The roles of 5-HT1A and 5-HT2 receptors in the effects of 5-MeO-DMT on locomotor activity and prepulse inhibition in rats

Rationale The hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is structurally similar to other indoleamine hallucinogens such as LSD. The present study examined the effects of 5-MeO-DMT in rats using the Behavioral Pattern Monitor (BPM), which enables analyses of patterns of locomotor activity and exploration, and the prepulse inhibition of startle (PPI) paradigm. Objectives A series of interaction studies using the serotonin (5-HT)(1A) antagonist WAY-100635 (1.0 mg/kg), the 5-HT2A antagonist M100907 (1.0 mg/kg), and the 5-HT2C antagonist SER-082 (0.5 mg/kg) were performed to assess the respective contributions of these receptors to the behavioral effects of 5-MeO-DMT (0.01, 0.1, and 1.0 mg/kg) in the BPM and PPI paradigms. Results 5-MeO-DMT decreased locomotor activity, investigatory behavior, the time spent in the center of the BPM chamber, and disrupted PPI. All of these effects were antagonized by WAY-100635 pretreatment. M100907 pretreatment failed to attenuate any of these effects, while SER-082 pretreatment only antagonized the PPI disruption produced by 5-MeO-DMT. Conclusions While the prevailing view was that the activation of 5-HT2 receptors is solely responsible for hallucinogenic drug effects, these results support a role for 5-HT1A receptors in the effects of the indoleamine hallucinogen 5-MeO-DMT on locomotor activity and PPI in rats.