THE INFLUENCE OF LOBELINE ON NUCLEUS-ACCUMBENS DOPAMINE AND LOCOMOTORRESPONSES TO NICOTINE IN NICOTINE-PRETREATED RATS

1 In vivo brain microdialysis was used to investigate the influence of lobeline on dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) over flow in the core of the nucleus accumbens of freely-moving rats pretre ated with nicotine (0.4 mg kg(-1), s.c., once per day for 5 days). Loc omotion was also recorded. 2 Lobeline, at doses of 0.7, 4.0 and 10.0 m g kg(-1), i.p., failed to elicit any significant changes in extracellu lar dopamine or dihydroxyphenylacetic acid levels during the 60 min fo llowing its administration and did not stimulate locomotor. 3 The dopa mine responses to nicotine (0.4 mg kg(-1), s.c.), were abolished (P<0. 01) if the nicotine challenge was administered 10 min but not 60 min, after lobeline doses of 4.0 and 10.0 mg kg(-1), i.p., but were unaffec ted following lobeline at the lowest dose tested (0.7 mg kg(-1), i.p.) at either time. The increase in locomotor activity was significantly attenuated (P<0.01), to a similar extent, when the nicotine was inject ed 10 min, but not 60 min, after all three doses of lobeline (0.7, 4.0 and 10.0 mg kg(-1) i.p.) when compared with the saline-treated rats. 4 The results suggest that lobeline is a short-acting antagonist of th e nicotinic AChRs which mediate the effects of nicotine on mesolimbic dopamine activity and locomotor stimulation.