STUDIES ON THE INFLUENCE OF NICOTINE INFUSIONS ON MESOLIMBIC DOPAMINEAND LOCOMOTOR RESPONSES TO NICOTINE

The present study examined the effects of constant nicotine infusions on dopamine overflow in the nucleus accumbens and on locomotor activit y and compared them with the changes evoked by repeated daily injectio ns (one injection per day for 5 days) of the drug. The putative anxiol ytic properties of nicotine have also been examined using the elevated plus-maze test of anxiety. Repetitive daily subcutaneous injections o f nicotine (0.4 mg/kg) enhanced (P < 0.01) the overflow of dopamine ev oked by a challenge dose of the drug (0.4 mg/kg) and increased (P < 0. 01) its stimulatory effects on locomotor activity. The constant infusi on of nicotine, at doses of 1 and 4 mg/kg per day, abolished (P < 0.05 ) the effects of a bolus injection of nicotine on extracellular dopami ne and attenuated (Pi < 0.01) the enhanced locomotor response evoked b y daily pretreatment with nicotine boli. The mesolimbic dopamine respo nse to a bolus injection of nicotine was not significantly attenuated by nicotine infusions when the dose was reduced to 0.25 mg/kg per day. The locomotor responses in these rats were significantly (P < 0.05) l ess than those seen in the animals pretreated with nicotine injections alone but were also higher (P < 0.05) than those seen in saline-treat ed control rats given a bolus injection of nicotine. Neither the const ant infusion (4 mg/kg per day) nor the injection of nicotine (0.4 mg/k g) evoked an anxiolytic or anxiogenic effect in the elevated plus-maze test. However, the nicotine infusions did abolish the locomotor stimu lant effects of the drug in this apparatus. They also abolished the pl asma corticosterone response to nicotine and attenuated the plasma cor ticosterone response to the maze. The data suggest that constant infus ions of nicotine, at doses of 1 mg/kg per day or more, may cause desen sitisation of the nicotinic receptors which mediate the stimulatory ef fects of the drug on mesolimbic dopamine release and locomotor activit y. The data also suggest that the receptors which mediate the increase in plasma corticosterone, seen in animals given nicotine boli, may al so be desensitised by nicotine infusions, and that these receptors may be implicated in the adrenocortical response to anxiogenic stimuli.