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

Two types of hallucinogens that affect serotonin systems have both shared and distinct effects on spinal reflexes in rats. 5-MeODMT (an indolealkylamine) decreased the monosynaptic reflex in a dose-dependent way, while DOI (a phenylalkylamine) increased it. Both drugs increased the polysynaptic reflex. Antagonists blocking 5-HT2 receptors prevented DOI's effects on the monosynaptic reflex but only partially blocked those of 5-MeODMT. The same antagonists inhibited DOI-induced changes in the polysynaptic reflex but not those caused by 5-MeODMT. Neither propranolol nor MDL 72222 blocked either drug's effects. Both hallucinogens increased motoneuron excitability via 5-HT2 receptors, but only 5-MeODMT inhibited the monosynaptic reflex pathway.

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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 micrograms/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 micrograms/kg), a phenylalkylamine agent, produced a dose-dependent increase in the monosynaptic reflex. Both agents increased the polysynaptic reflex. The 5-HT2 receptor antagonists ketanserin (100 micrograms/kg) and ritanserin (100 micrograms/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-HT2 receptors but (2) only 5-MeODMT has an inhibitory action on the pathway of the monosynaptic reflex.