Blockade of gamma-aminobutyric acid receptors does not modify the inhibiton of ethanol intake induced by Hypericum perforatum in rats.
OBJECTIVE
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 gamma-aminobutyric acid (GABA)(A) and GABA(B) 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 GABA(A) receptor antagonist bicuculline and the GABA(B) 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 GABA(A) receptor antagonist bicuculline, given by intraperitoneal (i.p.) injection at a dose of 2 mg/kg, which effectively antagonizes the effects of GABA(A) receptor agonists, did not modify the effect of HPCO2, 15 or 125 mg/kg. The GABA(B) 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 micro g/rat, did not modify the inhibitory effect on alcohol intake induced by HPCO2, 15 or 125 mg/kg. The same doses of the two GABA(B) receptor antagonists induced a pronounced reduction of the effect of the GABA(B) 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.
Perfumi
Marina
M
Department of Pharmacological Sciences and Experimental Medicine, University of Camerino, 62032 Camerino (MC), Italy.
Santoni
Manuela
M
Ciccocioppo
Roberto
R
Massi
Maurizio
M
D000427:Alcohol Deterrents / Q000494:pharmacology*; D000428:Alcohol Drinking / Q000188:drug therapy* / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives* / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000008:administration & dosage* / Q000097:blood; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood; D018756:GABA Antagonists / Q000494:pharmacology; D020902:Hypericum; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology; D010946:Plants, Medicinal; D051381:Rats; D011919:Rats, Inbred Strains; D018079:Receptors, GABA / Q000187:drug effects* / Q000378:metabolism
D000427:Alcohol Deterrents; D002492:Central Nervous System Depressants; D018756:GABA Antagonists; D009943:Organophosphorus Compounds; D010936:Plant Extracts; D018079:Receptors, GABA; C052329:phaclofen; C079148:(3-aminopropyl)(n-butyl)phosphinic acid; D000431:Ethanol; D001418:Baclofen