Modulation of aggressive behavior in mice by nicotinic receptor subtypes

摘要: Aggression is frequently comorbid with neuropsychiatric conditions and a predictor of worse outcomes, yet current pharmacotherapies are insufficient have debilitating side effects, precluding broad use. Multiple models aggression across species suggest that the nicotinic acetylcholine receptor (nAChR) agonist nicotine has anti-aggressive (serenic) properties. Here we demonstrate dose-dependent serenic effects acute administration in three distinct mouse strains: C57BL/6, BALB/c, CD1. While (0.25 mg/kg) modestly reduced solitary homecage locomotion, this could not account for nicotine’s since social encounters eliminated hypolocomotor effect, did alter interaction times. Pretreatment homomeric (α7 subunit) nAChR antagonist methyllycaconitine (5 mg/kg), but heteromeric (β2 or β4 subunit-containing) dihydro-β-erythroidine (DHβE, 3 blocked nicotine. By contrast, pretreatment DHβE effect on uncoupling effects. Finally, α7 partial GTS-21 C57BL/6 mice. These results support idea provide evidence specificity from locomotion. Furthermore, pharmacological studies activation nAChRs underlies Further enhance understanding neurobiology may lead to development novel, more specific treatments pathological aggression.