Presynaptic alpha-receptor subsensitivity after long-term antidepressant treatment.
After 3 weeks of twice-daily administration of desipramine to rats, the frequency-response curve for field stimulation of adrenergic neurons in isolated left atrial strips was shifted markedly to the left and the efflux of [3H]norepinephrine was enhanced greatly. After 1 day of treatment, only slight shifts in the frequency-response curve and small increases in [3H]norepinephrine efflux occurred although inhibition of [3H]norepinephrine uptake was already maximal, and phenoxybenzamine caused a further shift to the left in the frequency-response curve similar to that which occurred after 3 weeks of desipramine treatment alone. A gradual decrease in the sensitivity of the presynaptic alpha receptor would explain the delay in the onset of the linical effect of the tricyclic antidepressants.
D000818:Animals; D003891:Desipramine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D009469:Neuromuscular Junction / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D013570:Synaptic Membranes / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D010643:Phenoxybenzamine; D003891:Desipramine; D009638:Norepinephrine