Citation

Quadros IM, Hwa LS, Shimamoto A, Carlson J, Debold JF, Miczek KA. Neuropsychopharmacology 2014; 39(12): 2874-2883.

Affiliation

Department of Psychology, Tufts University, Medford, MA, Departments of Neuroscience, Psychiatry, Pharmacology, Tufts University, Boston, MA.

Copyright

(Copyright © 2014, Nature Publishing Group)

DOI

10.1038/npp.2014.139

PMID

24917195

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 raphé 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, while systemic administration reduced both alcohol-heightened and species-typical aggression. Next, a 5-HT1A agonist, 8-OH-DPAT, was co-administered with CP-154,526 into the DRN to temporarily disrupt 5-HT activity. This manipulation abolished the anti-aggressive 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 then were 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.Neuropsychopharmacology accepted article preview online, 11 June 2014; doi:10.1038/npp.2014.139.

Language: en