Elsevier

Neuroscience

Volume 199, 29 December 2011, Pages 235-242
Neuroscience

Cognitive, Behavioral, and Systems Neuroscience
Research Paper
Propensity to ‘relapse’ following exposure to cocaine cues is associated with the recruitment of specific thalamic and epithalamic nuclei

https://doi.org/10.1016/j.neuroscience.2011.09.047Get rights and content

Abstract

The thalamus is considered an important interface between the ventral striatopallidum and the dorsal striatum, and may therefore contribute to compulsive drug-seeking behaviour. Recent evidence suggests that the paraventricular thalamus (PVT), a dorsal midline thalamic nucleus, and the mediodorsal thalamus (MD) are involved in drug self-administration and respond to drug-associated cues. At present, however, the role of these thalamic regions in mediating cue-induced reinstatement of cocaine-seeking is unclear. Similarly, the habenula complex, part of the epithalamus, has been implicated in nicotine self-administration and cue-induced reinstatement of heroin seeking, but the role of this region in cocaine reinstatement behaviour has received little attention. Rats (n=20) were trained to self-administer cocaine in the presence of discriminative stimuli associated with drug availability (S+) or drug non-availability (S). Once a stable level of responding was reached, lever pressing was extinguished. Animals were then tested for reinstatement and sacrificed immediately following the presentation of either the S or S+ discriminative stimuli, and Fos-protein expression was assessed in thalamic and epithalamic regions. Interestingly, significant variation was observed in reinstatement behaviour, allowing a comparison between high-reinstating (HR), low-reinstating (LR) and control animals. Compared with LR animals, HR animals exhibited increased Fos-protein expression in the PVT, intermediodorsal thalamus and the medial and lateral divisions of the habenula. Our data provide evidence that activation of thalamic and epithalamic nuclei is associated with propensity to reinstate to cocaine-seeking elicited by drug-related cues. We also build upon existing data highlighting the importance of the PVT in reinstatement behaviour.

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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