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Originally studied for its role in energy homeostasis, the paraventricular nucleus of the thalamus (PVT) has recently gained attention because of its involvement in the modulation of drug-directed behavior. The posterior part of the PVT (pPVT) is connected with brain structures that modulate motivated behavior, and we tested whether the pPVT plays a pivotal role in cocaine seeking. The aim of the present study was to investigate whether transient inactivation of the pPVT prevents cue-induced reinstatement of cocaine seeking but not natural reward seeking. Male Wistar rats were trained to associate a discriminative stimulus (S + ) with the availability of cocaine or a highly palatable conventional reinforcer, sweetened condensed milk (SCM). Following extinction, the cocaine S + and SCM S + elicited comparable levels of reinstatement. Intra-pPVT administration of the γ-aminobutyric acid-A (GABA A ) and GABA B receptor agonists muscimol and baclofen (0.06 and 0.6 mM, respectively) prior to the presentation of the cocaine or SCM S + completely prevented the reinstatement of cocaine seeking, with no statistically significant effects on SCM seeking. These data show that the pPVT plays an important role in neuronal mechanisms that drive cocaine-seeking behavior. [ABSTRACT FROM AUTHOR]