INTERACTIONS BETWEEN IFENPRODIL AND DIZOCILPINE ON MOUSE BEHAVIOR IN MODELS OF ANXIETY AND WORKING-MEMORY

The N-methyl-D-aspartate (NMDA) receptor polyamine site antagonist, if enprodil, had no effect on spontaneous alternation or locomotor activi ty in the Y-maze when given alone. The NMDA receptor/ion channel block er, dizocilpine, induced a deficit in spontaneous alternation, but whe n ifenprodil was co-administered with dizocilpine, it showed a strong tendency to attenuate the dizocilpine-induced deficit. In the plus-maz e, ifenprodil had an anxiolytic profile which was accompanied by an in crease in locomotion. Dizocilpine had an anxiolytic profile in this mo del and increased locomotor activity. When co-administered with dizoci lpine, ifenprodil reduced both the anxiolytic and locomotor effects of dizocilpine. When co-administered with ifenprodil, cyclopentyladenosi ne (CPA) and 1,3-dipropyl-8-cyclopentylxanthine (CPX) reduced the anxi olytic effect of ifenprodil. CPA and CPX in combination did not revers e the anxiolytic effect of ifenprodil. It is concluded that NMDA antag onists with different sites of action can show distinct behavioural pr ofiles, with dizocilpine but not ifenprodil inducing a deficit in work ing memory, while both are anxolytic. Blockade of NMDA receptors by if enprodil, however, can preclude any response to dizocilpine. The anxio lytic activity of ifenprodil may involve the release of purines acting at adenosine receptors.