Mar 12, 2013

The antipsychotic-like effects of the mGlu group III orthosteric agonist, LSP1-2111, involves 5-HT₁A signalling

J M WierońskaA Pilc


Several studies have suggested that modulation of the glutamatergic system via metabotropic glutamate receptors (mGlu) could be a new way to achieve antipsychotic-like activity. LSP1-2111, the group III mGlu receptor orthosteric agonist, with a high affinity towards mGlu4 receptors, was previously shown to exhibit antipsychotic-like action in animal models displaying positive symptoms of schizophrenia. Here, we decided to investigate the possible role of LSP1-2111 in models of negative (social interaction) and cognitive (NOR) symptoms of psychosis. We also investigated the involvement of 5-HT1A receptors in the LSP1-2111-induced antipsychotic effects. Apart from the above-mentioned models of negative and cognitive symptoms, MK-801 and amphetamine-induced hyperactivity tests, plus the DOI-induced head twitches in mice as models for positive symptoms of psychosis, were used in this part of the investigations. LSP1-2111 (0.5, 2, and 5 mg/ kg) dose-dependently inhibited MK-801-induced deficits in social interaction and NOR tests. The effects of the drug were antagonized by 5-HT1A antagonist, WAY100635 (0.1 mg/kg). A similar inhibition of LSP1-2111-induced effects was observed in models of positive symptoms of schizophrenia. Moreove...Continue Reading

Mentioned in this Paper

(R)-N-(2-(4(1H-indol-4-yl)-1-piperazinyl)-1-methylethyl)-N-(2-pyridyl) cyclohexanecarboxamide
Antipsychotic Effect
Neurobehavioral Manifestations
GRM4 gene
Serotonin 5-HT1A Receptor Antagonists

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