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 neuronal mechanisms involved in the thyrotropin-releasing hormone (TRH)-induced improvement of consciousness after concussive head injury in the mouse. Intravenous administration of TRH dose dependently shortened the 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.) after concussion was not affected by i.p. pretreatment with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, alpha-methyl-para-tyrosine, p-chlorophenylalanine, scopolamine or methylscopolamine. However, mecamylamine or hexamethonium i.p. pretreatment completely inhibited the TRH-induced improvement of outcome in traumatic brain injury. The results imply that TRH-induced improvement of recovery after concussion is not associated with increased activity of monoaminergic neurons in the brain. These results suggest that the inhibitory effect of TRH upon unconsciousness after concussion in mice is mainly produced by activation of central cholinergic systems via nicotinic receptors whereas muscarinic receptors seem to be not implicated.
Lestage
P
P
Division of Cerebral Pathology, Institut de Recherches SERVIER, Croissy-sur-Seine, France.
Iris-Hugot
A
A
Gandon
M H
MH
Lepagnol
J
J
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001924:Brain Concussion / Q000188:drug therapy*; D018680:Cholinergic Antagonists / Q000494:pharmacology; D003243:Consciousness / Q000187:drug effects*; D008297:Male; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000502:physiology*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*; D013997:Time Factors
D015306:Biogenic Monoamines; D018680:Cholinergic Antagonists; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D013973:Thyrotropin-Releasing Hormone