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.
Ninan
I
I
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Kulkarni
S K
SK
D000818:Animals; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018696:Neuroprotective Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity; D010880:Piperidines / Q000494:pharmacology; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects*; D016713:Ritanserin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D019956:Stereotypic Movement Disorder / Q000139:chemically induced / Q000188:drug therapy*
D006635:Histamine H2 Antagonists; D018696:Neuroprotective Agents; D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D016713:Ritanserin; C046301:seganserin; D016291:Dizocilpine Maleate; D007650:Ketanserin