M. Nisell et al., CONDITION-INDEPENDENT SENSITIZATION OF LOCOMOTOR STIMULATION AND MESOCORTICAL DOPAMINE RELEASE FOLLOWING CHRONIC NICOTINE TREATMENT IN THE RAT, Synapse, 22(4), 1996, pp. 369-381
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.