1 Department of Psychology, Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Quebec, Canada.
2 Department of Health Kinesiology, and Applied Physiology, Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Quebec, Canada.

Abstinence from drug use is often the result of the associated negative consequences. However, relapse occurs in a large proportion of abstinent users, and the underlying brain mechanisms are not clear. An arguably relevant brain area is the posterior paraventricular nucleus of the thalamus (pPVT), which plays a role in motivational processes and addiction-like behaviours. Using a punishment-imposed abstinence procedure, we assessed the effect of chemogenetic inhibition and excitation of the pPVT on food deprivation-induced relapse to heroin-seeking in male and female rats. Rats were trained to self-administer heroin (0.1 mg/kg/infusion) for 2 weeks under a seeking-taking chain schedule. For punishment-imposed abstinence, a mild footshock (0.2 to 0.6 mA) was delivered on 30% of the completed seek lever links instead of access to the take lever. Relapse to heroin-seeking was tested after 24 h of food deprivation and under sated condition. Animals were injected (i.p.) with either a DREADD ligand or vehicle 15-20 min before the tests. There was no sex difference in heroin self-administration or punishment-imposed abstinence. Under the food deprivation condition, chemogenetic inhibition of the pPVT increased heroin-seeking compared to the control group, only in male rats. Chemogenetic excitation of the pPVT resulted in an increase in heroin-seeking under food deprivation conditions. Our results support an involvement of the pPVT in relapse to heroin-seeking and suggest a sex-dependent effect.