Noradrenergic and serotonergic input necessary for imipramine-induced changes in beta but not S2 receptor densities.
Chronic imipramine administration decreases the density of serotonin S2 and beta-adrenergic receptors. The mode of action is not clear but might be assumed to be a result of imipramine interacting with its high affinity binding sites on presynaptic serotonin neurons. To investigate this possibility and the role of the serotonergic and noradrenergic systems on imipramine-induced receptor down-regulations, the effects of raphe lesions and 6-hydroxydopamine lesions were examined. The theory that imipramine acts through the serotonin system to down-regulate beta-adrenergic receptors was supported by the observation that raphe lesions attenuated the imipramine-induced beta receptor denumeration. However, the effect of imipramine on the S2 site may not be a result of serotonin uptake blockade. Raphe lesions which diminish 3H-imipramine high affinity binding did not alter the imipramine-induced decrease in S2 receptor numbers. 6-Hydroxydopamine lesions prevented the reduction in beta but not S2 binding. Imipramine may exert its effect on S2 binding through a site other than the high affinity, serotonin uptake site.
D000818:Animals; D004082:Dihydroalprenolol; D006892:Hydroxydopamines / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine; D011903:Raphe Nuclei / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D013134:Spiperone; D014316:Tritium
D006892:Hydroxydopamines; D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin; D014316:Tritium; D012701:Serotonin; D013134:Spiperone; D004082:Dihydroalprenolol; D016627:Oxidopamine; D007099:Imipramine; D009638:Norepinephrine