Chronic treatment with a metabotropic mGlu23 receptor agonist diminishes behavioral response to a phenethylamine hallucinogen.
There is evidence that mGlu23 receptors regulate 5-HT We first conducted a dose response of 25CN-NBOH (0.1, 0.3, 1, 3, or 10 mgkg) to confirm the effects on head-twitch response (HTR) and then blockade studies with either the M100907 (0.1 mgkg) or SB242084 (0.1, 0.3, or 1 mgkg) to determine the contribution of 5-HT2A and 5-HT2C to 25CN-NBOH-induced HTR, respectively. To determine whether an mGlu23 agonist could block 25CN-NBOH-induced HTR, mice were pretreated with vehicle or LY379268 (0.1, 1, or 10 mgkg) prior to 25CN-NBOH, and HTR was assessed. The effects of chronic LY379268 on 5-HT2A agonist-induced HTR were evaluated by treating mice with either vehicle or LY379268 (10 mgkg) for 21 days and measuring 25CN-NBOH-induced HTR 48 h after the final LY379268 treatment. The following day (72 h after the final LY379268 treatment), the ability of acute LY379268 to block PCP-induced locomotor activity was assessed. 25CN-NBOH dose-dependently increased the HTR, a 5-HT These data are consistent with a functional interaction between mGlu23 and 5-HT