MCPP-INDUCED ANXIETY IN THE LIGHT-DARK BOX IN RATS - A NEW METHOD FORSCREENING ANXIOLYTIC ACTIVITY

The activity of anxiolytic and other drugs in a light-dark test situat ion was studied in rats treated with the anxiogenic compound III-chlor ophenyl-piperazine (mCPP). mCPP 0.5 mg/kg significantly diminished the exploratory activity of the animals in the light compartment of the a pparatus. Drugs to be tested against mCPP-induced anxiety when studied alone (not in combination with mCPP) did not significantly alter the activity of rats in the light-dark apparatus, except yohimbine, which reduced the movement time values in the lit area. 1,4-Benzodiazepines [diazepam (0.1-4 mg/kg) and chlordiazepoxide (2-8mg/kg)], 5-HT2A/2C an tagonists [ritanserin (0.25-8 mg/kg) and deramciclane (0.5-8 g/k,)], t he 5-HT3 antagonist MDL-72222 (3mg/kg) and ethanol (2-4 mg/kg) signifi cantly reduced the effect of mCPP. A dose-dependent increase in the ex ploratory activity of mCPP-treated animals was found in the 2,3-benzod iazepine girisopam (2.5-5 mg/kg)-treated groups. Tofisopam, another 2, 3-benzodiazepine molecule, also showed activity against mCPP, although its effect was not statistically significant. The 5-HT1A partial agon ist buspirone was also active in the dose range of 0.25-0.5 mg/kg, whi le the 5-HT1A full agonist 8-OH-DPAT was the only drug with presumed a nxiolytic activity that clearly lacked any effect in this model. Imipr amine, amitriptyline, morphine, naloxone, haloperidol, clozapine, amph etamine, yohimbine, carbamazepine and diphenylhydantoin were not effec tive. We conclude that mCPP-induced anxiety in the light-dark box is a potent and useful method for screening and detecting anxiolytic activ ity of a wide range of compounds with various modes of action.