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
This study aimed 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.
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Acknowledgements
We would like to thank Drs. Jonathan Morrow, Aram Parsegian, and Joshua Haight for their feedback on a previous version of this manuscript. We would also like to thank Drs. Brady West and Corey Powell from the Consulting for Statistics, Computing and Analytics Research team at the University of Michigan for their helpful input on statistical modeling for portions of the data. The experiments were designed by BNK and SBF and conducted by BNK, MSK, IRC, and PC. Data was analyzed by BNK, and BNK and SBF wrote the manuscript.
Funding
Funding for this work was provided by the National Institute on Drug Abuse branch of the National Institutes of Health (RO1DA038599) awarded to SBF and training grants T32DA007821 (BNK) and T32DA007268 (IRC).
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Kuhn, B.N., Klumpner, M.S., Covelo, I.R. et al. Transient inactivation of the paraventricular nucleus of the thalamus enhances cue-induced reinstatement in goal-trackers, but not sign-trackers. Psychopharmacology 235, 999–1014 (2018). https://doi.org/10.1007/s00213-017-4816-1
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DOI: https://doi.org/10.1007/s00213-017-4816-1