Cocaine- and Amphetamine-Regulated Transcript CART Signaling within the Paraventricular Thalamus Modulates Cocaine-Seeking BehaviourReport as inadecuate




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Background

Cocaine- and amphetamine-regulated transcript CART has been demonstrated to play a role in regulating the rewarding and reinforcing effects of various drugs of abuse. A recent study demonstrated that i.c.v. administration of CART negatively modulates reinstatement of alcohol seeking, however, the sites of action remains unclear. We investigated the paraventricular thalamus PVT as a potential site of relapse-relevant CART signaling, as this region is known to receive dense innervation from CART-containing hypothalamic cells and to project to a number of regions known to be involved in mediating reinstatement, including the nucleus accumbens NAC, medial prefrontal cortex mPFC and basolateral amygdala BLA.

Methodology-Principal Findings

Male rats were trained to self-administer cocaine before being extinguished to a set criterion. One day following extinction, animals received intra-PVT infusions of saline, tetrodotoxin TTX; 2.5 ng, CART 0.625 µg or 2.5 µg or no injection, followed by a cocaine prime 10 mg-kg, i.p

Animals were then tested under extinction conditions for one hour. Treatment with either TTX or CART resulted in a significant attenuation of drug-seeking behaviour following cocaine-prime, with the 2.5 µg dose of CART having the greatest effect. This effect was specific to the PVT region, as misplaced injections of both TTX and CART resulted in responding that was identical to controls.

Conclusions-Significance

We show for the first time that CART signaling within the PVT acts to inhibit drug-primed reinstatement of cocaine seeking behaviour, presumably by negatively modulating PVT efferents that are important for drug seeking, including the NAC, mPFC and BLA. In this way, we identify a possible target for future pharmacological interventions designed to suppress drug seeking.



Author: Morgan H. James, Janine L. Charnley, Emma Jones, Emily M. Levi, Jiann Wei Yeoh, Jamie R. Flynn, Douglas W. Smith, Christopher V.

Source: http://plos.srce.hr/



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