Blockade of pre- and post-synaptic 5-HT1A receptors does not modify the effect of fluoxetine or 5-hydroxytryptophan on ethanol and food intake in rats.
Ciccocioppo R., Panocka I., Polidori C., Dourish CT., Massi M.
Selective serotonin reuptake inhibitors (SSRIs) or serotonin precursors inhibit ethanol and food intake by increasing the synaptic availability of 5-HT in the central nervous system. However, these agents can also increase 5-HT levels at somatodendritic 5-HT1A autoreceptors, with negative effects on serotonergic transmission. (+)WAY100135 [N-ter-butyl 3-4-(2-methoxy-phenyl) piperazin-1-yl-2-phenylpropanamide dihydrochloride] is a selective antagonist both at pre- and post-synaptic 5-HT1A receptors. The present study investigated the effect on ethanol and food intake of (+)WAY100135, given alone or coadministered with the SSRI fluoxetine or the 5-HT precursor 5-hydroxytryptophan (5-HTP) in genetically selected alcohol-preferring rats. Blockade of presynaptic 5-HT1A receptors after injection of (+)WAY100135, 0.1 or 1 microgram/rat, into the dorsal raphe did not significantly modify ethanol, food or total fluid intake. The same doses of (+)WAY100135 did not modify the inhibition of ethanol and food intake induced by intraperitoneal (i.p.) injection of fluoxetine, 5 mg/kg. Subcutaneous (s.c.) administration of (+)WAY100135 (1 or 10 mg/kg) did not affect the 3-h, or the overnight intake of ethanol, food or total fluids. Given together with i.p. fluoxetine (5 mg/kg) or s.c. 5-HTP (100 mg/kg plus carbidopa. 12.5 mg/kg), the same s.c. doses of (+)WAY100135 did not modify their inhibitory effect on ethanol and food consumption. Present findings suggest that blockade either of pre- or of pre- and postsynaptic 5-HT1A receptors does not potentiate the inhibitory effect of fluoxetine or 5-HTP on ethanol and food intake.