Reducing effect of the positive allosteric modulator of the GABA(B) receptor, GS39,783, on alcohol self-administration in alcohol-preferring rats.
OBJECTIVE
The positive allosteric modulator of the GABA(B) receptor, GS39,783, has recently been found to suppress acquisition and maintenance of alcohol drinking behavior in selectively bred Sardinian alcohol-preferring (sP) rats exposed to the standard, homecage two-bottle "alcohol vs water" choice regimen. The present study was designed to extend the characterization of the "anti-alcohol" effects of GS39,783 to oral self-administration of alcohol under an operant procedure.


METHODS
Two separate groups of male sP rats were trained to lever-press (on an FR4 schedule) to orally self-administer alcohol (15%, v/v) or sucrose (0.3%, w/v) in daily 30-min sessions. Once lever-pressing behavior reached stable levels, the effect of GS39,783 (0, 25, 50, and 100 mg/kg, i.g.) on responding for alcohol and sucrose was determined.


RESULTS
Pretreatment with GS39,783 resulted in a significant, dose-dependent reduction in responding for alcohol; at the dose of 100 mg/kg GS39,783, the number of lever responses for alcohol was reduced by approximately 50% in comparison to vehicle-treated rats. The effect of GS39,783 on alcohol self-administration was specific, as responding for sucrose was completely unaffected by pretreatment with GS39,783.


CONCLUSIONS
These data demonstrate the capability of GS39,783 to attenuate the reinforcing properties of alcohol in alcohol-preferring rats. These data constitute a further piece of experimental evidence in support of the hypothesized role for the GABA(B) receptor in the control of alcohol drinking and reinforcement.
Maccioni
Paola
P
"Bernard B. Brodie" Department of Neuroscience, University of Cagliari, Viale Diaz 182, 09126, Cagliari, Italy.
Pes
Daniela
D
Orrù
Alessandro
A
Froestl
Wolfgang
W
Gessa
Gian Luigi
GL
Carai
Mauro A M
MA
Colombo
Giancarlo
G
D000428:Alcohol Drinking / Q000517:prevention & control* / Q000523:psychology; D000494:Allosteric Regulation; D000818:Animals; D003216:Conditioning, Operant; D003517:Cyclopentanes / Q000494:pharmacology*; D000431:Ethanol / Q000008:administration & dosage; D018757:GABA Modulators / Q000494:pharmacology*; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D018080:Receptors, GABA-B / Q000187:drug effects*; D012054:Reinforcement, Psychology; D012646:Self Administration
D003517:Cyclopentanes; D018757:GABA Modulators; C478058:N,N'-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine; D011743:Pyrimidines; D018080:Receptors, GABA-B; D000431:Ethanol