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Influence of reconsolidation in maintenance of cocaine-associated contextual memories formed during adolescence or adulthood.

ABSTRACT: Adolescents are at increased risk to develop substance use disorders and suffer from relapse throughout life. Targeted weakening of drug-associated memories has been shown to reduce relapse-like behavior in adult rats, however this process has been understudied in adolescents. We aimed to examine whether adolescent-formed, cocaine-associated memories could be manipulated via reconsolidation mechanisms. To accomplish this objective, we used an abbreviated operant cocaine self-administration paradigm (ABRV Coc-SA). Adult and adolescent rats received jugular catheterization surgery followed by ABRV Coc-SA in a distinct context for 2 h, 2×/day over 5 days. Extinction training (EXT) occurred in a second context for 2 h, 2×/day over 4 days. To retrieve cocaine-context memories, rats were exposed to the cocaine-paired context for 15 min, followed by subcutaneous injection of vehicle or the protein synthesis inhibitor cycloheximide (2.5 mg/kg). Two additional EXT sessions were conducted before a 2 h reinstatement test in the cocaine-paired context to assess cocaine-seeking behavior. We find that both adult and adolescent cocaine-exposed rats show similar levels of cocaine-seeking behavior regardless of post-reactivation treatment. Our results suggest that systemic treatment with the protein synthesis inhibitor cycloheximide does not impair reconsolidation of cocaine-context memories and subsequent relapse during adulthood or adolescence.

SUBMITTER: Charpentier ANH

PROVIDER: S-EPMC10457301 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Influence of reconsolidation in maintenance of cocaine-associated contextual memories formed during adolescence or adulthood.

Charpentier André N Herrera ANH Olekanma Doris I DI Valade Christian T CT Reeves Christopher A CA Cho Bo Ram BR Arguello Amy A AA

Scientific reports 20230825 1

Adolescents are at increased risk to develop substance use disorders and suffer from relapse throughout life. Targeted weakening of drug-associated memories has been shown to reduce relapse-like behavior in adult rats, however this process has been understudied in adolescents. We aimed to examine whether adolescent-formed, cocaine-associated memories could be manipulated via reconsolidation mechanisms. To accomplish this objective, we used an abbreviated operant cocaine self-administration parad ...[more]

PMID: 37626103

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Project description:ImportanceThe prescribing of stimulant medications for attention-deficit/hyperactivity disorder (ADHD) has increased in the US. Prescription stimulants are one of the most commonly misused controlled substances during adolescence. Despite a 10-fold increase in stimulant-related overdose deaths in the past decade, the transitions from prescription stimulants to illicit stimulants (eg, cocaine, methamphetamine) remain relatively unknown in longitudinal population-based studies.ObjectiveTo determine the longitudinal transitions from adolescents' prescription stimulant exposure (ie, stimulant therapy for ADHD and prescription stimulant misuse [PSM]) to later cocaine and methamphetamine use during young adulthood.Design, setting, and participantsNational longitudinal multicohort panels of US 12th grade public and private school students in the coterminous US were assessed annually (baseline cohort years 2005-2017 [between March and June]) and followed up across 3 waves over a 6-year period to 23 to 24 years of age (follow-up years 2011-2021 [between April and October]).ExposureHistory of self-reported stimulant therapy for ADHD at baseline.Main outcomes and measuresIncidence and prevalence of past-year use of cocaine and methamphetamine during young adulthood (19-24 years of age).ResultsAmong 5034 students enrolled at baseline (2589 [52.0%] female), 470 (10.2% [95% CI, 9.4%-11.2%]) reported use of stimulant therapy for ADHD, 671 (14.6% [95% CI, 13.5%-15.6%]) reported PSM only, and 3459 (75.2% [95% CI, 73.9%-76.4%]) reported neither (and served as population controls). In controlled analyses, there were no statistically significant differences between adolescents who reported stimulant therapy for ADHD at baseline compared with population controls in the adjusted odds of transitioning to later cocaine or methamphetamine initiation or use during young adulthood (19-24 years of age). In contrast, PSM during adolescence in those not treated with stimulants for ADHD had significantly higher odds of transitioning to later cocaine or methamphetamine initiation and use during young adulthood compared with population controls (adjusted odds ratio, 2.64 [95% CI, 1.54-4.55]).Conclusions and relevanceIn this multicohort study, adolescents' stimulant therapy for ADHD was not associated with increased risk of later cocaine and methamphetamine use during young adulthood. Adolescents' prescription stimulant misuse offered a signal for subsequent cocaine or methamphetamine use and warrants monitoring and screening.

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Influence of reconsolidation in maintenance of cocaine-associated contextual memories formed during adolescence or adulthood.

Publications

Influence of reconsolidation in maintenance of cocaine-associated contextual memories formed during adolescence or adulthood.

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