Extinction training following cocaine or MDMA self-administration produces discrete changes in D₂-like and mGlu₅ receptor density in the rat brain

Background: Several studies strongly support the role of the dopamine D₂-like and glutamate mGlu₅ receptors in psychostimulant reward and relapse.

Methods: The present study employed cocaine or MDMA self-administration with yoked-triad procedure in rats to explore whether extinction training affects the drug-seeking behavior and the D₂-like and mGlu₅ receptor B_max and K_d values in several regions of the animal brain.

Results: Both cocaine and MDMA rats developed maintenance of self-administration, but MDMA evoked lower response rates and speed of self-administration acquisition. During reinstatement tests, cocaine or MDMA seeking behavior was produced by either exposure to the drug-associated cues or drug-priming injections. The extinction training after cocaine self-administration did not alter significantly D₂-like receptor expression the in the limbic and subcortical brain areas, while MDMA yoked rats showed a decrease of the D_2-like binding density in the nucleus accumbens and increase in the hippocampus and a rise of affinity in the striatum and hippocampus. Interestingly, in the prefrontal cortex a reduction in the mGlu₅ receptor density in cocaine- or MDMA-abstinent rats was demonstrated, with significant effects being observed after previous MDMA exposure. Moreover, rats self-administered cocaine showed a rise in the density of mGlu₅ receptor for the nucleus accumbens.

Conclusion: This study first time shows that abstinence followed extinction training after cocaine or MDMA self- or passive-injections changes the D₂-like and mGlu₅ density and affinity. The observed changes in the expression of both receptors are brain-region specific and related to either pharmacological and/or motivational features of cocaine or MDMA.