Effects of serotonin (5-HT)6 receptor ligands on responding for cocaine reward and seeking in rats

The endogenous brain serotonin (5-ht) system is believed to have an important modulatory influence in mediating drug reward and seeking mechanisms. data from preclinical behavioral studies have provided emerging evidence that 5-ht6 receptors,among other 5-ht receptors,may play a significant role in the mechanisms of action of psychostimulant addicted drugs. the aim of the present study was to investigate whether the selective pharmacological blockade or activation of 5-ht6 receptors altered the maintenance of cocaine self-administration,reinstatement of cocaine-seeking behavior following an extinction of cocaine self-administration or cocaine-evoked conditioned place preference in rats. we also evaluated the effects of 5-chloro-n-(4- methoxy-3-piperazin-1-ylphenyl)-3-methyl)-2-benzothiophene-sulfonamide (sb 271046,a 5-ht6 receptor antagonist) or n-1-(6-chloroimidazo-[2,1-b]- [1,3]thiazole-5-sulfonyl)tryptamine (way 181187,a potent 5-ht6 receptor agonist) on locomotor activity in rats. our results indicate that sb 271046 (1-10 mg/kg) altered cocaine-maintained self-administration as well as cocaine-evoked reinstatement of cocaine seeking and expression of cocaine place preference in rats.we also demonstrate that pharmacological stimulation of 5-ht6 receptors by way 181187 (3-30 mg/kg) attenuated the expression of cocaine conditioned place preference but not cocaine selfadministration and reinstatement of cocaine seeking. way 181187 at the highest dose used (30 mg/kg) reduced basal locomotor activity. despite current results,the precise function and therapeutic relevance of 5-ht6 receptors need further clarification. copyright © 2010 by institute of pharmacology polish academy of sciences.