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

Addict Biol. 2022 Sep;27(5):e13217. doi: 10.1111/adb.13217.

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.

Keywords: cocaine; oxytocin; self-administration; social peer.

Publication types

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

MeSH terms

  • Animals
  • Clozapine* / pharmacology
  • Cocaine* / pharmacology
  • Cocaine-Related Disorders*
  • Cues
  • Extinction, Psychological
  • Female
  • Male
  • Neurons
  • Oxytocin / pharmacology
  • Paraventricular Hypothalamic Nucleus
  • Rats
  • Self Administration

Substances

  • Oxytocin
  • Cocaine
  • Clozapine
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