Voluntary oral methamphetamine increases memory deficits and contextual sensitization during abstinence associated with decreased PKMζ and increased κOR in the hippocampus of female mice
| Autor: | Peter A. Serrano, Tytus Andrejewski, Jorge A. Avila, Abdurrahman Aslan, Victoria N. Luine, Nicoletta Memos |
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| Přispěvatelé: | İstinye Üniversitesi, Eczacılık Fakültesi, Eczacılık Meslek Bilimleri Bölümü, Aslan, Abdurrahman |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
media_common.quotation_subject Amphetamine-Related Disorders Administration Oral Hippocampus Addiction Article Methamphetamine Kappa Opiate Receptor Mice Sex Factors medicine Animals Pharmacology (medical) Maze Learning Sex Differences Protein Kinase M Zeta Protein Kinase C Sensitization Spatial Memory media_common Pharmacology Memory Disorders Behavior Animal business.industry Receptors Opioid kappa Cognition Abstinence Mice Inbred C57BL Psychiatry and Mental health Memory Short-Term medicine.anatomical_structure Turnover Central Nervous System Stimulants Female business Neuroscience medicine.drug |
| Zdroj: | J Psychopharmacol |
| Popis: | Background: Female populations exhibit vulnerabilities to psychostimulant addiction, as well as cognitive dysfunction following bouts of abuse. Aims: The goal for this study was to advance our understanding of the mechanisms that produce sex disparities in drug addiction. Methods: We used an animal model for voluntary oral methamphetamine administration (VOMA) and focused on male and female mice that consumed 7.6–8.2 mg/kg of methamphetamine (MA) per day during the last 18 days of the paradigm. Results: The VOMA-exposed female mice displayed increased locomotor activity in the drug-administration context compared to male mice, demonstrating sex-specific changes in contextual sensitization. During 2 weeks of forced abstinence, mice underwent further behavioral testing. We show that abstinence increased open-arm entries on the elevated plus maze in both sexes. There were no differences in immobility on the tail suspension test. In a hippocampal-dependent radial arm maze task, VOMA-treated female mice, but not male mice, showed working memory deficits. Hippocampal tissue was collected and analyzed using Western blotting. VOMA-exposed female mice exhibited increased kappa opioid receptor (κOR) expression in the hippocampus compared to male mice, suggesting a vulnerability toward abstinence-induced dysphoria. Female VOMA mice also exhibited a decrease in the memory protein marker, protein kinase M zeta (PKMζ), in the hippocampus. Conclusions: Our study reveals sex-specific effects following abstinence from chronic MA consumption on hippocampal κOR and PKMζ expression, suggesting that these neural changes in female mice may underlie spatial memory deficits and identify an increased susceptibility to dysregulated neural mechanisms. These data validate VOMA as a model sensitive to sex differences in behavior and hippocampal neurochemistry following chronic MA exposure. |
| Databáze: | OpenAIRE |
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