Peer-induced cocaine seeking in rats: Comparison to nonsocial stimuli and role of paraventricular hypothalamic oxytocin neurons

Lindsey R. Hammerslag, Bree A. Humburg, Samantha G. Malone, Joshua Beckmann, Kathryn E. Saatman, Valery Grinevich, Michael T. Bardo

Research output: Contribution to journalArticlepeer-review

Abstract

The purpose of this study was to determine if social vs nonsocial cues (peer vs light/tone) can serve as discriminative stimuli to reinstate cocaine seeking. In addition, to assess a potential mechanism, an oxytocin (OT) promoter-linked hM3Dq DREADD was infused into the paraventricular nucleus of the hypothalamus to determine whether peer-induced cocaine seeking is decreased by activation of OT neurons. Male rats underwent twice-daily self-administration sessions, once with cocaine in the presence of one peer (S+) and once with saline in the presence of a different peer (S−). Another experiment used similar procedures, except the discriminative stimuli were nonsocial (constant vs flashing light/tone), with one stimulus paired with cocaine (S+) and the other paired with saline (S−). A third experiment injected male and female rats with OTp-hM3Dq DREADD or control virus into PVN and tested them for peer-induced reinstatement of cocaine seeking following clozapine (0.1 mg/kg). Although acquisition of cocaine self-administration was similar in rats trained with either peer or light/tone discriminative stimuli, the latency to first response was reduced by the peer S+, but not by the light/tone S+. In addition, the effect of the conditioned stimulus was overshadowed by the peer S+ but not by the light/tone S+. Clozapine blocked the effect of the peer S+ in rats receiving the OTp-hM3Dq DREADD virus, but not in rats receiving the control virus. These results demonstrate that a social peer can serve as potent trigger for drug seeking and that OT in PVN modulates peer-induced reinstatement of cocaine seeking.

Original languageEnglish
Article numbere13217
JournalAddiction Biology
Volume27
Issue number5
DOIs
StatePublished - Sep 2022

Bibliographical note

Funding Information:
The authors would like to thank Emily Denehy and Diego Benusiglio for their expert technical assistance. In addition, they thank Dr. Yavin Shaham for his helpful feedback during the early stages of these experiments. This work was supported by the National Institute on Drug Abuse grants T32 DA16176 (for LRH) and R21 DA041755 (to MTB) and the Deutsche Forschungsgemeinschaft grants GR 3619/13‐1, GR 3619/15‐1, GR 3619/16‐1, and the SFB Consortium 1158‐2 (to VG).

Publisher Copyright:
© 2022 Society for the Study of Addiction.

Keywords

  • cocaine
  • oxytocin
  • self-administration
  • social peer

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology
  • Psychiatry and Mental health

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