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 S. Beckmann; Kathryn E. Saatman; Valery Grinevich; Michael T. Bardo

doi:10.1111/adb.13217

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 S. Beckmann
, Kathryn E. Saatman
, Valery Grinevich
, Michael T. Bardo

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

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 language	English
Article number	e13217
Journal	Addiction Biology
Volume	27
Issue number	5
DOIs	https://doi.org/10.1111/adb.13217
State	Published - Sep 2022

Bibliographical note

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

Funding

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). LRH, JSB and MTB were responsible for the study concept and design. LRH, BAH and SGM contributed to the acquisition of behavioural and immunohistochemical data. VG was responsible for supplying the virus and providing advice on its use. KES provided critical direction on conducting the immunohistochemical assays and imaging with confocal microscopy. LRH conducted the data analysis, and LRH and MTB were involved in interpretation of findings. LRH drafted the manuscript, and MTB provided critical revision of the manuscript for important intellectual content. All authors approved the final version for publication. 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).

Funders

Funder number

Deutsche Forschungsgemeinschaft

GR 3619/15‐1, GR 3619/16‐1, GR 3619/13‐1

Author National Institute on Drug Abuse DA031791 Mark J Ferris National Institute on Drug Abuse DA006634 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA026117 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA028162 Elizabeth G Pitts National Institute of General Medical Sciences GM102773 Elizabeth G Pitts Peter McManus Charitable Trust Mark J Ferris National Institute on Drug Abuse

T32DA016176, R21DA041755, F31DA057050

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

cocaine
oxytocin
self-administration
social peer

ASJC Scopus subject areas

Medicine (miscellaneous)
Pharmacology
Psychiatry and Mental health

Access to Document

10.1111/adb.13217

Cite this

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

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",

author = "Hammerslag, \{Lindsey R.\} and Humburg, \{Bree A.\} and Malone, \{Samantha G.\} and Beckmann, \{Joshua S.\} and Saatman, \{Kathryn E.\} and Valery Grinevich and Bardo, \{Michael T.\}",

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doi = "10.1111/adb.13217",

language = "English",

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AU - Hammerslag, Lindsey R.

AU - Humburg, Bree A.

AU - Malone, Samantha G.

AU - Beckmann, Joshua S.

AU - Saatman, Kathryn E.

AU - Grinevich, Valery

AU - Bardo, Michael T.

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N2 - 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.

AB - 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.

KW - cocaine

KW - oxytocin

KW - self-administration

KW - social peer

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UR - https://www.scopus.com/pages/publications/85136563343#tab=citedBy

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SN - 1355-6215

VL - 27

JO - Addiction Biology

JF - Addiction Biology

IS - 5

M1 - e13217

ER -

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

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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