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Psychopharmacology (Berl). 2004 Sep;175(2):154-62. Epub 2004 Feb 25.

The sigma1 (sigma1) receptor activation is a key step for the reactivation of cocaine conditioned place preference by drug priming.

Author information

1
CNRS FRE 2693, University of Montpellier II, place Eugène Bataillon, 34095, Montpellier 5, France.

Abstract

RATIONALE:

Cocaine-seeking behavior can be investigated in rodents using the conditioned place preference (CPP) paradigm, in which the drug-paired environment serves as a conditioned stimulus. Such approach allowed to previously demonstrate the importance of the neuromodulatory sigma1 (sigma1) receptor in acquisition of cocaine-induced CPP. CPP can be extinguished and then reactivated, notably using a cocaine challenge (i.e., priming).

OBJECTIVES AND METHODS:

In order to examine the role of the sigma1 receptor in reinstatement of Cocaine-seeking, Swiss mice acquired CPP with cocaine (30 mg/kg, i.p.) and then CPP was extinguished.

RESULTS:

A challenge cocaine priming (15 mg/kg) reactivated CPP up to 140% of the post-conditioning response. Pre-administration of the sigma1 receptor antagonist BD1047 (330 mg/kg, i.p.) or repeated treatment with an antisense probe targeting the sigma1 receptor prevented CPP reactivation. The sigma1 agonist igmesine (1-10 mg/kg, i.p.) or the steroid dehydroepiandrosterone (DHEA, 10-40 mg/kg, s.c.) reactivated CPP, in a BD1047-sensitive manner. Moreover, the in vivo [3H](+)-SKF-10,047 binding levels to the sigma1 receptor were increased after cocaine conditioning in numerous brain structures and these increases subsisted after extinction. Finally, cross-reactivation of cocaine-induced CPP was observed after phencyclidine (PCP), morphine, nicotine and ethanol administration. However, BD1047 blocked reactivation of CPP induced by PCP, morphine and nicotine but not ethanol.

CONCLUSIONS:

Since activation of the sigma1 receptor is not sufficient to sustain CPP in naive animals [Neuropsychopharmacology 26 (2002) 444], it is concluded that sigma1 receptor activation is a key event for relapse to drug seeking. Activation may occur via sensitization due to enhanced in vivo available of receptors.

PMID:
14985920
DOI:
10.1007/s00213-004-1814-x
[Indexed for MEDLINE]

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