effect of DLF lesion on the proallodynic effect of phaclofen was observed in the maintenance, but not in the initiation phase of the mechanical allodynia induced by SNL. We than conclude that the spinal GABAergic neurotransmission is negatively modulated by DLF using GABAA and GABAB receptors, in the initiation phase of mechanical allodynia induced by SNL. In addition, the integrity of DLF is necessary for the effectiveness of GABAergic transmission that occurs via spinal GABAB, but not GABAA receptors, in the maintenance phase of mechanical allodynia induced by SNL.


Assuntos
Baclofeno/análogos & derivados , GABAérgicos/administração & dosagem , Muscimol/administração & dosagem , Neuralgia , Corno Dorsal da Medula Espinal/patologia , Nervos Espinhais/lesões , Animais , Baclofeno/administração & dosagem , Bicuculina/administração & dosagem , Lateralidade Funcional , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Injeções Espinhais , Ligadura/efeitos adversos , Masculino , Neuralgia/complicações , Neuralgia/tratamento farmacológico , Neuralgia/etiologia , Medição da Dor , Limiar da Dor/efeitos dos fármacos , Estimulação Física , Ratos , Ratos Wistar , Corno Dorsal da Medula Espinal/efeitos dos fármacos , Estatísticas não Paramétricas
5.
Neuroscience ; 285: 60-9, 2015 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-25446344

RESUMO

Liposomes are nanosystems that allow a sustained release of entrapped substances. Gamma-aminobutyric acid (GABA) is the most prevalent inhibitory neurotransmitter of the central nervous system (CNS). We developed a liposomal formulation of GABA for application in long-term CNS functional studies. Two days after liposome-entrapped GABA was injected intracerebroventricularly (ICV), Wistar rats were submitted to the following evaluations: (1) changes in mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) to ICV injection of bicuculline methiodide (BMI) in anesthetized rats; (2) changes in cardiovascular reactivity to air jet stress in conscious rats; and (3) anxiety-like behavior in conscious rats. GABA and saline-containing pegylated liposomes were prepared with a mean diameter of 200 nm. Rats with implanted cannulas targeted to lateral cerebral ventricle (n = 5-8/group) received either GABA solution (GS), empty liposomes (EL) or GABA-containing liposomes (GL). Following (48 h) central microinjection (2 µL, 0.09 M and 99 g/L) of liposomes, animals were submitted to the different protocols. Animals that received GL demonstrated attenuated response of RSNA to BMI microinjection (GS 48 ± 9, EL 43 ± 9, GL 11 ± 8%; P < 0.05), blunted tachycardia in the stress trial (ΔHR: GS 115 ± 14, EL 117 ± 10, GL 74 ± 9 bpm; P<0.05) and spent more time in the open arms of elevated plus maze (EL 6 ± 2 vs. GL 18 ± 5%; P = 0.028) compared with GS and EL groups. These results indicate that liposome-entrapped GABA can be a potential tool for exploring the chronic effects of GABA in specific regions and pathways of the central nervous system.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Fármacos do Sistema Nervoso Central/administração & dosagem , GABAérgicos/administração & dosagem , Lipossomos/administração & dosagem , Ácido gama-Aminobutírico/administração & dosagem , Animais , Ansiedade/tratamento farmacológico , Ansiedade/fisiopatologia , Pressão Arterial/efeitos dos fármacos , Bicuculina/administração & dosagem , Bicuculina/análogos & derivados , Cateteres de Demora , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Frequência Cardíaca/efeitos dos fármacos , Infusões Intraventriculares , Rim/inervação , Masculino , Microinjeções , Ratos Wistar , Estresse Fisiológico/efeitos dos fármacos , Estresse Fisiológico/fisiologia , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiologia , Taquicardia/tratamento farmacológico , Taquicardia/fisiopatologia
6.
Photochem Photobiol Sci ; 12(9): 1565-70, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23674097

RESUMO

We have devised a new caged GABA based on ruthenium bipyridyl coordination chemistry. This phototrigger delivers GABA upon irradiation with wavelengths up to 532 nm undergoing heterolytic photocleavage, in a clean and very fast (a few nanoseconds) photoreaction. With an absorptivity coefficient ε(MAX) = 5300 M(-1) cm(-1) at 447 nm and a quantum efficiency φ ~ 0.09, RuBiGABA-2 is among the most active caged-GABAs, especially at long wavelengths. This highly hydrophilic caged GABA can be synthesized in a simple one-pot reaction. The synthesis, chemical characterization and photochemical properties are presented. Finally, the usefulness of this caged compound is demonstrated by photodelivering free GABA on leech motoneurons.


