Chemogenetic inhibition reveals midline thalamic nuclei and thalamo‐accumbens projections mediate cocaine‐seeking in rats. (26th July 2017)

• Record Type: Journal Article
• Authors: Wunsch, Amanda M.; Yager, Lindsay M.; Donckels, Elizabeth A.; Le, Calvin T.; Neumaier, John F.; Ferguson, Susan M.
• Is Part Of: European journal of neuroscience. Volume 46:Number 3(2017)
• Page Start: 1850
• Page End: 1862
• Publication Date: 2017-07-26
• Subjects: addiction -- cocaine -- DREADDs -- neural circuits -- rat; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.13631
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: Drug addiction is a chronic disease that is shaped by alterations in neuronal function within the cortical–basal ganglia‐thalamic circuit. However, our understanding of how this circuit regulates drug‐seeking remains incomplete, and relapse rates remain high. The midline thalamic nuclei are an integral component of the cortical–basal ganglia‐thalamic circuit and are poised to mediate addiction behaviors, including relapse. It is surprising that little research has examined the contribution of midline thalamic nuclei and their efferent projections in relapse. To address this, we expressed inhibitory, Gi/o ‐coupled DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) in a subset of the midline thalamic nuclei or in midline thalamic nuclei neurons projecting to either the nucleus accumbens or the amygdala. We examined the effect of transiently decreasing activity of these neuronal populations on cue‐induced and cocaine‐primed reinstatement of cocaine‐seeking. Reducing activity of midline thalamic nuclei neurons attenuated both cue‐induced and cocaine‐primed reinstatement, but had no effect on cue‐induced reinstatement of sucrose‐seeking or locomotor activity. Interestingly, attenuating activity of efferent projections from the anterior portion of midline thalamic nuclei to the nucleus accumbens blocked cocaine‐primed reinstatement but enhanced cue‐induced reinstatement. Decreasing activity of efferent projections from either the posterior midline thalamic nuclei to the nucleus accumbens or the midline thalamic nuclei to amygdala had no effect. These results reveal a novel contribution of subsets of midline thalamic nuclei neurons in drug‐seeking behaviors and suggest that modulation of midline thalamic nuclei activity may be a promising therapeutic target for preventing relapse. Abstract : Chemogenetic inhibition of midline thalamic nuclei (MTN) decreases both cue‐induced and cocaine‐primed reinstatement of cocaine‐seeking in rats. Inhibition of efferent projections from anterior MTN to the nucleus accumbens (NAc) has similar effects on cocaine‐primed reinstatement but enhances cue‐induced reinstatement. However, this same manipulation in efferent projections from posterior MTN to the NAc or in efferent projections to the basolateral nucleus of the amygdala (BLA) had no effect. These data suggest that modulation of MTN activity may be a promising therapeutic target for preventing relapse.