Lesions of the serotonergic system impair the facilitation of but not the tolerance to the effects of chronic clenbuterol administration.
Acute clenbuterol, a beta-adrenergic stimulant, decreases motility and antagonizes reserpine-induced hypothermia in mice. After repeated treatment with clenbuterol, the hypomotility disappears (tolerance) but the antagonism of reserpine-induced hypothermia increases (facilitation). To investigate the function of serotonin in tolerance and facilitation, lesions of the serotonergic system were performed by intracerebroventricular administration of the neurotoxin 5,7 dihydroxytryptamine (5,7-DHT). After lesions of the serotonergic system, the tolerance to clenbuterol-induced hypomotility persists, but the facilitation of the antagonism by clenbuterol of reserpine-induced hypothermia disappears. Thus, the serotonergic nerve terminals must be intact for the latter but not the former response to occur. Since the reversal of reserpine-induced hypothermia in animals is predictive of antidepressant effects in man, it is suggested that the therapeutic action of clenbuterol in depressed patients may be mediated through the serotonergic system.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002976:Clenbuterol / Q000494:pharmacology*; D004361:Drug Tolerance; D004983:Ethanolamines / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*
D004983:Ethanolamines; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D012110:Reserpine; D002976:Clenbuterol