Assuntos
2,2'-Dipiridil/análogos & derivados , GABAérgicos/administração & dosagem , Compostos Organometálicos/química , Fosfinas/química , Ácido gama-Aminobutírico/administração & dosagem , 2,2'-Dipiridil/química , Animais , GABAérgicos/química , GABAérgicos/farmacologia , Gânglios/citologia , Gânglios/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas , Sanguessugas/citologia , Sanguessugas/efeitos dos fármacos , Luz , Fotólise , Ácido gama-Aminobutírico/análogos & derivados , Ácido gama-Aminobutírico/farmacologia
7.
Behav Brain Res ; 232(1): 60-5, 2012 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-22483998

RESUMO

GABAergic mechanisms in the preoptic region of the hypothalamus (POA) have been implicated in the generation and maintenance of NREM (quiet) sleep. We recently reported that neurons in the median peptic nucleus (MnPN) in the POA of the cat are selectively activated during NREM sleep. In the present study, we explored the hypothesis that NREM sleep is controlled by GABAergic mechanisms within the MnPN. Consequently, adult cats were utilized to determine GABA immunorreactivity within the MnPN and to examine the effects on sleep of the microinjection of a GABA(A) agonist (muscimol) and a GABA(A) antagonist (bicuculline) into this area. GABAergic neurons were present throughout the MnPN. Compared with control microinjections, after the application of muscimol, the time spent in NREM sleep (59.8±7.5 min) and REM sleep (6.9±4.7 min) decreased compared with control microinjections (103.8±5.2 and 20.2±4.3 min, respectively; P<0.005). In contrast, bicuculline microinjections increased only NREM sleep time (103.0±23.0 vs 77.7±23.7 min; P<0.05). These results demonstrate that GABAergic processes within the MnPN are involved in the generation and maintenance of sleep, especially NREM sleep.


Assuntos
GABAérgicos/farmacologia , Área Pré-Óptica/fisiologia , Sono/fisiologia , Ácido gama-Aminobutírico/fisiologia , Animais , Bicuculina/administração & dosagem , Bicuculina/farmacologia , Gatos , Interpretação Estatística de Dados , Eletroencefalografia/efeitos dos fármacos , Eletromiografia/efeitos dos fármacos , GABAérgicos/administração & dosagem , Agonistas GABAérgicos/administração & dosagem , Agonistas GABAérgicos/farmacologia , Antagonistas GABAérgicos/administração & dosagem , Antagonistas GABAérgicos/farmacologia , Neurônios GABAérgicos , Imuno-Histoquímica , Masculino , Microinjeções , Muscimol/administração & dosagem , Muscimol/farmacologia , Área Pré-Óptica/efeitos dos fármacos , Sono/efeitos dos fármacos , Sono REM/efeitos dos fármacos , Vigília/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismo
8.
Peptides ; 27(9): 2307-12, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16650508

RESUMO

Although the gastrin-releasing peptide receptor (GRPR) has recently emerged as a system importantly involved in regulating memory formation, the role of hippocampal GRPRs in memory remains controversial. The present study examined the effects of GRPR antagonism on memory consolidation in area CA1 of the hippocampus. Male Wistar rats received bilateral infusions of the GRPR antagonist [D-Tpi6, Leu13 psi(CH2NH)-Leu14] bombesin (6-14) (RC-3095; 1, 3, or 10 microg/side) into the dorsal hippocampus immediately after inhibitory avoidance (IA) training. RC-3095 at 1 microg impaired, whereas the dose of 10 microg enhanced, 24-h IA retention. A second experiment showed that the RC-3095-induced enhancement of memory consolidation was prevented by pretraining infusion of an otherwise ineffective dose of the gamma-aminobutyric acid type A (GABA(A)) receptor agonist muscimol. The results indicate that high doses of GRPR antagonists can induce enhancement of memory consolidation in the hippocampus. In addition, the memory-enhancing effect of GRPR antagonists might be mediated by inhibition of GABAergic transmission.


