Transient inactivation of the paraventricular nucleus of the thalamus enhances cue-induced reinstatement in goal-trackers, but not sign-trackers

Abstract

Rationale The paraventricular nucleus of the thalamus (PVT) has been shown to mediate cue-motivated behaviors, such as sign- and goal-tracking, as well as reinstatement of drug-seeking behavior. However, the role of the PVT in mediating individual variation in cue-induced drug-seeking behavior remains unknown. Objectives To determine if inactivation of the PVT differentially mediates cue-induced drug-seeking behavior in sign-trackers and goal-trackers. Methods Rats were characterized as sign-trackers (STs) or goal-trackers (GTs) based on their Pavlovian conditioned approach behavior. Rats were then exposed to 15 days of cocaine self-administration, followed by a 2-week forced abstinence period and then extinction training. Rats then underwent tests for cue-induced reinstatement and general locomotor activity, prior to which they received an infusion of either saline (control) or baclofen/muscimol (B/M) to inactivate the PVT. Results Relative to control animals of the same phenotype, GTs show a robust increase in cue-induced drug-seeking behavior following PVT inactivation, whereas the behavior of STs was not affected. PVT inactivation did not affect locomotor activity in either phenotype. Conclusion In GTs, the PVT appears to inhibit the expression of drug seeking, presumably by attenuating the incentive value of the drug cue. Thus, inactivation of the PVT releases this inhibition in GTs, resulting in an increase in cue-induced drug-seeking behavior. PVT inactivation did not affect cue-induced drug-seeking behavior in STs, suggesting that the role of the PVT in encoding the incentive motivational value of drug cues differs between STs and GTs.

The role of the paraventricular nucleus of the thalamus in the augmentation of heroin seeking induced by chronic food restriction

“…Inhibition of PVT activity, then, may "unmask" this suppressed incentive value. 43 Our findings are in agreement with this theory. It is possible, although not directly assessed by Kuhn et al, 43 that activation of the PVT would robustly act to suppress a conditioned incentive value that was previously acquired (ie, during the heroin self-administration training), resulting in the attenuation of cue-induced heroin seeking.…”

“…31 Similarly, combined inactivation of aPVT and pPVT augmented cue-induced reinstatement of extinguished cocaine seeking, but specifically in "goal tracking" rats, with no significant effects on reinstatement in "sign tracking" rats. 43 Unfortunately, the effects of PVT activation on drug seeking were not assessed in any of the studies cited above.…”

“…As mentioned above, the neural mechanisms underlying reinstatement of extinguished drug seeking are different from those that underlie drug seeking following a period of withdrawal. 16,17 Recently, Flagel and colleagues 43,46,47 suggested that the PVT is important for the process of attributing incentive salience to rewardassociated cues. Thus, at least in a subset of individuals, the PVT may act to "hide" the learned incentive value of a conditioned cue.…”

The Paraventricular Thalamus is a Critical Mediator of Top-down Control of Cue-motivated Behavior in Rats

“…The PVT has, in fact, come to be known as the "thalamic gateway" 33 for appetitive motivation; acting to integrate cognitive, emotional, motivational and viscerosensitive information, and, in turn, guide behavioral responses 33,34 . Consistent with this view, the PVT has been implicated in the propensity to attribute incentive motivational value to reward-cues [35][36][37] .The functional connectivity of the PVT in response to cue-induced neuronal activity differentiates STs from GTs 28,29,35 . In STs, cue-induced activity in the PVT is correlated with activity in subcortical areas, including the nucleus accumbens (NAc); whereas in GTs, cue-induced activity in the PVT is correlated with activity in the prelimbic cortex (PrL) 28,35 .…”

“…The PVT has, in fact, come to be known as the "thalamic gateway" 33 for appetitive motivation; acting to integrate cognitive, emotional, motivational and viscerosensitive information, and, in turn, guide behavioral responses 33,34 . Consistent with this view, the PVT has been implicated in the propensity to attribute incentive motivational value to reward-cues [35][36][37] .…”