Desensitization by Antidepressants of Central Norepinephrine Receptor Systems Coupled to Adenylate Cyclase^a

Neutrophil β 2 -adrenergic receptor coupling efficiency to Gs protein in subjects with post-traumatic stress disorder and normal controls

“…Increased AR density and supercoupling in PTSD may be consistent with reported mechanisms of action of antidepressants, which downregulate AR density, particularly in the high-conformational state, induce AR uncoupling and decrease cAMP responses (Banerjee et al 1977;Sulser 1979;Sulser et al 1984;Charney et al 1981;Hancock and Marsh 1985;Okada et al 1986;Manier et al 1987;Tsuchiya et al 1988). The present findings may underlie the partial efficacy of antidepressants, particularly tricyclics and monoamine oxidase inhibitors, in the treatment of PTSD, which have been shown to improve not only anxiety and depressive symptoms, but also PTSD-specific symptomatology (for review, see Southwick et al 1994).…”

Gαs, adenylyl cyclase, and their relationship to the diagnosis and treatment of depression

“…Antidepressant treatment also causes a shift in the localization of the heterotrimeric G protein, Gα s , from lipid rafts to more "fluid" membrane regions, facilitating Gα s activation of adenylyl cyclase (AC). Both diminished Gα s -adenylyl cyclase coupling and an increase in the proportion of Gα s in lipid rafts are seen in depression (postmortem and peripheral tissue) (Donati et al, 2008;Singh et al, 2020;Targum et al, 2022), and this is consistent with the augmentation of cAMP production by antidepressants. There are also compounds, such as ketamine, and, perhaps psychedelics, that appear to exert more rapid effects on depression, acting in hours rather than weeks for traditional antidepressants.…”

Gender difference in the prevention of hyperanxiety in adult prenatally stressed rats by chronic treatment with amitriptyline

“…An increase in anxiety, together with a depression of exploratory behaviour, has been reported for other TCAs after both acute and chronic administration of different doses of the drugs and was seen in both control male rats and those stressed acutely as adults (Van Dijken et al 1992;Silva et al 1999;Borsini et al 2002). The anxiogenic effect of TCAs could result from down-regulation of pre-and postsynaptic aminergic receptors and post-receptor signalling, consequent to continuous inhibition of amine re-uptake (Sulser et al 1984;Paul et al 1988), in animals with normal aminergic transmission. It is possible that in PS rats, which have a higher noradrenaline turnover than controls (Takahashi et al 1992), chronic antidepressant treatment may reduce excess amine release as it did in rats that had been subjected to recurring stress (Dazzi et al 2002), thereby causing less down-regulation of aminergic receptors than in C rats.…”