Dopamine, norepinephrine and serotonin transporter gene deletions differentially alter cocaine-induced taste aversion

Jermaine D. Jones, F. Scott Hall, George R. Uhl, Anthony L. Riley

Research output: Contribution to journalArticle

Abstract

Although cocaine is primarily known for its powerful hedonic effects, there is evidence that its affective experience has a notable aversive component that is less well understood. A variety of pharmacological and molecular approaches have implicated enhanced monoamine (MA) neurotransmission in the aversive effects of cocaine. Although numerous studies have yielded data supportive of the role of the monoamines (indirectly and directly), the specific system suggested to be involved differs across studies and paradigms (Freeman et al., 2005b; Grupp, 1997; Roberts and Fibiger, 1997). Monoamine transporter knockout mice have been useful in the study of many different aspects of cocaine effects relevant to human drug use and addiction, yet an assessment of the effects of deletion of the genes for the dopamine, norepinephrine and serotonin transporters (DAT, NET, and SERT, respectively) on cocaine's aversive properties has yet to be performed (Uhl et al., 2002). In the current investigation, the strength of cocaine-induced aversions was compared among three groups of transgenic mice with deletions of the genes responsible for the production of one of the monoamine transporters. When compared to their respective WT controls, dopamine transporter deletion slightly attenuated cocaine-induced aversion while deletion of SERT or NET resulted in a more significant delay in the onset and strength of cocaine-induced taste aversions. The data lead us to conclude that the action of cocaine to inhibit NET contributes most substantially to its aversive effects, with some involvement of SERT and minimal contribution of DAT.

Original languageEnglish (US)
Pages (from-to)580-587
Number of pages8
JournalPharmacology Biochemistry and Behavior
Volume94
Issue number4
DOIs
StatePublished - Feb 2010
Externally publishedYes

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Keywords

  • Cocaine
  • DAT
  • Knockout
  • Monoamine
  • NET
  • SERT
  • Taste aversion

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Pharmacology
  • Toxicology
  • Behavioral Neuroscience
  • Biological Psychiatry

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