Journal of Psychopharmacology
December 8, 2010
Liselore Koedood, Adam L. Halberstadt, Susan B. Powell et al.
212 citations
Psilocin, the active metabolite of psilocybin, acts as an agonist at 5-HT1A, 5-HT2A, and 5-HT2C receptors. In mice, psilocin induced head twitch response (HTR) via 5-HT2A receptors, as effects were absent in mice lacking that gene. In the behavioral pattern monitor (BPM), psilocin decreased locomotor activity, holepoking, and time in the chamber center; these effects were blocked by the 5-HT1A antagonist WAY-100635 but not by 5-HT2C antagonism or 5-HT2A gene deletion. 5-MeO-DMT produced similar BPM effects attenuated by WAY-100635. Psilocin and 5-MeO-DMT decreased path linearity via 5-HT2C and 5-HT1A receptors, respectively. 1-methylpsilocin induced HTR via 5-HT2A but was inactive in the BPM, suggesting greater pharmacological selectivity and potential as a therapeutic alternative to psilocybin.
Psychopharmacology
December 9, 2010
Adam L. Halberstadt, Virginia Lehmann-Masten, Mark A. Geyer et al.
35 citations
Loss of metabotropic glutamate 5 (mGlu5) receptor activity, either through gene deletion or pharmacological blockade, causes locomotor hyperactivity and reduced habituation in mice. The serotonergic hallucinogen and 5-HT2A agonist DOM (0.5 mg/kg) increased this hyperactivity, while the 5-HT2A antagonist M100907 (1.0 mg/kg) reduced it. M100907 (0.1 mg/kg) also blocked hyperactivity induced by the mGlu5-negative allosteric modulator MPEP. These findings indicate a functional interaction between mGlu5 and 5-HT2A receptors, suggesting mGlu5 receptors may mitigate the behavioral effects of 5-HT2A hallucinogens or that mGlu5 knockout mice have increased sensitivity to such agonists.
Psychopharmacology
February 14, 2019
Adam L. Halberstadt, Jochem V. F. Zee, Muhammad Chatha et al.
21 citations
Chronic treatment with an mGlu2/3 receptor agonist, LY379268, attenuated the head-twitch response (HTR) induced by the selective 5-HT2A agonist 25CN-NBOH in mice, even when tested 48 hours after the last dose. Acute LY379268 also reduced the HTR by about 50%. The HTR was completely blocked by a 5-HT2A antagonist but not by a 5-HT2C antagonist. In locomotor tests, acute LY379268 reduced PCP-induced hyperactivity in mice that had received chronic vehicle treatment, but only a trend for an interaction was seen in the chronic LY379268 group. These results support a functional interaction between mGlu2/3 and 5-HT2A receptors in modulating behavioral responses to 5-HT2A activation.