PMID- 33316768 OWN - NLM STAT- MEDLINE DCOM- 20210824 LR - 20210824 IS - 1899-1505 (Electronic) IS - 0867-5910 (Linking) VI - 71 IP - 4 DP - 2020 Aug TI - The impact of 3,4-methylendioxymetamphetamine (MDMA) abstinence on seeking behavior and the expression of the D(2)-like and mGlu(5) receptors in the rat brain using saturation binding analyses. LID - 10.26402/jpp.2020.4.09 [doi] AB - 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. FAU - Frankowska, M AU - Frankowska M AD - Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Drug Addiction Pharmacology, Cracow, Poland. frankow@if-pan.krakow.pl. FAU - Miszkiel, J AU - Miszkiel J AD - Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Drug Addiction Pharmacology, Cracow, Poland. FAU - Pomierny-Chamiolo, L AU - Pomierny-Chamiolo L AD - Department of Toxicology, Faculty of Pharmacy, Jagiellonian University Collegium Medicum, Cracow, Poland. FAU - Pomierny, B AU - Pomierny B AD - Department of Toxicology, Faculty of Pharmacy, Jagiellonian University Collegium Medicum, Cracow, Poland. FAU - Celeste Borelli, A AU - Celeste Borelli A AD - Department of Medical Sciences, University of Ferrara, Ferrara, Italy. FAU - Suder, A AU - Suder A AD - Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Drug Addiction Pharmacology, Cracow, Poland. FAU - Filip, M AU - Filip M AD - Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Drug Addiction Pharmacology, Cracow, Poland. LA - eng PT - Journal Article DEP - 20201212 PL - Poland TA - J Physiol Pharmacol JT - Journal of physiology and pharmacology : an official journal of the Polish Physiological Society JID - 9114501 RN - 0 (Central Nervous System Stimulants) RN - 0 (Grm5 protein, rat) RN - 0 (Receptor, Metabotropic Glutamate 5) RN - 0 (Receptors, Dopamine D2) RN - 0 (dopamine D2L receptor) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM MH - Amphetamine-Related Disorders/*metabolism/physiopathology/psychology MH - Animals MH - Behavior, Animal/*drug effects MH - Brain/*drug effects/metabolism/physiopathology MH - Central Nervous System Stimulants/*pharmacology MH - Cues MH - Drug-Seeking Behavior/*drug effects MH - Housing, Animal MH - Male MH - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology MH - Rats, Wistar MH - Receptor, Metabotropic Glutamate 5/*metabolism MH - Receptors, Dopamine D2/*metabolism MH - Social Isolation EDAT- 2020/12/15 06:00 MHDA- 2021/08/25 06:00 CRDT- 2020/12/14 20:15 PHST- 2020/08/06 00:00 [received] PHST- 2020/08/30 00:00 [accepted] PHST- 2020/12/14 20:15 [entrez] PHST- 2020/12/15 06:00 [pubmed] PHST- 2021/08/25 06:00 [medline] AID - 10.26402/jpp.2020.4.09 [doi] PST - ppublish SO - J Physiol Pharmacol. 2020 Aug;71(4). doi: 10.26402/jpp.2020.4.09. Epub 2020 Dec 12.