The reinforcing properties of nicotine and psyhomotor stimulants are though
t to be mediated through the mesolimbic dopamine (DA) system. This study in
vestigates the role of high affinity nicotinic acetylcholine receptors (nAC
hRs) in cocaine place preference and examines some neurochemical changes in
the mesolimbic DA system that might account for the interaction between ni
cotine and cocaine. 5 mg/kg is the lowest dose of cocaine able to condition
a place preference in C57Bl/6 mice. Co-treatment with the nicotinic antago
nist mecamylamine (1.0 mg/kg) disrupted place preference to 5 mg/kg cocaine
. In addition, mice lacking the high affinity nAChR containing the beta2 su
bunit showed decreased place preference to 5 mg/kg cocaine, although higher
doses of cocaine could condition a place preference in these knock out ani
mals. In contrast, co-administration of a low dose of nicotine (0.2 mg/kg)
potentiated place preference to a subthreshold dose of cocaine (3 mg/kg). D
A turnover was monitored in several brain regions using tissue levels of DA
and ifs primary metabolite DOPAC as an indication of DA release. Wild type
mice showed decreased DA turnover following treatment with 5 mg/kg cocaine
; whereas, this response was not seen in mice lacking the beta2 subunit of
the nAChR. Induction of chronic fos-related antigens by cocaine was also re
duced in mutant mice as compared to their wild type siblings, implying that
downstream actions of cocaine were also affected by inactivation of the hi
gh affinity nAChR. These data indicate that activation of the high affinity
nAChR may contribute to cocaine reinforcement. (C) 2 001 American College
of Neuropsychopharmacology. Published by Elsevier Science Inc.