5-HT2A receptor antagonists block MK-801-induced stereotypy and hyperlocomotion

The present study was undertaken to examine the effect of 5-HT2A receptor antagonists on MK-801 (5-methyl-10,11-dihydro-5H-dibenzo (a,d) cyclohepten-5,10-imine)-induced stereotypy and hyperlocomotion. MK-801 (0.1, 0.25 and 0.5 mg/kg) dose-dependently increased stereotypy and locomotion in mice. The 5-HT2A receptor antagonists, ketanserin (2.5, 5 and 10 mg/kg) and ritanserin (0.5, 1 and 2 mg/kg), dose-dependently blocked MK-801 (0.5 mg/kg)-induced hyperlocomotion. Only the higher dose (2 mg/kg) of seganserin could block locomotor activity. Similarly, ketanserin (2.5, 5 and 10 mg/kg), ritanserin (1 and 2 mg/kg) and seganserin (0.5, 1 and 2 mg/kg) dose-dependently blocked MK-801 (0.5 mg/kg)-induced stereotypy. The results suggest the involvement of 5-HT2A receptors in MK-801-induced stereotypy and hyperlocomotion. The lack of effect on spontaneous locomotion further suggests that 5-HT2A receptor antagonists will be less prone to induce psychomotor side-effects.