Restraint stress prevents nicotine-induced dopamine release in nucleus accumbens shell. A microdialysis study in the rat

Nicotine (NIC) is the major psychoactive agent in tobacco smoke, and one of the most heavily used addictive drug in the world. NIC shares with many other drugs abused by humans the ability to stimulate the activity of the dopamine (DA) mesolimbic system (1). In particular, the release of DA in the nucleus accumbens shell (NAcbs) has been consistently related to the motivation properties of several abused drugs including NIC (2). It is well known that exposure to stress exerts a large influence on the behaviour of tobacco addicted, increasing drug intake and the urge to smoke, as well as being the most common cause of relapse. Interestingly a substantial amount of data indicate the mesolimbic DA system as a common neural substrate of both abused drugs and stress activities on the central nervous system. On these basis, we decided to investigate the in vivo effect of exposure to acute restraint stress on nicotine-induced dopamine release in the NAcbs. Experiments were performed in adult male Wistar rats. Dialysis probes were implanted in the NAcbs and dialysates analysed by HPLC with coulometric detection. NIC was administered intravenously at a dose of 16, 32, 65 and 130 μg/kg (free base). In the stressed group, rats were exposed to a one-hour of restraint stress before NIC administration. It has been reported that acute exposure to restraint stress increases DA outflow in the NAcbs in a distinct biphasic way, with a first increase during the stress procedure followed by a second increase as soon as restraint ceases (3). Therefore, in order to avoid interferences, NIC was administered only after the return of DA levels to its basal values (one hour after exposure to stress). NIC administration dose-dependently significantly increases (up to 50% from baseline) DA extracellular levels in the NAcbs in control rats, but not in subjects acutely exposed to one hour of restraint stress. Our data indicate that the neural correlated of restraint stress are able to profoundly influence the response to NIC of the mesolimbic DA system, suggesting the possibility of a reduced effects of NIC in stressed individuals thus encouraging an enhanced drug-taking behaviour. Nisell M., Pharmacol Toxicol, 1994 Piazza P.V., TIPS, 1998 Imperato A., Brain Res.1992