title: Neuroanatomical differences in the rate of beta-adrenergic receptor adaptation after repeated treatment with imipramine.
abstract: 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.
authors.affiliation: Brain and Development Research Center, University of North Carolina, Chapel Hill 27699.
authors.forename: G E
authors.initials: GE
authors.lastname: Duncan
authors.forename: I A
authors.initials: IA
authors.lastname: Paul
authors.forename: G R
authors.initials: GR
authors.lastname: Breese
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
chemical_list: D011943:Receptors, Adrenergic, beta; D007099:Imipramine