Locomotor activity detects subunit-selective effects of agonists and decahydroisoquinoline antagonists at AMPA/kainic acid ionotropic glutamate receptors in adult rats.

Rationale: In vitro studies have identified a series of decahydroisoquinoline compounds with differential selectivity for the subunits that comprise AMPA/kainic acid receptors. Compounds have been identified that have preferential activity at AMPA receptors (LY302679), whereas others (LY377770) have affinity for GluR5-kainic acid preferring subunit, which is activated by ATPA and kainic acid.

Objectives: These studies set out to determine if locomotor activity could differentiate these profiles in vivo.

Neurotrophic actions of the novel AMPA receptor potentiator, LY404187, in rodent models of Parkinson's disease.

Recent developments in the molecular biology and pharmacology of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors has led to the discovery of selective, potent and systemically active AMPA receptor potentiators. These molecules enhance synaptic transmission and evidence suggests that they play important roles in plasticity and cognitive processes. Activation of AMPA receptors also increases neuronal activation and activity-dependent signalling, which may increase brain-derived neurotrophic factor (BDNF) expression and enhance cell proliferation in the brain.

Evaluation of the mGluR2/3 agonist LY379268 in rodent models of Parkinson's disease.

The aim of the present studies was to examine the ability of a potent, systemically active, selective Group II mGlu receptor (mGluR2/3) agonist, 1R,4R,5S,6R-2-oxa-4-minobicyclo[3.1.0.