Dizocilpine does not prevent the development of tolerance to the anxiolytic effects of diazepam in rats

The non-competitive NMDA receptor antagonist, dizocilpine (0.25 mg/kg), has previously been shown to block the development of tolerance to the sedativ e effects of diazepam (2 mg/kg). Since there is considerable evidence that different mechanisms underlie the development of tolerance to the sedative and anxiolytic effects of diazepam, the present experiment examined whether dizocilpine would block the development of tolerance to diazepam's anxioly tic effects. Rats tested after an acute dose of diazepam (2 mg/kg) showed a n anxiolytic effect, measured by an increase in the time spent in social in teraction, whereas those tested after 21 days of treatment had scores equal to the control group. This development of tolerance was not blocked by con comitant administration of dizocilpine (0.25 mg/kg). Thus, these results pr ovide further evidence that the mechanism underlying tolerance to the anxio lytic effects of diazepam is different from that underlying tolerance to th e sedative effects. (C) 1999 Published by Elsevier Science B.V. All rights reserved.