The roles of 5-HT1A and 5-HT2 receptors in the effects of 5-MeO-DMT on locomotor activity and prepulse inhibition in rats
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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.
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.
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.
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.
KeywordsHallucinogen 5-MeO-DMT M100907 SER-082 WAY-100635 Rat Locomotion Startle Prepulse inhibition PPI
- Dumuis A, Sebben M, Bockaert J (1987) Pharmacology of 5-hydroxytryptamine-1A receptors which inhibit cAMP production in hippocampal and cortical neurons in primary culture. Mol Pharmacol 33:178–186Google Scholar
- Geyer MA (1990) Approaches to the characterization of drug effects on locomotor activity in rodents. In: Adler MW, Cowan A (eds) Modern methods in pharmacology: testing and evaluation of drugs of abuse. Wiley, New York, pp 81–99Google Scholar
- Geyer MA, Krebs KM (1994) Serotonin receptor involvement in an animal model of the acute effects of hallucinogens. In: Lin G, Glennon RA (eds) Hallucinogens: an update (NIDA Research Monograph Series). US Department of Health and Human Services, Rockville, MD, pp 124–156Google Scholar
- Holmstedt B, Lindgren JE, Plowman T, Rivier L, Schultes RE, Tovar O (1980) Indole alkaloids in Amazonian Myristicaceae: field and laboratory research. Bot Mus Leaf Harv Univ 28:215–234Google Scholar
- Krebs-Thomson K, Geyer MA (1996) The role of 5-HT1A receptors in the locomotor-suppressant effects of LSD: WAY-100635 studies of 8-OH-DPAT, DOI, and LSD. Behav Pharmacol 6:551–559Google Scholar
- Schultes RE, Raffauf RF (1995) The healing forest: medicinal and toxic plants of the northwest Amazonia. Dioscorides, PortlandGoogle Scholar
- Shulgin A, Shulgin A (1997) TiHKAL: the continuation. Transform, Berkeley, CAGoogle Scholar
- Spencer DG, Glaser T, Traber J (1987) Serotonin receptor subtype mediation of the interoceptive discriminative stimuli induced by 5-methoxy-N,N-dimethyltryptamine. Psychopharmacology (Berl) 93:158–166Google Scholar
- Thomson KK (1996) Multiple serotonin receptor influences in the behavioral effects of hallucinogens in rats: the role of 5-HT1A and 5-HT2 receptors Psychology. UCSD, La JollaGoogle Scholar
- Titeler M, Lyon RA, Glennon RA (1988) Radioligand binding evidence implicates the brain 5-HT2 receptor as a site of action for LSD and phenylisopropylamine hallucinogens. Psychopharmacology (Berl) 94:213–216Google Scholar