Inactivation of a CRF-dependent amygdalofugal pathway reverses addiction-like behaviors in alcohol-dependent rats.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30886240.
- Also identified by DOI 10.1038/s41467-019-09183-0 and PMC identifier 6423296.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The activation of a neuronal ensemble in the central nucleus of the amygdala (CeA) during alcohol withdrawal has been hypothesized to induce high levels of alcohol drinking in dependent rats. In the present study we describe that the CeA neuronal ensemble that is activated by withdrawal from chronic alcohol exposure contains ~80% corticotropin-releasing factor (CRF) neurons and that the optogenetic inactivation of these CeA CRF+ neurons prevents recruitment of the neuronal ensemble, decreases the escalation of alcohol drinking, and decreases the intensity of somatic signs of withdrawal. Optogenetic dissection of the downstream neuronal pathways demonstrates that the reversal of addiction-like behaviors is observed after the inhibition of CeA CRF projections to the bed nucleus of the stria terminalis (BNST) and that inhibition of the CRF<sup>CeA-BNST</sup> pathway is mediated by inhibition of the CRF-CRF<sub>1</sub> system and inhibition of BNST cell firing. These results suggest that the CRF<sup>CeA-BNST</sup> pathway could be targeted for the treatment of excessive drinking in alcohol use disorder.
Medical subject headings
- Alcoholism
- Behavior, Addictive
- Central Amygdaloid Nucleus
- Corticotropin-Releasing Hormone
- Septal Nuclei