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Involvement of the sigma(1) receptor in cocaine-induced conditioned place preference: Possible dependence on dopamine uptake blockade

Academic Article
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Overview

authors

  • Romieu, P.
  • Phan, V. L.
  • Martin-Fardon, Remi
  • Maurice, T.

publication date

  • April 2002

journal

  • Neuropsychopharmacology  Journal

abstract

  • The involvement of the sigma(1) receptor on the rewarding effects of cocaine was examined using the conditioned place preference (CPP) procedure in C57BL/6 mice. Acquisition or expression of cocaine (20 mg/kg i.p.)-induced CPP was significantly decreased by pre-treatment with the selective sigma(1) receptor antagonists N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine (NE-100) or N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine (BD1047), 1-10 mg/kg, i.p. The sigma(1) receptor agonists igmesine or 2-(4-morpholinoethyl-1-phenylcyclohexane-1-carboxylate hydrochloride (PRE-084) failed to induce CPP when injected alone. Moreover, the CPP induced by N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine (BTCP), a selective dopamine reuptake inhibitor, was blocked by treatments with the sigma(1) receptor antagonists as was similarly observed with cocaine. In addition, the repetitive treatment with cocaine during conditioning increased sigma(1) receptor mRNA expression in the nucleus accumbens, but not in the caudate putamen, prefrontal cortex or cerebellum. These data show that the sigma(1) receptor is not only necessary for acquisition of the cocaine-induced CPP, but that it is also implicated in its expression, confirming that activation of the sigma(1) receptor is induced during cocaine's early effects. The sigma(1) receptor is activated consequently to dopamine reuptake blockade and is not sufficient to induce CPP by itself. The mechanism of the sigma(1) receptor involvement in CPP and the selectivity toward the CPP-inducing drug remains however to be determined. These results show that strategies targeting the sigma(1) receptor with selective antagonists may allow effective attenuation of cocaine's rewarding properties and, in turn, offer new treatment strategies against drug addiction.

subject areas

  • Animals
  • Anxiety
  • Brain Chemistry
  • Cocaine
  • Conditioning, Operant
  • Dopamine Uptake Inhibitors
  • Dose-Response Relationship, Drug
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity
  • RNA, Messenger
  • Receptors, sigma
  • Reverse Transcriptase Polymerase Chain Reaction
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Research

keywords

  • C57B1/6 mouse
  • cocaine
  • conditioned place preference
  • dopamine reuptake
  • reward
  • sigma(1) receptor
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Identity

International Standard Serial Number (ISSN)

  • 0893-133X

Digital Object Identifier (DOI)

  • 10.1016/s0893-133x(01)00391-8

PubMed ID

  • 11927169
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Additional Document Info

start page

  • 444

end page

  • 455

volume

  • 26

issue

  • 4

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