Lorazepam attenuates the behavioral effects of dizocilpine

To characterize the potential interaction between the excitatory and inhibi tory neurotransmitter systems, the effects of dizocilpine, CPP, and lorazep am on open-field behavior and pentylenetetrazol-induced seizures were evalu ated in mice. Dizocilpine (0.01-0.1 mg/kg), CPP (1-10 mg/kg), or vehicle wa s administered intraperitoneally 15 min prior to lorazepam (0.2-2 mg/kg) or vehicle. Behavioral monitoring began 25 min after the lorazepam injection. Upon completion of testing, unrestrained mice were infused intravenously w ith pentylenetetrazole until the onset of a full tonic-clonic seizure. The highest dose of dizocilpine by itself significantly increased the average d istance traveled, the number of rears, and the number of stereotypies durin g the test period. Lorazepam alone dose dependently decreased activity on a ll behavioral parameters. Lorazepam also completely antagonized the hyperac tivity produced by dizocilpine when the two compounds were coadministered. This antagonism is most likely due to an interaction in the regulation of d opaminergic tone which underlies motor activity. Lorazepam exerted a dose-d ependent anticonvulsant effect. Dizocilpine alone had no effect on seizure induction and did not potentiate the anticonvulsive effect of lorazepam whe n coadministered with lorazepam. CPP reduced the number of rears and the nu mber of stereotypies during the test period. CPP did not alter the pentylen etetrazol-induced seizure threshold and did not influence the anticonvulsan t effect of lorazepam. (C) 1998 Elsevier Science Inc.