A role for noradrenergic transmission in the actions of phencyclidine and the antipsychotic and antistress effects of mGlu2/3 receptor agonists.
Annals of the New York Academy of Sciences November 1, 2003 Chad J Swanson, Darryle D Schoepp
Activating mGlu2/3 receptors with the drug LY379268 reduces the behavioral effects of phencyclidine (PCP) in rats, and this effect is linked to changes in norepinephrine release. In rats undergoing brain microdialysis, LY379268 blocked PCP-induced hyperactivity for about three hours and transiently reduced PCP-induced dopamine release. PCP-induced norepinephrine release was reduced in a way that matched the timing of the behavioral reduction. Separately, the norepinephrine-related drugs clonidine (which reduces norepinephrine activity) blocked PCP behaviors, while reboxetine (which increases norepinephrine) worsened them. LY379268 reversed PCP effects even when reboxetine was present. These results suggest that mGlu2/3 receptor activation can normalize stress-related pathways affected by PCP.