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Science 20 October 1978:
Vol. 202. no. 4365, pp. 322 - 324
DOI: 10.1126/science.211589
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Articles

Science, Vol 202, Issue 4365, 322-324
Copyright © 1978 by American Association for the Advancement of Science

articles

Presynaptic alpha-receptor subsensitivity after long-term antidepressant treatment

FT Crews and CB Smith

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.


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