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

Pharmacol Biochem Behav. 1996 May;54(1):73-7. doi: 10.1016/0091-3057(95)02157-4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / analogs & derivatives
  • 2-Amino-5-phosphonovalerate / pharmacology
  • Amino Acids / pharmacology
  • Amino Acids, Cyclic*
  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology*
  • Brain / anatomy & histology
  • Brain / 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*
  • Receptors, Glycine / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / agonists*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Strychnine / pharmacology

Substances

  • 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