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Pharmacol Rep. 2019 May 7;71(5):870-878. doi: 10.1016/j.pharep.2019.05.001. [Epub ahead of print]

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

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Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Drug Addiction Pharmacology, Kraków, Poland. Electronic address:
Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Drug Addiction Pharmacology, Kraków, Poland.
Department of Toxicology, Faculty of Pharmacy, Jagiellonian University Collegium Medicum, Medyczna 9, 30-688, Kraków, Poland.
Department of of Medical Sciences, University of Ferrara, Ferrara, Italy.



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.


Cocaine self-administration; Dopamine D(2)-like receptor; Extinction training; Glutamate mGlu(5) receptor; MDMA self-administration; Reinstatement of seeking-behavior

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