Cognitive, Behavioral, and Systems NeuroscienceResearch PaperPropensity to ‘relapse’ following exposure to cocaine cues is associated with the recruitment of specific thalamic and epithalamic nuclei
Highlights
▶Animals exhibit variability in reinstatement following exposure to cocaine cues. ▶High-reinstating animals exhibit increased Fos expression in the PVT. ▶Activation of PVT is positively correlated with relapse. ▶Increased Fos expression also observed in other thalamic and habenula regions.
Section snippets
Subjects
Male Sprague–Dawley rats (Central Animal House, University of Newcastle, NSW, Australia; weighing 200–250 g upon arrival) were housed two per cage on a reverse 12-h light/dark cycle (lights off at 7:00 am) with ad libitum access to food and water. All procedures were performed in accordance with protocols approved by the University of Newcastle Animal Care and Ethics Committee, New South Wales Animal Research Act.
Drugs
For cocaine self-administration, cocaine hydrochloride (Johnson Matthey,
Self-administration training, conditioning and reinstatement
All rats developed stable responding (±10% over three sessions) for cocaine after 8.5±1.4 (mean±SEM) days of training. During conditioning, the number of self-administered infusions was significantly higher (t[19]=−9.669, P<.001) for cocaine compared with saline (Fig. 2a). After conditioning, animals underwent extinction training with the extinction criterion being met after 22.3±3.7 (mean±SEM) days. Total group data indicated that re-exposure to the cocaine-linked S+ produced a significant
Discussion
Recent reports have highlighted the importance of studying individual differences in addiction and relapse vulnerability (Belin et al., 2009, Brown et al., 2011. Therefore, in the present study we have taken a novel approach to characterizing the cocaine cue-induced recruitment patterns of thalamic and epithalamic nuclei. We exploited our observation that in a cohort of cocaine self-administering animals, significant variability in reinstatement (relapse-like) behaviour in response to a
Conclusion
In summary, we show that re-exposure to cocaine-associated cues is associated with increased Fos-protein expression in thalamic and epithalamic nuclei. Furthermore, by examining individual differences in relapse propensity, we show that Fos expression within dorsal midline thalamic nuclei (PVT and IMD) and the habenula is significantly greater in high- versus low-reinstating animals. Our findings build on existing literature implicating the PVT in reinstatement behaviour by showing that
Acknowledgments
This work was supported by project grants from the National Health and Medical Research Council of Australia and the Hunter Medical Research Institute to C.V.D. We would like to thank Mr. Jiann Wei Yeoh and Ms. Emily Levi for their technical assistance.
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2021, NeuropharmacologyCitation Excerpt :Using these various paradigms, a handful of studies have examined the role of the PVT in the reinstatement of alcohol and drug-related behaviors using c-Fos activation and/or behavioral pharmacology measures. The PVT has been shown to exhibit increased c-Fos activation following cue-induced reinstatement of both alcohol (Dayas et al., 2008) and cocaine (James, Charnley, Flynn, et al., 2011; Matzeu et al., 2017) seeking behavior. Moreover, transient inactivation of the PVT (via intra-PVT microinjections of baclofen/muscimol) blocks cocaine cue-induced reinstatement behavior (Matzeu et al., 2015).
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2021, Neuroscience and Biobehavioral ReviewsCitation Excerpt :PVT neurons express a variety of receptors including for corticotropin-releasing hormone, opioids, dopamine, neuropeptide S, VIP, and cannabinoid, among others (Colavito et al., 2015; Kirouac, 2015). PVT has been implicated in a diverse range of functions including arousal (Colavito et al., 2015), stress (Bhatnagar, 2003; Bhatnagar and Dallman, 1999; Bhatnagar et al., 2002; Hsu et al., 2014), fear (Beas et al., 2018; Do-Monte et al., 2015; Penzo et al., 2015; Zhu et al., 2018), appetitive learning (Otis et al., 2017, 2019; Zhu et al., 2018), incentive salience (Campus et al., 2019; Haight and Flagel, 2014; Haight et al., 2015, 2017), relapse to drug seeking (Dayas et al., 2007, 2008; Hamlin et al., 2009; James et al., 2011, 2010; James and Dayas, 2013; Marchant et al., 2010; Martin-Fardon and Boutrel, 2012; Matzeu et al., 2017, 2015), opiate withdrawal (Zhu et al., 2016), drinking and feeding (Barson et al., 2015; Ong et al., 2017). We suggest that PVT is implicated in these diverse functions because they each have in common the need for bistable selection as they involve competing motivational demands on the animal and PVT is a key component of the circuitry for this selection.