THE ANTIEPILEPTIC AGENT GABAPENTIN (NEURONTIN) POSSESSES ANXIOLYTIC-LIKE AND ANTINOCICEPTIVE ACTIONS THAT ARE REVERSED BY D-SERINE

This report describes the activity of the antiepileptic agent gabapent in (Neurontin) in animal models predictive of anxiolysis and analgesia . Gabapentin displayed anxiolytic-like action in the rat conflict test , the mouse light/dark box and the rat elevated X-maze with respective minimum effective doses (MEDs) of 3, 10 and 30 mg/kg. Furthermore, ga bapentin also induced behavioural changes suggestive of anxiolysis in the marmoset human threat test with a MED of 30 mg/kg. In the rat form alin test of tonic nociception, gabapentin dose-dependently (30-300 mg /kg) and selectively blocked the late phase with a MED of 100 mg/kg. H owever, it failed to block carrageenan-induced paw oedema. The intrace rebroventricular (ICV) administration of the glycine/NMDA receptor ago nist D-Serine, dose-dependently (10-100 mu g/animal) reversed the anti nociceptive action of gabapentin (200 mg/kg, SC). D-Serine (30 mu g/an imal, ICV) also reversed the anxiolytic-like effects (in the light/dar k box and the rat elevated X-maze) of gabapentin (30 mg/kg). In contra st, L-Serine (100 mu g, ICV) failed to block the antinociceptive actio n of gabapentin. The antinociceptive action of (+)-HA-966 (25 mg/kg, S C), a partial agonist at the glycine/NMDA receptor, was reversed by D- Serine (100 mu g/animal, ICV). However, D-Serine (100 mu g/animal, ICV ) failed to affect the antinociceptive action of a competitive NMDA re ceptor antagonist CGS 19755 (3 mg/kg, SC). Gabapentin has negligible a ffinity for the strychnine insensitive [H-3]glycine binding site. This indicates that the interaction between gabapentin and D-Serine may no t involve the NMDA receptor complex. Gabapentin may represent a novel type of anxiolytic and analgesic agent.