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Stop Animal
Exploitation NOW!
S. A. E. N.
"Exposing the truth to wipe
out animal experimentation"
 Articles and
Reports
Journal Article of Cocaine Effects on Animals by M. Caroll, A. Morgan, A. Loth, M. Stoffel, and K. Wickman
Neuropsychopharmacology (2003) 28, 932–938, advance online
publication, 5 March 2003; doi:10.1038/sj.npp.1300100
Decreased Cocaine Self-Administration in Kir Potassium Channel
Subunit Knockout Mice
Andrew D Morgan1, Marilyn E Carroll, Annemarie K Loth, Markus Stoffel
and Kevin Wickman
1. Department of Psychiatry, University of Minnesota, Minneapolis,
MN, USA
2. Laboratory of Metabolic Diseases, The Rockefeller University, New
York, NY, USA
3. Department of Pharmacology, University of Minnesota, Minneapolis, MN,
USA
Correspondence: Dr K Wickman, Department of Pharmacology, University
of Minnesota, 6-120 Jackson Hall, 321 Church Street SE, Minneapolis, MN
55455, USA. Tel: +1 612 624 5966; Fax: +1 612 625 8408; E-mail:
wickm002@tc.umn.edu
Received 4 June 2002; Revised 16 October 2002; Accepted 18 October 2002;
Published online 5 March 2003.
Abstract
Multiple G protein-linked neurotransmitter systems have been implicated
in the behavioral effects of cocaine. While actions of certain
neurotransmitter receptor subtypes and transporters have been
identified, the role of individual G protein-regulated enzymes and ion
channels in the effects of cocaine remains unclear. Here, we assessed
the contribution of G protein-gated, inwardly rectifying potassium
(Kir3/GIRK) channels to the locomotor-stimulatory and reinforcing
effects of cocaine using knockout mice lacking one or both of the key
neuronal channel subunits, Kir3.2 and Kir3.3. Cocaine-stimulated
increases in horizontal locomotor activity in wild-type, Kir3.2
knockout, Kir3.3 knockout, and Kir3.2/3.3 double knockout mice, with
only minor differences observed between the mouse lines. In contrast,
Kir3.2 and Kir3.3 knockout mice exhibited dramatically reduced
intravenous self-administration of cocaine relative to wild-type mice
over a range of cocaine doses. Paradoxically, Kir3.2/3.3 double knockout
mice self-administered cocaine at levels significantly higher than
either single knockout alone. These findings suggest that Kir3 channels
play significant and complex roles in the reinforcing effect of cocaine.
Keywords:
cocaine, locomotor activity, mouse, self-administration, potassium
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See
University of Minnesota for additional
information.
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