Risperidone attenuates MK-801-induced hyperlocomotion in mice via the blockade of serotonin 5-HT 2A/2C receptors.
Glutamate N-methyl-D-aspartate (NMDA) receptor antagonists, like phencyclidine (PCP), elicit schizophrenia-like symptoms in humans and behavioral abnormalities in animals, such as hyperactivity. We investigated the effect of the atypical antipsychotic risperidone on hyperlocomotion produced in mice by 5R,10S-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine hydrogen maleate (MK-801), an NMDA receptor antagonist. MK-801 (0.125, 0.25, 0.50 mg/kg) dose-dependently increased the total distance traveled in an open field during a 90 min period in mice. The increase in MK-801 (0.25 mg/kg)-induced total distance traveled was attenuated by pretreatment with risperidone at doses that alone had no effect on spontaneous locomotor activity. Furthermore, (+/-)-1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), a serotonin 5-HT(2A/2C) receptor agonist, at the doses that failed to change spontaneous locomotor activity or hyperlocomotion induced by MK-801, reversed the attenuation by risperidone. The serotonin 5-HT(2A/2C) receptor antagonist, ritanserin, enhanced the inhibitory effect of risperidone. These findings indicate that risperidone attenuates MK-801-induced hyperlocomotion in mice by blocking serotonin 5-HT(2A/2C) receptors.
Su
Yun-Ai
YA
Institute of Mental Health, Peking University, No. 51 Hua Yuan Bei Road, Beijing 100083, China.
Si
Tian-Mei
TM
Zhou
Dong-Feng
DF
Guo
Chun-Mei
CM
Wang
Xiao-Dong
XD
Yang
Yang
Y
Shu
Liang
L
Liang
Jian-Hui
JH
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal; D016291:Dizocilpine Maleate; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects* / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects* / Q000378:metabolism; D018967:Risperidone / Q000008:administration & dosage / Q000494:pharmacology*; D016713:Ritanserin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D000662:Amphetamines; D014150:Antipsychotic Agents; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D016713:Ritanserin; D016291:Dizocilpine Maleate; D018967:Risperidone; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine