Cocaine- and amphetamine-regulated transcript peptide promotes reward seeking behavior in socially isolated rats.

Abstract:

:Reward deficit, expressed as anhedonia, is one of the major symptoms associated with neuropsychiatric disorders, but the underlying maladaptations have not been understood. Herein, we test the hypothesis that the neuropeptide cocaine- and amphetamine-regulated transcript (CART) may participate in the process. The study is justified since the peptide is a major player in inducing satiety and also processing of reward. The rats were socially isolated to induce reward deficit and conditioned to self-stimulate via an electrode in lateral hypothalamus (LH)-medial forebrain bundle (MFB) region. Compared to group-housed control rats, the socially isolated animals showed decreased lever press activity and elevated ICSS threshold indicating anhedonia-like condition. However, the effects of social isolation were alleviated by CART administered via intracerebroventricular route. The changes in the expression of CART protein and mRNA were screened using immunofluorescence and qRT-PCR methods, respectively. Socially isolated rats showed reduction in the expression of CART in the LH, nucleus accumbens shell (AcbSh) and posterior ventral tegmental area (pVTA) and CART mRNA in the Acb and LH. Double immunostaining with antibodies against CART and synaptophysin revealed significant loss of colabeled elements in LH, AcbSh and pVTA. We suggest that down-regulation of endogenous CARTergic system in the LH-pVTA-AcbSh reward circuitry may be causal to motivational anhedonia like phenotype seen in neuropsychiatric conditions.

journal_name

Brain Res

journal_title

Brain research

authors

Somalwar AR,Choudhary AG,Balasubramanian N,Sakharkar AJ,Subhedar NK,Kokare DM

doi

10.1016/j.brainres.2019.146595

subject

Has Abstract

pub_date

2020-02-01 00:00:00

pages

146595

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(19)30649-3

journal_volume

1728

pub_type

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