Dopaminergic mechanisms of reinstatement of MDMA‐seeking behaviour in rats
British Journal of Pharmacology – December 30, 2010
Source: OpenAlex
Summary
Exposure to cues linked to self-administered MDMA significantly triggered drug-seeking behavior, with a notable 70% increase when paired with the dopamine D2-like receptor agonist quinpirole. In contrast, other dopamine and serotonin receptor agonists did not elicit similar responses. The study involved animal models and highlighted that dopamine antagonists effectively reduced the heightened drug-seeking induced by MDMA. These findings underscore the critical role of dopaminergic pathways in reinforcing drug-seeking behaviors after the cessation of MDMA use, emphasizing implications for addiction treatment strategies.
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.