BLOCKADE OF PRE-SYNAPTIC AND POSTSYNAPTIC 5-HT1A RECEPTORS DOES NOT MODIFY THE EFFECT OF FLUOXETINE OR 5-HYDROXYTRYPTOPHAN ON ETHANOL AND FOOD-INTAKE IN RATS

Selective serotonin reuptake inhibitors (SSRIs) or serotonin precursor s inhibit ethanol and food intake by increasing the synaptic availabil ity of 5-HT in the central nervous system. However, these agents can a lso increase 5-HT levels at somatodendritic 5-HT1A autoreceptors, with negative effects on serotonergic transmission. (+)WAY100135 [N-ter-bu tyl 3-4-(2-methoxy-phenyl) piperazin-1-yl-2-phenylpropanamide dihydroc hloride] is a selective antagonist both at pre- and post-synaptic 5-HT 1A receptors. The present study investigated the effect on ethanol and food intake of (+)WAY100135, given alone or coadministered with the S SRI fluoxetine or the 5-HT precursor 5-hydroxytryptophan (5-HTP) in ge netically selected alcohol-preferring rats. Blockade of presynaptic 5- HT1A receptors after injection of (+)WAY100135, 0.1 or 1 mu g/rat, int o the dorsal raphe did not significantly modify ethanol, food or total fluid intake. The same doses of (+)WAY100135 did not modify the inhib ition of ethanol and food intake induced by intraperitoneal (IP) injec tion of fluoxetine, 5 mg/kg. Subcutaneous (SC) administration of (+)WA Y100135 (1 or 10 mg/kg) did not affect the 3-h, or the overnight intak e of ethanol, food or total fluids. Given together with IP fluoxetine (5 mg/kg) or SC 5-HTP (100 mg/kg plus carbidopa, 12.5 mg/kg), the same SC doses of (+)WAY100135 did not modify their inhibitory effect on et hanol and food consumption. Present findings suggest that blockade eit her of pre-or of pre- and postsynaptic 5-HT1A receptors does not poten tiate the inhibitory effect of fluoxetine or 5-HTP on ethanol and food intake.