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.
MeSH terms
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Amino Acids / antagonists & inhibitors
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Amino Acids / pharmacology*
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Amphetamine / antagonists & inhibitors*
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Amphetamine / pharmacology
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Animals
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Bridged Bicyclo Compounds, Heterocyclic / antagonists & inhibitors
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
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Dose-Response Relationship, Drug
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Drug Interactions
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Excitatory Amino Acid Agonists / pharmacology*
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Excitatory Amino Acid Antagonists / pharmacology
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Male
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Motor Activity / drug effects*
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Rats
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Rats, Sprague-Dawley
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Receptors, Metabotropic Glutamate / agonists*
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Receptors, Metabotropic Glutamate / physiology
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Stereotyped Behavior / drug effects
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Xanthenes / pharmacology
Substances
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Amino Acids
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Bridged Bicyclo Compounds, Heterocyclic
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Excitatory Amino Acid Agonists
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Excitatory Amino Acid Antagonists
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LY 341495
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LY 379268
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Receptors, Metabotropic Glutamate
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Xanthenes
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metabotropic glutamate receptor 2
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metabotropic glutamate receptor 3
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Amphetamine