Extinction training following cocaine or MDMA self-administration produces discrete changes in D2-like and mGlu5 receptor density in the rat brain.
Małgorzata Frankowska, Joanna Miszkiel, Lucyna Pomierny-Chamioło, Bartosz Pomierny, Andrea Celeste Borelli, Agata Suder, Malgorzata Filip
Pharmacological reports : PR October 2019 DOI: 10.1016/j.pharep.2019.05.001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Rats self-administering cocaine or MDMA, with yoked passive-injection controls |
| Interventions | Cocaine MDMA |
| Topics | MDMA |
| Keywords | Cocaine self-administration Dopamine d2-like receptor Extinction training Glutamate mglu5 receptor MDMA Self-Administration Reinstatement of seeking-behavior |
| Key findings | Extinction training after cocaine or MDMA self- or passive-injections altered D2-like and mGlu5 receptor density and affinity in a brain-region-specific manner. Cocaine did not significantly change D2-like receptor expression in limbic and subcortical areas, but increased mGlu5 density in the nucleus accumbens. MDMA decreased D2-like binding density in the nucleus accumbens, increased it in the hippocampus, raised affinity in the striatum and hippocampus, and was associated with the most pronounced reduction in prefrontal cortex mGlu5 density. |
Abstract
Several studies strongly support the role of the dopamine D2-like and glutamate mGlu5 receptors in psychostimulant reward and relapse. 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 Bmax and Kd values in several regions of the animal brain. 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 D2-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. 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.