Pretreatment with a CRF antagonist amplifies feeding inhibition induced by fourth ventricular cocaine- and amphetamine-regulated transcript peptide

Timothy H Moran,Ulrika Smedh,Karen A Scott

doi:10.1186/s12868-019-0494-8

Abstract

BackgroundPre-treatment with the corticotropin-releasing factor antagonist α-helical CRF9-41 prevents inhibition of gastric emptying by cocaine-and amphetamine-regulated transcript peptide at a dorsal hindbrain level, but its inhibition of sucrose intake is not affected. This is suggestive of separable underlying mechanisms of action in the caudal brainstem for cocaine-and amphetamine-regulated transcript peptide with regard to food intake and gastrointestinal functions. Here we further examine cocaine-and amphetamine-regulated transcript peptide—corticotropin-releasing factor receptor interactions in caudal brainstem controls of solid food intake. Injections of combinations of vehicle, cocaine-and amphetamine-regulated transcript peptide (0.5 μg or 1 μg) or α-helical CRF9-41 were given into the fourth cerebral ventricle of rats. Nocturnal solid food intake was recorded over 22 h.ResultsPre-treatment with α-helical CRF9-41 into the fourth ventricle significantly increased the responsivity to cocaine-and amphetamine-regulated transcript peptide on hypophagia. In a separate control experiment, α-helical CRF9-41 pre-treatment blocked CRF-induced food intake inhibition indicative of its antagonistic effectiveness.ConclusionsWe conclude that an endogenous Corticotropin-releasing factor agonist may modulate suppression of food intake caused by cocaine-and amphetamine-regulated transcript peptide at a dorsal hindbrain level in the absence of stress. A potential caudal brainstem mechanism whereby cocaine-and amphetamine-regulated transcript peptide effects on food intake is attenuated via corticotropin-releasing factor receptor activity causing tonic inhibition, is suggested.

Highlights

Pre-treatment with the corticotropin-releasing factor antagonist α-helical CRF9-41 prevents inhibition of gastric emptying by cocaine-and amphetamine-regulated transcript peptide at a dorsal hindbrain level, but its inhibition of sucrose intake is not affected
Based on the observations that fourth i.c.v. or intracisternal cocaine- and amphetamine-regulated transcript-derived peptides (CARTp)-induced inhibition of gastromotor function and acid secretion, respectively, are blocked by the Corticotropin-releasing factor (CRF) antagonist alpha-helical CRF 9-41 we previously investigated whether the hypophagic effect of CARTp elicited at a dorsal hindbrain level could be mediated
Post hoc analyses revealed a significant effect of 1 μg CARTp to reduce food intake at all the three time points

Summary

Introduction

Pre-treatment with the corticotropin-releasing factor antagonist α-helical CRF9-41 prevents inhibition of gastric emptying by cocaine-and amphetamine-regulated transcript peptide at a dorsal hindbrain level, but its inhibition of sucrose intake is not affected. This is suggestive of separable underlying mechanisms of action in the caudal brainstem for cocaine-and amphetamine-regulated transcript peptide with regard to food intake and gastrointestinal functions. We further examine cocaine-and amphetamine-regulated transcript peptide—corticotropin-releasing factor receptor interactions in caudal brainstem controls of solid food intake. We tested the hypothesis that cocaine- and amphetamine-regulated transcript-derived peptides (CARTp) can act at a caudal brainstem level to modify food intake via a CRF-receptor modulated mechanism. The dorsal hindbrain has a high density of CART-containing cells and nerves in multiple areas which are associated with controls for food intake

Methods

Results

Discussion

Conclusion