Participação de receptores GABA B na modulação do consumo etílico em ratos Wistar / Involvement of GABA B receptor on ethylic consumption modulation in Wistar rats

Introdução: o baclofeno, uma droga agonista seletivo de GABA B, tem sido apontado como uma nova opção de tratamento do etilismo. Neste estudo avaliou-se o efeito do baclofeno no consumo etílico em ratos Wistar. Materiais e Métodos: o experimento ocorreu em quatro fases: exposição, abstinência, reexposição e tratamento. Os animais foram alocados em grupos: 1, 2, 3 e 4 (n=5 por grupo), expostos à água pura, solução hidroalcoólica (SHA) 5% e SHA 10%; grupo 5 (subdividido em A, B e C N =5 por subgrupo) e grupo 6 (n=5), ambos expostos a apenas água pura. A administração de baclofeno via intraperitoneal destinou aos grupos 1, 2, 3 e 5 em diferentes doses. Nos demais grupos, administrou-se placebo. Aferiu-se o consumo das soluções em todas as fases, para fins comparativos. Resultados: o baclofeno, na dose de 1mg/Kg, reduziu o consumo de SHA 10% no grupo 1, que apresentou maior consumo etílico durante o experimento. Os demais grupos apresentaram menor consumo das SHA ofertadas, sem redução da ingesta etílica após administração da droga nas doses de 2 e 3mg/Kg. Conclusão: baclofeno reduziu etilismo apenas em animais com maior consumo etílico prévio à sua administração. O peso dos animais não foi fator determinante na resposta à droga. A dose efetiva no tratamento dos efeitos da privação alcoólica foi a de menor concentração (1mg/kg).

Introduction: Baclofen, a GABA B agonist, has been pointed as a new drug on the alcohol consumption treatment. This study has evaluated baclofen ́s effect on ethanol consumption in Wistar rats. Materials and Methods: four phases protocol: exposure, abstinence, re-exposure and treatment. Animals were allocated into groups: 1, 2, 3 and 4 (n=5 per group), exposed to pure water, 5% ethanol solution and 10% ethanol solution. Group 5 (subdivided into A, B and C, n=5 by subgroup) and group 6 (n=5), exposed to pure water. Baclofen intraperitoneal administration was destined to groups 1, 2, 3 and 5 (A, B and C) in different doses. The remaining groups received saline solution as control. Solutions consumption was assessed in all phases for comparative purposes. Results: Baclofen at 1mg/Kg reduced the 10% (vv) water-alcohol consumption in animals from Group 1, which also presented greater ethanol consumption during the experiment. The other groups showed a lower water - alcohol consumption and did not show an ethanol intake reduction after the drug administration in both 2 and 3mg/Kg doses. Conclusion: Baclofen only reduces alcoholism in animals with higher ethanol consumption. Animals weight is not a determining factor in ethanol consumption or in baclofen response. The effective baclofen dose in treating the deprivation alcohol effects was observed in the lowest concentration, corresponding to 1mg/Kg dose.

Antinociceptive effect of aqueous extract of Origanum vulgare L. in male rats: possible involvement of the GABAergic system

The objective of the present investigation was to assess the possible involvement of GABAergic mechanism in analgesic effect of aqueous extract of Origanum Vulgare [ORG] in a rat model of acute pain test. Sixty-three anaesthetized male Wistar rats [200-250 g] were cannulated into the left ventricle. Five to seven days after the recovery from surgery, ORG extract was intraventricularly injected at dose of 3 ?g/rat i.c.v. Then, baclofen [10 mg/Kg, IP], CGP35348 [100 nmol/Kg, i.c.v], muscimol [1 mg/Kg IP] and bicuculline [5 mg/Kg IP] were separately injected 20 min before the injection of ORG. The experimental groups were compared with intact [control] group [n = 7]. The response latency of rats to thermal stimulation was recorded using Tail-Flick test. Injection of ORG extract resulted in a significant and dose-dependent increase in the response latency. There was also a significant increase in the response latency after co-administration of ORG extract with baclofen when compared with control group. However, following co-administration of ORG extract/bicuculline, a significant decrease in the response latency was observed compared to control group. In conclusion, the results of the present study suggest that aqueous extract of Origanum vulgare L. ssp. viridis possesses antinociceptive activity in a dose-dependent manner and ORG-induced antinociception might be mediated, at least in part, by both GABA receptors

GABA B mediated analgesia in tonic pain in monkeys.

The present study was designed to characterise the analgesia produced by the GABA B agonist baclofen in tonic pain in monkeys. The effect of various doses of baclofen was studied on formalin induced pain. Baclofen was injected intraperitoneally 30 min prior to formalin injection in five doses of 2, 4, 6, 8, and 10 mg/kg and the pain was quantified for a period of one hour. Baclofen produced dose related analgesia, 6 mg/kg having maximal effect. The antinociceptive effect of baclofen could be attributed to the effect of baclofen on GABA B receptors producing presynaptic inhibition of primary nociceptive afferents in the dorsal horn of the spinal cord.