The mGlu(2/3) receptor agonist LY379268 selectively blocks amphetamine ambulations and rearing.
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.
Cartmell
J
J
Neuroscience Research, Lilly Research Laboratories, Lilly Corporate Center, Eli Lilly and Company, Mail Drop 0510, Indianapolis, IN 46285, USA.
Monn
J A
JA
Schoepp
D D
DD
D000596:Amino Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000661:Amphetamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000502:physiology; D013239:Stereotyped Behavior / Q000187:drug effects; D014966:Xanthenes / Q000494:pharmacology
D000596:Amino Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; C118218:LY 379268; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D000661:Amphetamine