Desmethylimipramine-induced decrease in β-adrenergic receptor binding in rat cerebral cortex

Effect of destruction of central noradrenergic and serotonergic nerve terminals by systemic neurotoxins on the long-term effects of antidepressants on?-adrenoceptors and 5-HT2 binding sites in the rat cerebral cortex

“…Several of these antidepressants also produce a simultaneous reduction of the density of the fl-adrenoceptors when measured with ligand techniques (Banerjee et aL, 1977;Wolfe et aL, 1978;Sarai et aL, 1978). Mishra et al (1980) found that long-term treatment of rats with mianserin or zimeldine only reduced the noradrenaline stimulated adenylate cyclase activity without decreasing the density of the //-adrenoceptors.…”

Acute and chronic effects of antidepressant drugs on β‐adrenergic function in astrocytes in primary cultures: An indication of glial involvement in affective disorders?

“…Over the last few years, studies initiated by Sulser and coworkers have demonstrated that the administration over several weeks of any antidepressant drug causes a downregulation of cerebral adrenergic receptor function in the rat brain. This downregulation, which is not seen after drug treatment for only a few days, is reflected by decreases in P-receptor binding and in adenylyl cyclase stimulation by isoproterenol , a 0-adrenergic agonist [Vetulani and Sulser, 1975;Vetulani et al, 1976;Schultz, 1976;Banerjee et a], 1977;Sulser, 1978Sulser, , 1979Wolfe et al, 1978;Frazer et al, 1978;Sarai et al, 1978;Clements-Jewery, 1978;Sellinger-Barnette et al, 1980;Kinnier et al, 1980;Mishra et al, 1980;Asakura et al, 19823. Although no information is available about the exact mechanism@) of this down-regulation, it is known that dihydroalpren-0101, a 0-adrenergic ligand, can be displaced from brain membranes by at least some tricyclic antidepressants, although less potently than by classical 0-adrenergic agonists or antagonists [Bylund and Snyder, 1976;Wolfe et al, 1978;Hall and Ogren, 19811.…”

Modulation of neuronal serotonin uptake by a putative endogenous ligand of imipramine recognition sites.

“…Their capacity to block norepinephrine (NE) and serotonin (5-hydroxytryptamine; 5HT) uptake has been considered to be important for their therapeutic action, but when it was noted that imipramine and DMI block amine uptake almost instantaneously, whereas their antidepressant action occurs with a latency time of 1-2 weeks (1), the importance of the uptake inhibition in explaining their therapeutic action was deemphasized. Upon repeated daily administration to rats imipramine and a number of its congeners down-regulate the function of NE recognition sites in several brain structures (3)(4)(5)(6); because the onset of this down-regulation and that of the antidepressant action are delayed with respect to the beginning of the treatment, it has been suggested that the NE response downregulation and the antidepressant action may be related (6). An additional tool to study the mechanism of the down-regulation of /3-adrenergic receptors became available when Langer and his colleagues reported that specific Na+-dependent and highaffinity binding sites for [3H]imipramine are located in crude synaptic membranes prepared from various structures of mammalian brains (7,8).…”