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Prevention of alcohol-heightened aggression by CRF-R1 antagonists in mice: critical role for DRN-PFC serotonin pathway.
- 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.
- Subjects :
- 8-Hydroxy-2-(di-n-propylamino)tetralin pharmacology
Aggression physiology
Alcohol Drinking physiopathology
Alcohol Drinking psychology
Animals
Central Nervous System Agents pharmacology
Dorsal Raphe Nucleus drug effects
Dorsal Raphe Nucleus physiology
Mice
Neural Pathways drug effects
Neural Pathways physiology
Prefrontal Cortex drug effects
Prefrontal Cortex physiology
Pyridazines pharmacology
Pyrimidines pharmacology
Pyrroles pharmacology
Receptor, Serotonin, 5-HT1A metabolism
Receptors, Corticotropin-Releasing Hormone metabolism
Self Administration
Serotonin metabolism
Serotonin 5-HT1 Receptor Agonists pharmacology
Thiazoles pharmacology
Aggression drug effects
Central Nervous System Depressants administration & dosage
Ethanol administration & dosage
Receptors, Corticotropin-Releasing Hormone antagonists & inhibitors
Subjects
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