Studio dell'effetto dell'attivazione del recettore GABAB sul consumo di alcol e sulle proprietà motivazionali dell'alcol nel ratto

GABA is a major inhibitory neurotransmitter in the brain. Recent preclinical evidence suggests that pharmacological activation of the GABAB receptor (one of the two receptorstypes to which GABA may bind) reduced alcohol intake and ameliorated alcohol in take and ameliorated alcohol withdrawal syndrome. The recent discovery of a modulatory binding site within the GABAB receptor, together with the synthesis of in vivo effective drugs with positive allosteric modulatory activity, provide novel tools for investigations on the role of the GABAB receptor in the mediation of alcohol-related behaviors. The aim of the present study was twofold: (a) investigating the effect of GABAB receptor direct agonists on alcohol�?s reinforcing and motivational properties, and (b) extending the investigation to some GABAB receptor positive allosteric modulators (PAMs). Selectively bred, Sardinian alcohol preferring (sP) rats (an animal model of alcoholism) were initially trained to press a lever to gain access to alcohol (index of the reinforcing and motivational properties of alcohol) under standard procedure of oral alcohol self-administration. Injection of non-sedative doses of both baclofen (direct agonist) and GS39383 (PAM) resulted in statistically, dose-dependent reduction of the rats' responding on the, alcohol-associated lever. These data suggest that activation of the GABAB receptor-either by mean of direct agonists or PAMs - may suppress alcohol reinforcement and motivation to consume alcohol.