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


OBJECTIVE
A series of interaction studies using the serotonin (5-HT)(1A) antagonist WAY-100635 (1.0 mg/kg), the 5-HT(2A) antagonist M100907 (1.0 mg/kg), and the 5-HT(2C) 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-HT(2) receptors is solely responsible for hallucinogenic drug effects, these results support a role for 5-HT(1A) receptors in the effects of the indoleamine hallucinogen 5-MeO-DMT on locomotor activity and PPI in rats.
Krebs-Thomson
Kirsten
K
Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0804, USA.
Ruiz
Erbert M
EM
Masten
Virginia
V
Buell
Mahalah
M
Geyer
Mark A
MA
D000818:Animals; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D008732:Methoxydimethyltryptamines / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*
D008732:Methoxydimethyltryptamines; D044402:Receptor, Serotonin, 5-HT2A; D044282:Receptor, Serotonin, 5-HT1A; D008238:Lysergic Acid Diethylamide