INVOLVEMENT OF NICOTINERGIC MECHANISMS IN THYROTROPIN-RELEASING HORMONE-INDUCED NEUROLOGIC RECOVERY AFTER CONCUSSIVE HEAD-INJURY IN THE MOUSE

A behavioral study was performed in an attempt to understand the neuro nal mechanisms involved in the thyrotropin-releasing hormone (TRH)-ind uced improvement of consciousness after concussive head injury in the mouse. Intravenous administration of TRH dose dependently shortened th e duration of unconsciousness after concussion in the mouse (ED50 = 3. 2 mg/kg). The improvement of recovery evoked by TRH (3 mg/kg i.v.) aft er concussion was not affected by i.p. pretreatment with N-(2-chloroet hyl)-N-ethyl-2-bromobenzylamine, alpha-methyl-para-tyrosine, p-chlorop henylalanine, scopolamine or methylscopolamine. However, mecamylamine or hexamethonium i.p. pretreatment completely inhibited the TRH-induce d improvement of outcome in traumatic brain injury. The results imply that TRH-induced improvement of recovery after concussion is not assoc iated with increased activity of monoaminergic neurons in the brain. T hese results suggest that the inhibitory effect of TRH upon unconsciou sness after concussion in mice is mainly produced by activation of cen tral cholinergic systems via nicotinic receptors whereas muscarinic re ceptors seem to be not implicated. (C) 1998 Elsevier Science B.V. All rights reserved.