Neuroanatomical specificity and dose dependence in the time course of imipramine-induced beta adrenergic receptor down-regulation in rat brain.
The time course of beta adrenergic receptor adaptation in response to chronic imipramine treatment (10 or 20 mg/kg) was assessed by quantitative autoradiographic analysis of 125I-pindolol binding in rat brain. Binding of the radioligand was assessed in 18 brain areas, including subregions of the hippocampus, amygdala, septum, hypothalamus and specific cerebral cortical regions. After only 2 days treatment with imipramine at a dose of 20 mg/kg, select cortical regions exhibited a reduction in 125I-pindolol binding. These rapidly adapting cortical regions included the medial prefrontal, lateral frontal, ventrolateral orbital and piriform cortices. After 7 or 21 days treatment with imipramine at 20 mg/kg, 16 of 18 brain regions examined exhibited significant reduction in 125I-pindolol binding. The only regions examined that did not show reduced 125I-pindolol binding for these treatment conditions were the caudate-putamen and anterior hypothalamic area. After 2 days treatment with 10 mg/kg of imipramine, down-regulation of beta adrenergic receptors was not observed in any region. After 7 days treatment with 10 mg/kg, down-regulation of beta adrenergic receptor binding was found only in certain cortical regions: medial prefrontal, lateral frontal, ventrolateral orbital and piriform cortices. Thus, the cortical regions that were most rapidly affected with the 20 mg/kg dose of imipramine (i.e., after 2 days) were also the first to respond with the 10 mg/kg dose of the drug. After 21 days treatment with imipramine at 10 mg/kg, 125I-pindolol binding was reduced in 13 of the 18 regions examined.(ABSTRACT TRUNCATED AT 250 WORDS)
Duncan
G E
GE
Brain and Development Research Center, University of North Carolina at Chapel Hill.
Knapp
D J
DJ
Little
K Y
KY
Breese
G R
GR
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; C029247:3-iodopindolol; D010869:Pindolol; D007099:Imipramine