| Description |
Brief repetitive stimulation of excitatory pathways in the cervical dorsolateral funiculus of unanesthetized, spinal cats produced long-term potentiation (LTP) of subsequent intraspinally evoked (0.1 Hz) discharges recorded from upper thoracic pregangllionic rami. Amplitude and duration of LTP were dependent on frequency (25-75 Hz) and duration (5-20 sec) of titanic stimulation. Following stimulation at 50Hz for 10 sec, posttetanic discharges reached maximal sizes of 120-600% of pretatanic control values within 90 sec and thereafter slowly declined to control values of higher levels by about 20 minutes. Repeated tetanizations of 20 min. intervals produce incremental increases in steady transmission which correlated directly with amplitude of LTP. Aminophylline (50 mg/kg), a phosphodiesterase inhibitor, markedly enhanced intraspinal transmission of 0.1Hz but did not enhance subsequent LTPs. Similarly, tolazoline HCI (25mg/kg), an alpha-2 receptor antagonist, enhanced intraspinal transmission at 0.1 Hz but did not enhance the development of subsequent LTPs. Clonidine HCI (20 ug/kg), D,L,5HTP (40 mg/kg) and morphine SO4 (1.0mg/kg), selective depressants of sympathetic preganglionic neurons, depressed intraspinal transmission at 0.1 Hz, but did not prevent the development of LTP. In contrast, chlorpromazine (4.5 mg/kg), an antipsychotic drug that appears to block central norepinephrine (NE) receptors, almost completely prevented the development of LTP. Lidocaine HCI (14 mg/kg), a local anesthetic which depresses presynaptic release of neurotransmitter, depressed intraspinal transmission at 0.1 Hz and depressed the development of LTP. The results indicate that LTP has a longer onset and duration that posttetanic potentiation in spinal monosynaptic reflex pathways. The mechanism of LTP does not appear to involve the postsynaptic accumulation of cyclic AMP or to changes in postsynaptic excitability. Rather, LTP appears to be due to enhance release of neurotransmitter, possible norepinephrine. Clinically, LTP and the incremental increases in baseline transmission produced by intermittent, intense activation of descending pathways may contribute to the development of some forms of essential hypertension. The results also suggest that orthostatic and exercise hypotension commonly produce by chlorpromazine but not by cloidine may reflect the differences in their effects on LTP in descending sympathetic pathways. |
