NEUROANATOMICAL DIFFERENCES IN THE RATE OF BETA-ADRENERGIC-RECEPTOR ADAPTATION AFTER REPEATED TREATMENT WITH IMIPRAMINE

We tested the hypothesis that the time course of neurochemical adaptat ion that occurs during chronic imipramine treatment varies among speci fic brain regions. Down-regulation of brain beta-adrenergic receptors was used as a model of antidepressant-induced neural adaptation. Beta- adrenergic receptors were assessed by quantitative autoradiographic an alysis of [I-125]-pindolol binding after different periods of imiprami ne treatment. The duration of imipramine treatment required to downreg ulate the receptors varied markedly among different brain regions. Sel ect cortical regions exhibited a reduction in [I-125]-pindolol binding after only two injections of imipramine. These rapidly adapting corti cal regions included the medial prefrontal, ventrolateral orbital, and piriform cortices. In contrast, some brain regions required a 3-week treatment period before down-regulation of beta-adrenergic receptors w as observed. Such slowly adapting regions included subdivisions of the hypothalamus and amygdala. Other brain regions examined required inte rmediate periods of imipramine treatment, of 4 to 14 days, to produce a reduction in beta-adrenergic binding. It is possible that differenti al rates of neural adaptation among brain regions are related to the t ime course of therapeutic response to antidepressant drug treatment.