Back to Search Start Over

Prevention of alcohol-heightened aggression by CRF-R1 antagonists in mice: critical role for DRN-PFC serotonin pathway.

Authors :
Quadros IM
Hwa LS
Shimamoto A
Carlson J
DeBold JF
Miczek KA
Source :
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2014 Nov; Vol. 39 (12), pp. 2874-83. Date of Electronic Publication: 2014 Jun 11.
Publication Year :
2014

Abstract

Alcohol can escalate aggressive behavior in a significant subgroup of rodents, humans, and nonhuman primates. The present study investigated whether blockade of corticotropin-releasing factor receptor type 1 (CRF-R1) could prevent the emergence of alcohol-heightened aggression in mice. The serotonin (5-HT) pathway from the dorsal raphe nucleus (DRN) to the medial prefrontal cortex (mPFC) by CRF-R1 was investigated as a possible target for the prevention of alcohol-heightened aggressive behavior. Male CFW mice that reliably exhibited aggressive behaviors after consuming 1 g/kg of alcohol received systemic or intra-DRN administration of CRF-R1 antagonists, CP-154,526 or MTIP, before a confrontation with a male conspecific. Blockade of DRN CRF-R1 receptors with both antagonists significantly reduced only alcohol-heightened aggression, whereas systemic administration reduced both alcohol-heightened and species-typical aggression. Next, a 5-HT1A agonist, 8-OH-DPAT, was coadministered with CP-154,526 into the DRN to temporarily disrupt 5-HT activity. This manipulation abolished the antiaggressive effects of intra-DRN CP-154,526. In the mPFC, in vivo microdialysis revealed that extracellular 5-HT levels were increased in mice that consumed alcohol and were then injected with CP-154,526, both systemically or intra-DRN. Neither alcohol nor CP-154,526 alone affected 5-HT release in the mPFC. The present results suggest the DRN as a critical site for CRF-R1 to modulate alcohol-heightened aggression via action on the serotonergic DRN-PFC pathway.

Details

Language :
English
ISSN :
1740-634X
Volume :
39
Issue :
12
Database :
MEDLINE
Journal :
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Publication Type :
Academic Journal
Accession number :
24917195
Full Text :
https://doi.org/10.1038/npp.2014.139