TIME COURSE OF CHANGES IN SENSITIVITY AFTER DENERVATION OF THE NICTITATING MEMBRANE OF THE SPINAL CAT

¹ Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

Dose-response curves for norepinephrine and tyramine were determined in spinal cats at various time intervals after denervation and decentralization of the nictitating membrane. Changes in sensitivity were determined by measuring horizontal distances between dose-response curves.

In confirmation of earlier work, supersensitivity to norepinephrine after decentralization was found to develop gradually during the whole period of 14 days after the operation. The magnitude of supersensitivity to tyramine was equal to that to norepinephrine at any time after decentralization.

On the first postoperative day there was no difference in sensitivity to norepinephrine between the denervated and the decentralized side. On the second day the denervated side had more than 10 times the sensitivity to norepinephrine of the decentralized side, and this difference did not increase significantly beyond the second day. With tyramine, on the other hand, a slight increase in sensitivity of the denervated over the decentralized nictitating membrane occurred on the first postoperative day, whereas a considerable decrease in sensitivity was found on the second and fourth days. At this time the maximal response to tyramine was also reduced.

The results suggest that denervation super-sensitivity to norepinephrine consists of two components with different time course of development. Whereas the decentralization-like component requires 14 days for full development, the cocaine-like component requires not more than 24 hours between the first and second postoperative day. The experiments with tyramine and reports in the literature suggest that the development of the latter component coincides with degeneration of nerve terminals and loss of their function.