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 adaptation that occurs during chronic imipramine treatment varies among specific 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 analysis of [125I]-pindolol binding after different periods of imipramine treatment. The duration of imipramine treatment required to down-regulate the receptors varied markedly among different brain regions. Select cortical regions exhibited a reduction in [125I]-pindolol binding after only two injections of imipramine. These rapidly adapting cortical 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 was observed. Such slowly adapting regions included subdivisions of the hypothalamus and amygdala. Other brain regions examined required intermediate periods of imipramine treatment, of 4 to 14 days, to produce a reduction in beta-adrenergic binding. It is possible that differential rates of neural adaptation among brain regions are related to the time course of therapeutic response to antidepressant drug treatment.