Role of adolescent-formed, context-drug-associations on reinstatement of drug-seeking behavior in rats

Abstract

Rationale

Drug use during adolescence results in a lifelong risk to develop substance-use disorders. Adolescent rats are less reactive to cocaine-associated cues compared with adults; however, the contribution of adolescent-formed, context-drug-associations to elicit relapse-like behavior is underexplored. Although it is known that social isolation can impact drug-seeking behavior, the effects of housing conditions on context-induced, cocaine-seeking during adolescence vs adulthood are unknown.

Objectives

The present study compared the effect of adolescent vs adult-formed context-drug associations under different housing conditions (pair vs single) on cocaine-seeking behavior during adolescence or adulthood. This objective was accomplished using operant cocaine self-administration (Coc-SA) under a standard, non-abbreviated (Non-ABRV) or modified abbreviated (ABRV) paradigm.

Methods

In experiment 1, adolescent and adult rats received Non-ABRV Coc-SA in a distinct context (2 h, 1×/day, 10 days), and extinction training (EXT) in a second context (1 h, 1×/day, 8 days) with reinstatement test (TEST) during adulthood in the cocaine-paired context. In experiments 2 and 3, rats received all behavioral phases during adolescence or adulthood: ABRV Coc-SA (2 h, 2×/day, 5 days), EXT (1 h, 4×/day, 2 days) with TEST in a cocaine-paired or novel, unpaired context. All experiments included pair and single-housing conditions.

Results and conclusions

Age at cocaine exposure did not influence behavior in Non-ABRV or ABRV paradigms. Under Non-ABRV conditions, adolescent and adult single-housed rats had higher seeking behavior than pair housed. These data suggest that social isolation influences context-induced, cocaine-seeking regardless of age at drug exposure and provides a condensed, ABRV paradigm to investigate context-induced, cocaine-seeking behavior during adolescence.

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Acknowledgements

The authors thank Ana Silvafarias, Chris Reeves and Chris Davlantes for excellent technical assistance.

Funding

This work was supported by NIDA grant R00 DA037271.

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Correspondence to Amy A. Arguello.

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All protocols were approved by the Institutional Animal Care and Use Committee (IACUC) at Michigan State University (MSU) and followed the National Research Council’s Guide for the Care and Use of Laboratory Rats.

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Cho, B.R., Gerena, J., Olekanma, D.I. et al. Role of adolescent-formed, context-drug-associations on reinstatement of drug-seeking behavior in rats. Psychopharmacology (2020). https://doi.org/10.1007/s00213-020-05575-z

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Keywords

  • Adolescence
  • Context
  • Self-administration
  • Cocaine seeking
  • Reinstatement
  • Isolation housing
  • Pair housing
  • Extinction