Stimulatory and inhibitory effects of serotonergic hallucinogens on spinal mono-and polysynaptic reflex pathways in the rat

Abstract

The effects of two 5-HT-related hallucinogens on rat spinal mono- and polysynaptic reflex pathways in the rat were investigated. 5-Methoxy- N, N,-dimethyltryptamine (5-MeODMT, 1 and 100 μg/kg, i.V.), an indolealkylamine agent, produced a dose-dependent decrease in the monosynaptic reflex, whereas 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane(DOI, 1–100 μg/kg), a phenylalkylamine agent, produced a dose-dependent increase in the monosynaptic reflex. Both agents increased the polysynaptic reflex. The 5-HT 2 receptor antagonists ketanserin (100 μg/kg) and ritanserin (100 μg/kg) blocked the effects of DOI on the monosynaptic reflex but only partially blocked the 5-MeODMT-induced effect on the monosynaptic reflex. These antagonists inhibited the change in polysynaptic reflex, induced by DOI but not by 5-MeODMT. Neither propranolol (1 mg/kg) nor 3-tropanyl-3,5-dichlorobenzoate (MDL 72222, 1 mg/kg) antagonized the effect of either agent. 5-Methoxy- N, N-dimethyltryptamine and DOI increased the excitability of motoneurons and this effect was inhibited by ketanserin. These results indicate that the two types of hallucinogens possess both common and distinct characteristics, with regard to their action on the spinal reflex: (1) both increase the activity of motoneurons through 5-HT 2 receptors but (2) only 5-MeODMT has an inhibitory action on the pathway of the monosynaptic reflex.