Assuntos
Bombesina/análogos & derivados , GABAérgicos/administração & dosagem , Hipocampo/efeitos dos fármacos , Memória/efeitos dos fármacos , Fragmentos de Peptídeos/administração & dosagem , Receptores da Bombesina/antagonistas & inibidores , Receptores de GABA-A/metabolismo , Animais , Bombesina/administração & dosagem , Bombesina/farmacologia , Relação Dose-Resposta a Droga , GABAérgicos/farmacologia , Agonistas de Receptores de GABA-A , Hipocampo/metabolismo , Masculino , Modelos Biológicos , Muscimol/farmacologia , Fragmentos de Peptídeos/farmacologia , Ratos , Receptores da Bombesina/metabolismo
9.
Medicina (B Aires) ; 60(2): 229-32, 2000.
Artigo em Espanhol | MEDLINE | ID: mdl-10962814

RESUMO

We evaluated, in immature female rats, the effect of the GABAergic system on the reproductive axis and on pubertal development. Initially, using a prolonged treatment with aminooxyacetic acid (AOAA), increasing hypothalamic GABA (p < 0.002), and decreasing GnRH and glutamate content (p < 0.05 and < 0.02). Treated rats showed diminished serum LH (p < 0.05) and estradiol (p < 0.005) levels. Vaginal opening occurred at 30.8 +/- 0.6 days in controls, and at 36.7 +/- 0.98 days in AOAA-treated rats. Acute treatment with AOAA resulted in a decreased GnRH and glutamate output, and in an increased taurine release from superfused hypothalamic fragments. This effect was mimicked by the GABA-A and GABA-B agonists. The activation of the GABAergic system during postnatal days 23-29 significantly restrains the hypothalamo-pituitary-ovaric axis and delays the onset of puberty. The existence of a physiological cross-talk between excitatory and inhibitory amino acid neurotransmitters regulating GnRH release during the onset of puberty is postulated.


Assuntos
Ácido Amino-Oxiacético/administração & dosagem , Animais Recém-Nascidos , GABAérgicos/administração & dosagem , Neurotransmissores/fisiologia , Ácido gama-Aminobutírico/efeitos dos fármacos , Animais , Estudos de Casos e Controles , Estradiol/sangue , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Ratos , Ratos Wistar , Taurina/metabolismo , Ácido gama-Aminobutírico/metabolismo
10.
Medicina [B.Aires] ; 60(2): 229-32, 2000. gra
Artigo em Espanhol | BINACIS | ID: bin-12486

RESUMO

Evaluamos 1) efecto del tratamiento prolongado (días 23-29 postnatales) con ácido aminooxiacético (AAOA) sobre el desarrollo puberal en ratas hembra; este tratamiento aumentó el contenido de GABA (p< 0.002), disminuyendo el de GnRH y glutamato (p < 0.05 y < 0.02) en hipotálamo. La LH (p < 0.05) y el estradiol (p < 0.005) séricos cayeron. La apertura vaginal fue a los 30.8 + 0.6 días en los controles, y a los 36.7 + 0.98 días en las tratadas (p < 0.0001). 2) A los 30 días, el tratamiento agudo con AAOA redujo la liberación ex vivo de GnRH y de glutamato la de taurina. Este efecto fue similar al observado agregando al medio agonistas GABA-A y B. Conclusiones: la activación peripuberal del sistema GABAérgico frena el eje reprodutor, produciendo un retraso en el desarrollo. Esto podría atribuirse a la existencia, en esta etapa, de interrelaciones fisiológicas entre los aminoácidos que regulan la secreción de GnRH (GABA, glutamato, taurina). (AU)


Assuntos
Animais , Feminino , Ratos , RESEARCH SUPPORT, NON-U.S. GOVT , Animais Recém-Nascidos , Neurotransmissores/fisiologia , Ácido gama-Aminobutírico/efeitos dos fármacos , Ácido Amino-Oxiacético/administração & dosagem , GABAérgicos/administração & dosagem , Ratos Wistar , Estudos de Casos e Controles , Ácido gama-Aminobutírico/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Taurina/metabolismo , Estradiol/sangue
11.
Medicina (B.Aires) ; Medicina (B.Aires);60(2): 229-32, 2000. graf
Artigo em Espanhol | LILACS | ID: lil-262217

RESUMO

Evaluamos 1) efecto del tratamiento prolongado (días 23-29 postnatales) con ácido aminooxiacético (AAOA) sobre el desarrollo puberal en ratas hembra; este tratamiento aumentó el contenido de GABA (p< 0.002), disminuyendo el de GnRH y glutamato (p < 0.05 y < 0.02) en hipotálamo. La LH (p < 0.05) y el estradiol (p < 0.005) séricos cayeron. La apertura vaginal fue a los 30.8 + 0.6 días en los controles, y a los 36.7 + 0.98 días en las tratadas (p < 0.0001). 2) A los 30 días, el tratamiento agudo con AAOA redujo la liberación ex vivo de GnRH y de glutamato la de taurina. Este efecto fue similar al observado agregando al medio agonistas GABA-A y B. Conclusiones: la activación peripuberal del sistema GABAérgico frena el eje reprodutor, produciendo un retraso en el desarrollo. Esto podría atribuirse a la existencia, en esta etapa, de interrelaciones fisiológicas entre los aminoácidos que regulan la secreción de GnRH (GABA, glutamato, taurina).


