| Abstrakt: |
Aims: Recent studies have shown that Hypericum perforatum extracts (HPE) inhibit ethanol intake in alcohol-preferring rats, but their mechanism of action is still unknown. HPE have been shown to bind at γ-aminobutyric acid (GABA)A and GABAB receptors, to inhibit GABA reuptake, to evoke GABA release from synaptosomes and to exert an anxiolytic effect that is blocked by the benzodiazepine antagonist flumazenil. Since GABA-ergic mechanisms are known to influence ethanol intake, the present study was aimed at investigating whether they might mediate the effect of a CO2 Hypericum extract (HPCO2) on ethanol intake in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats. Methods: The GABAA receptor antagonist bicuculline and the GABAB receptor antagonists CGP-36742 and phaclofen were tested versus the effect of HPCO2 on ethanol intake. Results: The results of the present study confirm that HPCO2, given by intragastric injection, markedly reduces ethanol intake in msP rats and its effect is behaviourally selective, since the same doses which inhibited ethanol intake did not modify the simultaneous intake of food or water. The GABAA receptor antagonist bicuculline, given by intraperitoneal (i.p.) injection at a dose of 2 mg/kg, which effectively antagonizes the effects of GABAA receptor agonists, did not modify the effect of HPCO2, 15 or 125 mg/kg. The GABAB receptor antagonists CGP-36742, given by i.p. injection at a dose of 100 mg/kg, and phaclofen, given by intracerebroventricular injection at a dose of 25 μg/rat, did not modify the inhibitory effect on alcohol intake induced by HPCO2, 15 or 125 mg/kg. The same doses of the two GABAB receptor antagonists induced a pronounced reduction of the effect of the GABAB receptor agonist bacoflen, given by i.p. injection at a dose of 5 mg/kg. Conclusions: These findings suggest that the inhibitory effects of HPE on ethanol intake are not mediated by GABA agonist actions. [ABSTRACT FROM PUBLISHER] |
