The Role of the Posterior Paraventricular Nucleus of the Thalamus in Food Deprivation-Induced Heroin-Seeking Relapse, in Male and Female Rats.

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.