CONDITION-INDEPENDENT SENSITIZATION OF LOCOMOTOR STIMULATION AND MESOCORTICAL DOPAMINE RELEASE FOLLOWING CHRONIC NICOTINE TREATMENT IN THE RAT

Chronic nicotine (NIC) pretreatment has been shown to enhance NIC-indu ced locomotor stimulation, an effect that seems critically dependent o n activation of brain dopamine (DA) systems. In the present study the effects of chronic, intermittent NIC treatment were examined in the ra t to establish whether such behavioral sensitization is associated wit h specific, regional changes in brain dopaminergic activity. Male rats received daily injections in their home cage with either saline (SAL) or NIC (0.5 mg/kg, s.c.) for 12 days. Twenty-four hours later, the lo comotor activity of the animals subjected to NIC challenge as well as the functional responsiveness of the mesolimbocortical dopaminergic sy stem were assessed. To this end, microdialysis experiments were perfor med in awake animals, measuring extracellular concentrations of DA and its metabolites in the prefrontal cortex (PFC) and the nucleus accumb ens (NAG). Extracellular single cell recordings from DA neurons in the ventral tegmental area (VTA) were also performed in anesthetized anim als. NIC (0.5 mg/kg, s.c.) increased all measured parameters of locomo tor activity, with the exception of rearing, in SAL-pretreated animals ; these effects were substantially enhanced after pretreatment with NI C. Nicotine (0.5 mg/kg, s.c.) increased DA release in both the PFC and the NAC in SAL-treated animals. Nicotine pretreatment significantly e nhanced this effect in the PFC, whereas it did not affect the response in the NAC. Low doses of intravenously administered NIC dose-dependen tly increased burst activity, starting at 12 mu g/kg in the SAL pretre ated animals and at 6 mu g/kg in the NIC-pretreated animals, and also dose-dependently increased firing rate in SAL as well as NIC-pretreate d animals, although starting at a higher dose level, i.e., 25 mu g/kg. These results demonstrate that behavioral sensitization after chronic NIC treatment is accompanied by an enhanced dopamine release specific ally within the PFC. This phenomenon may be highly significant for the dependence-producing effects of NIC, particularly in association with major psychiatric disorder, such as schizophrenia. (C) 1996 Wiley-Lis s, Inc.