The influence of lobeline on nucleus accumbens dopamine and locomotor responses to nicotine in nicotine-pretreated rats

Abstract

1 In vivo brain microdialysis was used to investigate the influence of lobeline on dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) overflow in the core of the nucleus accumbens of freely-moving rats pretreated with nicotine (0.4 mg kg-1 s.c., once per day for 5 days). Locomotion was also recorded. 2 Lobeline, at doses of 0.7, 4.0 and 10.0 mg kg-1, i.p., failed to elicit any significant changes in extracellular dopamine or dihydroxyphenylacetic acid levels during the 60 min following its administration and did not stimulate locomotor. 3 The dopamine 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 unaffected 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 injected 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 the nicotinic AChRs which mediate the effects of nicotine on mesolimbic dopamine activity and locomotor stimulation.