Effects of 5-HT1A and 5-HT2 Receptor Agonists on the Behavioral and Neurochemical Consequences of Repeated Nicotine Treatment

This study investigated the effects of repeated daily (15 days) treatment with nicotine, alone or in combination with the 5-HT1A/7 receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) or the 5-HT2 receptor agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine (DOI) on locomotor sensitization, mesolimbic dopamine neurochemistry and on behavioral inhibition in the rat. Acute nicotine elevated the extracellular dopamine levels in the nucleus accumbens and stimulated locomotor activity, effects that were sensitized after repeated nicotine treatment. Repeated nicotine administration also produced nicotine-induced behavioral disinhibition in the elevated plus-maze. Treatment with DOI counteracted the expression of the nicotine-induced locomotor and neurochemical sensitization, but had no effect on nicotine-induced behavioral disinhibition. Treatment with 8-OH-DPAT decreased the expression of nicotine-induced behavioral disinhibition, but had no effect on locomotor or neurochemical sensitization. Taken together, these findings suggest that the 5-HT1A and the 5-HT2 receptor subtypes are differentially involved in the effects of repeated nicotine on locomotor sensitization, behavioral inhibition and mesolimbic dopamine neurochemistry.