Involvement of cocaine- and amphetamine-regulated transcript peptide in the hyperphagic and body weight promoting effects of allopregnanolone in rats.
Allopregnanolone (ALLO), a gamma-aminobutyric acid (GABA) type A receptor active neurosteroid, elicits hyperphagic response in rodents. Since GABA-A receptors are present on the peptidergic neurons in the hypothalamus, we were interested in finding out if ALLO and neuropeptide cocaine- and amphetamine-regulated transcript (CART) interact and influence feeding behavior. While subcutaneous ALLO treatment, for a period of 7 days, produced a significant increase in food intake and body weight, pretreatment with subthreshold dose of CART (intracerebroventricular) attenuated both the effects. On the other hand, subcutaneous administration of dehydroepiandrosterone sulfate (DHEAS; GABA-A inhibitor neurosteroid) for a period of 7 days resulted in a significant reduction in food intake and body weight. These effects of DHEAS were potentiated by intracerebroventricular pretreatment with subeffective dose of CART. The brains of ALLO-treated rats were processed for the immunohistochemical analysis of CART immunoreactive elements. ALLO treatment resulted in a significant reduction in CART immunoreactivity in the hypothalamic arcuate, paraventricular and lateral nuclei, and nucleus accumbens shell. The results of the present study suggest that ALLO and CART might interact in the brain, and influence food intake and body weight. However, further investigations are needed to clarify the precise mechanisms by which ALLO modulate feeding behavior.
Rungta College of Pharmaceutical Sciences and Research, Rungta Educational Campus, Kohka-Kurud Road, Bhilai 490024, Chhattisgarh, India.
Kartik T
KT
Nakhate
Nishikant K
NK
Subhedar
Ashish P
AP
Bharne
Praful S
PS
Singru
Dadasaheb M
DM
Kokare
D000818:Animals; D004435:Eating / Q000187:drug effects*; D006963:Hyperphagia / Q000139:chemically induced; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000378:metabolism; D011280:Pregnanolone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain / Q000187:drug effects*; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D009419:Nerve Tissue Proteins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D011280:Pregnanolone
Allopregnanolone; Body weight; CART; Food intake