Assuntos
Animais , Feminino , Ratos , /fisiologia , Ácido Amino-Oxiacético/administração & dosagem , Animais Recém-Nascidos , GABAérgicos/administração & dosagem , Ácido gama-Aminobutírico/efeitos dos fármacos , Estudos de Casos e Controles , Estradiol/sangue , Ácido gama-Aminobutírico/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Ratos Wistar , Taurina/metabolismo
12.
Peptides ; 19(2): 383-8, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9493872

RESUMO

We have tried to investigate the possible interaction between the gabaergic system and alpha-MSH at a cellular level in an in vitro model of male albino rats tissue slices containing accumbens and caudate-putamen nuclei. Alpha-MSH alone increases cAMP levels, as does diazepam and phaclofen; however, these effects were blocked by SCH-23390. Both flumazenil and baclofen induced a decrease in the cAMP content. When both alpha-MSH and gabaergic agents were incubated together, cAMP levels were modified. It can be assumed that cAMP production by the neuropeptide and the gabaergic agents could be linked to the activation of dopaminergic D1 receptors. The latter receptors had no prominent effect on the interaction between alpha-MSH and the GABA agonists and antagonists. In summary, our results suggested that alpha-MSH and GABA system could be biochemically linked to produce a cellular effect.


Assuntos
Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , AMP Cíclico/metabolismo , GABAérgicos/administração & dosagem , alfa-MSH/administração & dosagem , Animais , Baclofeno/administração & dosagem , Baclofeno/análogos & derivados , Benzazepinas/administração & dosagem , Diazepam/administração & dosagem , Interações Medicamentosas , Flumazenil/administração & dosagem , Agonistas de Receptores de GABA-A , Antagonistas de Receptores de GABA-A , Agonistas dos Receptores de GABA-B , Antagonistas de Receptores de GABA-B , Técnicas In Vitro , Masculino , Modelos Neurológicos , Ratos , Ratos Wistar , Receptores de Dopamina D1/efeitos dos fármacos , Receptores de Dopamina D1/metabolismo
13.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;28(1): 88-99, Jan. 1995. graf
Artigo em Inglês | LILACS | ID: lil-153335

RESUMO

The interaction between GABAergic and dopaminergic system within the central nervous system was investigated in rats using the open-field apparatus and apomorphine-induced stereotypy, and in mice using haloperidol-induced catalepsy. The single intraperitoneal adminsitration of baclofen 3.0 mg/kg, 4,5,6,7-tetrahydroisoxasolo-(5,4-c) piridin-3-ol (THIP) 10.0 mg/kg and picrotoxin 2.0 mg/kg decreased both ambulation and rearing frequencies of the rats in the open-field; only the GABA agonists increased the duration of animal immobility. THIP (10.0 mg/kg) increased the duration of haloperidol-induced catalepsy. For apomorphine-induced stereotypy, baclofen 3.0 mg/kg and picrotoxin 1.0 mg/kg induced a significant leftward displacement of the control dose-response curve constructed for apomorphine (0.1-10 mg/kg) in relation to the control. In addition, baclofen, THIP, picrotoxin and 3-mercaptopropionic acid (3-MPA) 10.0 mg/kg decreased both rearing and sniffing behaviors elicited by apomorphine and increased licking and/ or gnawing. Different mechanisms seem to be involved in the similar effects induced by GABA agonists and antagonists. Picrotoxin induced stereotyped movements per se with a dose-dependent effect, but baclofen and THIP did not. The present data suggest that GABA manipulation facilitates the progressive activation of the different dopaminergic pathways involved in stereotyped behaviors, thus increasing those stereotyped components (gnawing and licking) that appear after a high level of activation of dopaminergic pathways


Assuntos
Animais , Masculino , Camundongos , Ratos , /farmacologia , GABAérgicos/farmacologia , Apomorfina/farmacologia , Baclofeno/farmacologia , Catalepsia/induzido quimicamente , Haloperidol/farmacologia , Picrotoxina/farmacologia , Comportamento Estereotipado/efeitos dos fármacos , /administração & dosagem , GABAérgicos/administração & dosagem , Apomorfina/administração & dosagem , Baclofeno/administração & dosagem , Haloperidol/administração & dosagem , Atividade Motora/efeitos dos fármacos , Picrotoxina/administração & dosagem , Ratos Wistar
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