THE IMPACT OF 3,4-METHYLENDIOXYMETHAMPHETAMINE (MDMA) ABSTINENCE ON SEEKING BEHAVIOR AND THE EXPRESSION OF THE D2-LIKE AND MGLU5 RECEPTORS IN THE RAT BRAIN USING SATURATION BINDING ANALYSES

The abundance of research indicates that enriched environment acts as a beneficial factor reducing the risks of relapse in substance use disorder. There is also strong evidence showing the engagement of brain dopaminergic and glutamatergic signaling through the dopamine D-2-like and metabotropic glutamate type 5 (mGlu(5)) receptors, respectively, that has a direct impact on drug reward and drug abstinence. The present study involved 3,4-methylendioxymethamphetamine (MDMA) self-administration with the yoked-triad procedure in rats kept under different housing conditions during abstinence - enriched environment (EE) or isolation cage (IC) conditions - aimed at evaluating changes in brain receptors affecting drug-seeking behavior as well as density and affinity of the D-2-like and mGlu(5) receptors in several regions of the animal brain. Our results show that exposure to EE conditions strongly reduced active lever presses during cue-induced drug-seeking. At the neurochemical level, we demonstrated marked decreases of D-2-like receptor affinity in the dorsal striatum in rats previously self-administering MDMA under EE and increases in density under IC conditions. Moreover, we found the increases in the density and decreases in the affinity of the D-2-like receptor in the prefrontal cortex and nucleus accumbens provoked by IC conditions. The mGlu(5) receptor density decreased only in the prefrontal cortex after IC and EE abstinence. Moreover, our study has revealed a clear decrease in mGlu(5) receptor density in the nucleus accumbens in the group actively administering MDMA only under EE conditions. This study demonstrates that housing conditions have impact on drug-seeking behavior in rats during abstinence from MDMA self-administration. The observed changes in the dopamine D-2-like and mGlu(5) receptor B-max and/or K-d values were brain-region specific and related to either pharmacological and/or motivational features of MDMA.