Neuroanatomically selective down-regulation of beta adrenergic receptors by chronic imipramine treatment: relationships to the topography of [3H]imipramine and [3H] desipramine binding sites.
The down-regulation of beta adrenergic receptors by chronic imipramine treatment was investigated with high resolution autoradiography of [125I]pindolol binding to brain sections. Neuroanatomically selective down-regulation of [125I]pindolol binding was found after chronic imipramine treatment. Subdivisions of the amygdala and hippocampus and discrete cortical regions were differentially affected. In the hippocampus, reduction of [125I]pindolol binding was observed in imipramine-treated rats in the CA-1 stratum radiatum and dentate molecular layer, but not in the CA-3 stratum radiatum. In the amygdala, the basolateral nucleus exhibited reduced [125I]pindolol binding after imipramine treatment but the central and medial nuclei were not affected. Chronic imipramine treatment was also associated with reduced [125I]pindolol binding in layer 1 of the cingulate cortex and layer 3 of the piriform cortex. In contrast, no effect on [125I]pindolol binding was apparent in the ventrolateral thalamic nucleus, caudate-putamen, lateral hypothalamus or layers 2 and 3 of the somatosensory cortex. In order to determine if regional variation in binding sites for imipramine, or its pharmacologically active metabolite desipramine, was responsible for the observed neuroanatomically selective reduction in [125I]pindolol binding, the binding of [3H]imipramine and [3H]desipramine was investigated. In some brain regions that exhibited high densities of [3H]imipramine and [3H]desipramine binding sites, [125I]pindolol binding was reduced after chronic treatment with imipramine. However, other regions that contained high densities of binding sites for antidepressant drugs did not show a reduction in [125I]pindolol binding after chronic imipramine treatment. Thus, regional binding of [3H]imipramine or [3H]desipramine cannot fully explain the neuroanatomical specificity of imipramine-induced beta adrenergic receptor down-regulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Duncan
G E
GE
Department of Cell Biology and Anatomy, School of Medicine, University of North Carolina, Chapel Hill.
Paul
I A
IA
Powell
K R
KR
Fassberg
J B
JB
Stumpf
W E
WE
Breese
G R
GR
D000818:Animals; D001345:Autoradiography; D001923:Brain Chemistry / Q000187:drug effects; D002352:Carrier Proteins; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D010869:Pindolol / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects*; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter / Q000032:analysis / Q000187:drug effects*
D002352:Carrier Proteins; D011943:Receptors, Adrenergic, beta; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter; C036079:desipramine receptor; C027775:imipramine receptor; D010869:Pindolol; D007099:Imipramine