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Br J Pharmacol. 2011 Apr;162(8):1770-80. doi: 10.1111/j.1476-5381.2010.01193.x.

Dopaminergic mechanisms of reinstatement of MDMA-seeking behaviour in rats.

Author information

1
Victoria University of Wellington, School of Psychology, Wellington, New Zealand. susan.schenk@vuw.ac.nz

Abstract

BACKGROUND AND PURPOSE:

Animal models of drug-seeking suggest that exposure to cues associated with self-administered drugs and drug primes might precipitate relapse via activation of central dopaminergic substrates.

EXPERIMENTAL APPROACH:

The effects of priming injections of dopamine and 5-HT agonists on drug-seeking and effects of dopamine antagonists on methylenedioxymethamphetamine (MDMA)-produced potentiation of drug-seeking following extinguished MDMA self-administration were examined.

KEY RESULTS:

Drug-seeking was produced by exposure to a light stimulus that had been paired with self-administered MDMA infusions and this effect was potentiated by experimenter-administered injections of the dopamine D(2) -like receptor agonist, quinpirole, the indirect agonist, amphetamine and the uptake inhibitor, GBR 12909. Drug-seeking was not elicited by the dopamine D(1) -like receptor agonist, SKF 81297 or the non-selective agonist, apomorphine. The 5-HT receptor agonists DOI or mCPP also failed to elicit drug-seeking. The 5-HT uptake inhibitor, clomipramine, attenuated drug-seeking produced by the MDMA-associated stimulus but failed to alter the potentiated response produced by GBR 12909. The D(1) receptor antagonist, SCH 23390 or the D(2) receptor antagonist, eticlopride attenuated the potentiation of drug-seeking produced by MDMA.

CONCLUSIONS AND IMPLICATIONS:

These data provide evidence of dopaminergic mechanisms in drug-seeking following extinction of MDMA self-administration. Because tissue levels of 5-HT were significantly decreased following MDMA self-administration, we suggest that MDMA begins to preferentially activate dopaminergic substrates to potentiate the drug-seeking response.

PMID:
21198550
PMCID:
PMC3081120
DOI:
10.1111/j.1476-5381.2010.01193.x
[Indexed for MEDLINE]
Free PMC Article
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