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Published on: July 9, 2016
The mGlu(2/3) receptor agonist LY379268 selectively blocks amphetamine ambulations and rearing
J Cartmell1, J A Monn, D D Schoepp
1Neuroscience Research, Lilly Research Laboratories, Lilly Corporate Center, Eli Lilly and Company, Mail Drop 0510, Indianapolis, IN 46285, USA.
Abstract:
We have previously reported that the specific group II metabotropic glutamate receptor agonist LY379268 inhibited phencyclidine (PCP)-induced motor activations in rats, but had mixed effects on behaviors produced by amphetamine. Here, LY379268 (1 mg/kg subcutaneous (s.c.)) attenuated amphetamine-induced ambulations and rearing but did not alter amphetamine-evoked fine motor movements. Consistent with a mechanism involving mGlu(2/3) receptors, the inhibitory actions of LY379268 on ambulations and rearing were reversed by LY341495, a mGlu(2/3) receptor antagonist. These data further suggest antipsychotic actions of mGlu(2/3) receptor agonists with a low propensity for extra-pyramidal side effects.
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