Effects of thyrotropin-releasing hormone on phencyclidine- and ketamine-induced spinal depression in neonatal rats.
The effects of thyrotropin-releasing hormone (TRH) were examined on the monosynaptic reflex and on the activity of motoneurons in the spinal cord of the neonatal rat to elucidate the mechanism of action of TRH and its ability to reverse the spinal depression caused by phencyclidine and ketamine. Phencyclidine (2-32 microM) and ketamine (25-200 microM) produced a concentration-dependent depression of the monosynaptic reflex with a 50% inhibitory concentration (IC50) of 8.4 and 77.5 microM, respectively. This depression, however, was significantly attenuated by simultaneous application of TRH (0.03-1 microM) in a concentration-dependent manner. The dose-response curves for phencylidine and ketamine were shifted to the right in the presence of TRH (0.1 microM) with an increase in the respective IC50 of 2- to 3-fold. The incidence of generation of motoneuron spikes, elicited by dorsal root stimulation, was significantly increased by TRH in each neuron tested, concomitantly with an increase in the spontaneous firing rate. These results suggest that TRH directly excites alpha-motoneurons to reverse the spinal depression produced by phencylidine and ketamine.
Ohno
Y
Y
Department of Pharmacology and Experimental Therapeutics, University of Maryland, School of Medicine, Baltimore 21201.
Warnick
J E
JE
D000818:Animals; D000831:Animals, Newborn; D007649:Ketamine / Q000633:toxicity*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects; D010622:Phencyclidine / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012023:Reflex, Monosynaptic / Q000187:drug effects; D013127:Spinal Nerves / Q000187:drug effects*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
D013973:Thyrotropin-Releasing Hormone; D007649:Ketamine; D010622:Phencyclidine