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

Sci Rep. 2023 Aug 25;13(1):13936. doi: 10.1038/s41598-023-39949-y.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Catheterization, Central Venous*
  • Cocaine* / pharmacology
  • Cycloheximide
  • Protein Synthesis Inhibitors
  • Rats

Substances

  • Cycloheximide
  • Protein Synthesis Inhibitors
  • Cocaine