Prevention of relapse to methamphetamine self-administration by environmental enrichment: involvement of glucocorticoid receptors.

Autor: Nicolas C; Université de Poitiers, INSERM, U-1084, Laboratoire des Neurosciences Expérimentales et Cliniques, Poitiers, France., Hofford RS; Department of Psychology, University of Kentucky, Lexington, KY, 40536-0509, USA., Dugast E; Université de Poitiers, INSERM, U-1084, Laboratoire des Neurosciences Expérimentales et Cliniques, Poitiers, France.; CHU de Poitiers, Poitiers, France., Lardeux V; Université de Poitiers, INSERM, U-1084, Laboratoire des Neurosciences Expérimentales et Cliniques, Poitiers, France., Belujon P; Université de Poitiers, INSERM, U-1084, Laboratoire des Neurosciences Expérimentales et Cliniques, Poitiers, France., Solinas M; Université de Poitiers, INSERM, U-1084, Laboratoire des Neurosciences Expérimentales et Cliniques, Poitiers, France., Bardo MT; Department of Psychology, University of Kentucky, Lexington, KY, 40536-0509, USA., Thiriet N; Université de Poitiers, INSERM, U-1084, Laboratoire des Neurosciences Expérimentales et Cliniques, Poitiers, France. nathalie.thiriet@univ-poitiers.fr.
Jazyk: angličtina
Zdroj: Psychopharmacology [Psychopharmacology (Berl)] 2022 Apr; Vol. 239 (4), pp. 1009-1018. Date of Electronic Publication: 2021 Mar 25.
DOI: 10.1007/s00213-021-05770-6
Abstrakt: Rationale: In rodents, environmental enrichment (EE) produces both preventive and curative effects on drug addiction, and this effect is believed to depend at least in part on EE's actions on the stress system.
Objectives: This study investigated whether exposure to EE during abstinence reduces methamphetamine seeking after extended self-administration. In addition, we investigated whether these effects are associated with alterations in the levels of glucocorticoid receptors (GR) in the brain and whether administration of GR antagonists blocks methamphetamine relapse.
Methods: We allowed rats to self-administer methamphetamine for twenty 14-h sessions. After 3 weeks of abstinence either in standard (SE) or EE conditions, we measured methamphetamine seeking in a single 3-h session. Then, we used western blot techniques to measure GR levels in several brain areas. Finally, in an independent group of rats, after methamphetamine self-administration and abstinence in SE, we administered the GR antagonist mifepristone, and we investigated methamphetamine seeking.
Results: Exposure to EE reduced methamphetamine seeking and reversed methamphetamine-induced increases in GR levels in the ventral and dorsal hippocampus. In addition, EE decreased GR levels in the amygdala in drug-naive animals, but this effect was prevented by previous exposure to methamphetamine. Administration of mifepristone significantly decreased methamphetamine seeking.
Conclusions: The anti-craving effects of EE are paralleled by restoration of methamphetamine-induced dysregulation of GR in the hippocampus. These results provide support for the hypothesis that the effect of EE on methamphetamine relapse is at least in part mediated by EE's action on the brain stress system.
(© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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