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.