title: Escalated aggression after alcohol drinking in male mice: dorsal raphé and prefrontal cortex serotonin and 5-HT(1B) receptors.
abstract: A significant minority of individuals engages in escalated levels of aggression after consuming moderate doses of alcohol (Alc). Neural modulation of escalated aggression involves altered levels of serotonin (5-HT) and the activity of 5-HT(1B) receptors. The aim of these studies was to determine whether 5-HT(1B) receptors in the dorsal raphé (DRN), orbitofrontal (OFC), and medial prefrontal (mPFC) cortex attenuate heightened aggression and regulate extracellular levels of 5-HT. Male mice were trained to self-administer Alc by performing an operant response that was reinforced with a delivery of 6% Alc. To identify Alc-heightened aggressors, each mouse was repeatedly tested for aggression after consuming either 1.0 g/kg Alc or H2O. Next, a cannula was implanted into either the DRN, OFC, or mPFC, and subsets of mice were tested for aggression after drinking either Alc or H(2)O prior to a microinjection of the 5-HT(1B) agonist, CP-94,253. Additional mice were implanted with a microdialysis probe into the mPFC, through which CP-94,253 was perfused and samples were collected for 5-HT measurement. Approximately 60% of the mice were more aggressive after drinking Alc, confirming the aggression-heightening effects of 1.0 g/kg Alc. Infusion of 1 microg CP-94,253 into the DRN reduced both aggressive and motor behaviors. However, infusion of 1 microg CP-94,253 into the mPFC, but not the OFC, after Alc drinking, increased aggressive behavior. In the mPFC, reverse microdialysis of CP-94,253 increased extracellular levels of 5-HT; levels decreased immediately after the perfusion. This 5-HT increase was attenuated in self-administering mice. These results suggest that 5-HT(1B) receptors in the mPFC may serve to selectively disinhibit aggressive behavior in mice with a history of Alc self-administration.
authors.affiliation: Department of Psychology, Tufts University, Medford, MA, USA. sara_faccidomo@med.unc.edu
authors.forename: Sara
authors.initials: S
authors.lastname: Faccidomo
authors.forename: Makoto
authors.initials: M
authors.lastname: Bannai
authors.forename: Klaus A
authors.initials: KA
authors.lastname: Miczek
mesh_terms: D000374:Aggression / Q000187:drug effects* / Q000502:physiology; D020268:Alcohol-Induced Disorders, Nervous System / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology*; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008845:Microinjections; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D011903:Raphe Nuclei / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects* / Q000378:metabolism; D012054:Reinforcement, Psychology; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D002492:Central Nervous System Depressants; D044302:Receptor, Serotonin, 5-HT1B; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D000431:Ethanol