Restoration of prosocial behavior in rats after heroin self-administration via chemogenetic activation of the anterior insular cortex

ABSTRACT

The anterior insular cortex (AIC) mediates various social, emotional, and interoceptive components of addiction. We recently demonstrated a disruption of prosocial behavior following heroin self-administration in rats, as assessed by examining the animals’ propensity to rescue its cagemate from a plastic restrainer while having simultaneous access to heroin. To examine the possibility that heroin-induced deficits in prosocial function are mediated by the AIC, the present study examined the effects of chemogenetic activation or inhibition of excitatory AIC pyramidal neurons on heroin-induced prosocial deficits. After establishment of baseline rescuing behavior, rats received bilateral infusions of viral vectors encoding either a control virus (AAV-CaMKIIα-GFP), stimulatory DREADD (AAV-CaMKIIα-hM3Dq-mCherry) (Experiment 1), or inhibitory DREADD (AAV-CaMKIIα-hM4Di-mCherry) (Experiment 2), into the AIC. Rats were then allowed to self-administer heroin (0.06 mg/kg/infusion) 6 hr/day for 2 weeks. Prior to re-assessment of prosocial behavior, animals were administered clozapine-N-oxide (1.5 mg/kg, i.p.) to assess the effects of chemogenetic activation or inhibition of the AIC. Relative to control animals, chemogenetic activation of the AIC reversed deficits in rescuing behavior induced by heroin, whereas chemogenetic inhibition of the AIC had no effect. We hypothesize that stimulatory neuromodulation of the AIC may be a novel approach for restoring prosociality in opiate abuse.

KEYWORDS:

• Heroin
• rescue behavior
• rodent
• self-administration
• chemogenetics
• insula

Acknowledgments

This work was supported by Public Health Service grant DA042172 to MFO, a research grant award to SET from The American Psychological Association, Society of Addiction Psychology, Division 50, and funds from the College of Liberal Arts and Sciences at Arizona State University. The authors would like to acknowledge Matt Zucker, Kyle Backman, Kylie Snow, Vince Carfagno, and Leanna Monahan, for their laboratory assistance, and Mark Namba for his surgical assistance.

Disclosure statement

The authors report no conflict of interest of any kind, including the funding agencies that supported this work (NIH Public Health Service grant DA042172, American Psychological Association, and the College of Liberal Arts and Sciences at Arizona State University)

Additional information

Funding

This work was supported by the Arizona State University; National Institute on Drug Abuse [DA042172]; Society of Addiction Psychology.