Activation of Metabotropic Glutamate Receptor (mGlu2) and Muscarinic Receptors (M1, M4, and M5), Alone or in Combination, and Its Impact on the Acquisition and Retention of Learning in the Morris Water Maze, NMDA Expression and cGMP Synthesis

Experiments

Items

Instructions

1
Mice were trained to find a hidden platform in a circular pool using spatial cues. Training consisted of 5 days with 4 trials per day, drugs administered 30 min before MK-801 and 30 min before first trial each day. Escape latency measured.
2
Retention trial conducted the day after the acquisition phase, no drugs administered. Parameters related to NE zone and platform zone measured.
3
Mice receiving highest doses of drugs sacrificed post-MWM, tissues collected for further analysis. Tissues stored at -80°C until analysis.
4
Homogenized samples in lysis buffer, centrifuged, crude synaptosomal fractions sonicated. Protein concentrations measured, samples prepared for Western blotting and cGMP ELISA.

Methodologies

Animals kept under standard conditions with food and water available ad libitum. Intraperitoneal administration of drugs at a volume of 10 mL/kg. Procedures conducted in accordance with European Communities Council Directive and Polish legislative acts.
First set of experiments: Drugs administered alone to determine dose-dependent effects on MK-801-induced dysfunction in MWM test. Dose ranges: VU0357017 (0.25-1 mg/kg), VU0152100 (0.05-1 mg/kg), VU0238429 (1-20 mg/kg), LY487379 (0.5-5 mg/kg).
Second part: Activity of simultaneous administration of LY487379 with each muscarinic activator tested. Combinations administered at inactive, intermediate, and highest doses.