A comparative study of effects of DOM and lisuride on neuronal activity in nucleus accumbens of freely moving rats.

Abstract

2,5-dimethoxy-4-methylamphetamine (DOM) and lisuride are both 5-HT2A receptor partial agonists. Lisuride exhibits a similar affinity to DOM but lacks hallucinogenic properties attributed to DOM. While extensive research has been conducted on their behavioral effects, a comparative analysis of their electrophysiological characteristics has not been documented. In this study, we employed multi-channel electrophysiological techniques to assess the effects of hallucinogen DOM and non-hallucinogen lisuride on neuronal activity in the Nucleus Accumbens (NAc) of freely moving rats. Our findings indicate that both DOM and lisuride increased the power of theta and High-Frequency Oscillations (HFO), reduced burst rates of putative medium spiny neurons (pMSNs), and enhanced correlations between pMSNs spiking and theta band activity. Additionally, DOM decreased low gamma power, whereas lisuride increased it. Furthermore, DOM decreased the spiking rate of putative fast-spiking interneurons (pFSIs) while lisuride increased it. DOM also reduced burst rates of pFSIs, whereas lisuride had no effect. Notably, DOM induced increased synchronous discharges between pFSIs and low gamma rhythm, a phenomenon not observed with lisuride. The consistent effects of both drugs on theta and HFO power, pMSNs firing patterns, and correlations between pMSNs spiking and theta rhythm suggest common mechanisms underlying their actions. Conversely, differences in low gamma power, pFSIs firing patterns, and correlations between pFSIs spiking and low gamma rhythm serve as key distinguishing factors. These differences in electrophysiological responses might contribute to the distinct behavioral effects associated with hallucinogenic and non-hallucinogenic properties of these compounds. The results will provide electrophysiological evidence for treatment of related psychotomimetic symptoms.