Journal
ADDICTION BIOLOGY
Volume 17, Issue 5, Pages 908-919Publisher
WILEY
DOI: 10.1111/j.1369-1600.2011.00392.x
Keywords
Addiction; dopamine; food intake; ghrelin; phMRI; reward
Categories
Funding
- NIH [R01-013188]
Ask authors/readers for more resources
Ghrelin (GHR) is an orexigenic gut peptide that interacts with brain ghrelin receptors (GHR-Rs) to promote food intake. Recent research suggests that GHR acts as a modulator of motivated behavior, suggesting a direct influence of GHR on brain reinforcement circuits. In the present studies, we investigated the role of GHR and GHR-Rs in brain reinforcement function. Pharmacological magnetic resonance imaging was used to spatially resolve the functional activation produced by systemic administration of an orexigenic GHR dose. The imaging data revealed a focal activation of a network of subcortical structures that comprise brain reinforcement circuitsventral tegmental area, lateral hypothalamus and nucleus accumbens. We next analyzed whether brain reinforcement circuits require functional GHR-Rs. To this purpose, wild-type (WT) or mutant rats sustaining N-ethyl-N-nitrosourea-induced knockout of GHR-Rs (GHR-R null rats) were implanted with stimulating electrodes aimed at the lateral hypothalamus, shaped to respond for intracranial self-stimulation (ICSS) and then tested using a rate-frequency procedure to examine ICSS response patterns. WT rats were readily shaped using stimulation intensities of 75 mu A, whereas GHR-R null rats required 300 mu A for ICSS shaping. No differences in rate-frequency curves were noted for WT rats at 75 mu A and GHR-R null rats at 300 mu A. When current intensity was lowered to 100 mu A, GHR-R null rats did not respond for ICSS. Taken collectively, these data suggest that systemic GHR can activate mesolimbic dopaminergic areas, and highlight a facilitative role of GHR-Rs on the activity of brain reinforcement systems.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available