Presynaptic alpha-receptor subsensitivity after long-term antidepressant treatment

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Science  20 Oct 1978:
Vol. 202, Issue 4365, pp. 322-324
DOI: 10.1126/science.211589


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.