BRAIN SITES MEDIATING THE DISCRIMINATIVE STIMULUS EFFECTS OF NICOTINEIN RATS

Pharmacological studies suggest that the discriminative stimulus (DS) produced by nicotine is mediated centrally. The aim of the present stu dy was to identify neuroanatomical substrates that mediate the DS prop erties of nicotine. Specifically, the nucleus accumbens, a brain regio n known to mediate the DS effects of amphetamine and cocaine, was inve stigated using a two-lever operant drug discrimination paradigm. Male hooded rats were trained to discriminate nicotine (0.2 mg/kg s.c.) fro m saline with a tandem schedule of food reinforcement. Once stimulus c ontrol was attained, a randomised sequence of nicotine microinjections (2-8 mu g) was tested for generalisation during brief extinction test s. It was confirmed that the stimulus produced by the systemic adminis tration of nicotine generalized to nicotine administered bilaterally i nto the dorsal hippocampus, with significant decreases in overall resp onse rates. Microinjections of nicotine (1-8 mu g) into the nucleus ac cumbens failed to produce any dose-related increases in responding on the nicotine-appropriate lever although these microinjections also pro duced significant decreases in response rates. Smaller doses (1-4 mu g ) of nicotine administered into the fourth ventricle produced characte ristic prostration responses but these microinjections failed to produ ce generalization in tests carried out 20 min later, when the disablin g effects of prostration had dissipated. These results suggest that th e DS effects of nicotine may be mediated, at least in part, through th e dorsal hippocampus. Results from intra-accumbens and intraventricula r injections suggest that these regions may not be important in mediat ing the DS effects of nicotine.