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Reduction of cocaine place preference in mice lacking the protein phosphatase 1 inhibitors DARPP 32 or Inhibitor 1

Authors :
Zachariou, Venetia
Benoit-Marand, Marianne
Allen, Patrick B.
Ingrassia, Peter
Fienberg, Allen A.
Gonon, Francois
Greengard, Paul
Picciotto, Marina R.
Source :
Biological Psychiatry. Apr2002, Vol. 51 Issue 8, p612. 9p.
Publication Year :
2002

Abstract

Background: Modulation of protein phosphorylation by dopamine is thought to play an important role in drug reward. Protein phosphatase-1 (PP-1) is known to mediate some of the changes in neuronal signaling that occur following activation of the dopaminergic system.Methods: Two endogenous inhibitors of PP-1 are dopamine and cyclic 3′, 5′ adenosine monophosphate-regulated phosphoprotein (DARPP-32) and Inhibitor-1 (I-1). Knockout mice lacking one or both of these PP-1 inhibitors were tested for responses to cocaine using in vivo amperometry and conditioned place preference.Results: Presynaptic dopaminergic function appears to be unaffected by these mutations because stimulation-evoked changes in extracellular dopamine levels were unchanged between wild type mice and mice lacking one or both of these PP-1 inhibitors. In contrast, conditioned place preference to cocaine is reduced in mice lacking DARPP-32, I-1, or both phosphoproteins. This does not appear to be due to a learning deficit because mice lacking both DARPP-32 and I-1 show normal passive avoidance learning.Conclusions: These data imply that increased PP-1 function as a result of deficits in DARPP-32 or I-1 is sufficient to decrease the rewarding properties of cocaine. Furthermore, the mechanism for this altered cocaine place preference does not involve alteration of dopamine release or reuptake. [Copyright &y& Elsevier]

Details

Language :
English
ISSN :
00063223
Volume :
51
Issue :
8
Database :
Academic Search Index
Journal :
Biological Psychiatry
Publication Type :
Academic Journal
Accession number :
8784757
Full Text :
https://doi.org/10.1016/S0006-3223(01)01318-X