The roles of 5-HT1A and 5-HT2 receptors in the effects of 5-MeO-DMT on locomotor activity and prepulse inhibition in rats
- 434 Downloads
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
This work was supported by National Institute on Drug Abuse Award R02 DA02925 and the Veterans Affairs VISN 22 Mental Illness Research, Education, and Clinical Center. M. A. Geyer holds an equity position in San Diego Instruments. These studies were conducted while E. M. Ruiz was conducting an externship from the School of Pharmacy, University of Utrecht, The Netherlands. These experiments comply with the current laws of the United States.
- 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