Anticonflict effects of a competitive NMDA receptor antagonist and a partial agonist at strychnine-insensitive glycine receptors.

Abstract

Using the conflict drinking Vogel test in rats as a model, in the present study we examined the anxiolytic-like activity of DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 37849), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist and 1-aminocyclopropanecarboxylic acid (ACPC), a partial agonist at strychnine-insensitive glycine receptors associated with the NMDA receptor complex, after their intraperitoneal (i.p.) and intrahippocampal (IHP) administration. CGP 37849, administered in doses of 1.25-5 mg/kg i.p., produced an anticonflict effect in a dose-dependent manner, but was inactive when injected in doses of 0.01-0.1 micrograms IHP. At the same time, when administered in higher doses (10 mg/kg i.p. or 0.3 micrograms IHP), that drug induced motor impairment. On the other hand, ACPC exhibited an anxiolytic-like activity after both i.p. (100-200 mg/kg) and IHP (3-30 micrograms) administration. These results, as well as the literature data on the lack of motor-impairing effects of ACPC, indicate that the latter drug seems to be more advantageous than CGP 37849 as a potential therapeutic agent in the treatment of anxiety disorders. Furthermore, they also show that the hippocampus may be one of the neuroanatomical sites of the anxiolytic-like effect of ACPC, but not of CGP 37849.

• Authors: E Przegaliński, E Tatarczyńska, A Dereń-Wesołek, E Chojnacka-Wójcik
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 54 Issue 1 Pg. 73-7 (May 1996) ISSN: 0091-3057 [Print] United States
• PMID: 8728541 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acids
• Amino Acids, Cyclic
• Anti-Anxiety Agents
• Excitatory Amino Acid Antagonists
• Glycine Agents
• Receptors, Glycine
• Receptors, N-Methyl-D-Aspartate
• 2-amino-4-methyl-5-phosphono-3-pentenoic acid
• 1-aminocyclopropane-1-carboxylic acid
• 2-Amino-5-phosphonovalerate
• Strychnine

Topics

• 2-Amino-5-phosphonovalerate (analogs & derivatives, pharmacology)
• Amino Acids (pharmacology)
• Amino Acids, Cyclic
• Animals
• Anti-Anxiety Agents (pharmacology)
• Behavior, Animal (drug effects, physiology)
• Brain (anatomy & histology, physiology)
• Conflict, Psychological
• Dose-Response Relationship, Drug
• Drinking Behavior (drug effects)
• Electroshock
• Excitatory Amino Acid Antagonists (pharmacology)
• Glycine Agents (pharmacology)
• Hippocampus (physiology)
• Injections
• Injections, Intraperitoneal
• Male
• Rats
• Rats, Wistar
• Receptors, Glycine (agonists, antagonists & inhibitors)
• Receptors, N-Methyl-D-Aspartate (agonists, antagonists & inhibitors)
• Strychnine (pharmacology)