title: Repeated administration of 5-hydroxytryptamine 2C agonist MK212 produces a sensitization effect of antipsychotic activity.
abstract: 5-Hydroxytryptamine 2C (5-HT2C) receptor agonists have been suggested to possess an antipsychotic activity in several acute preclinical tests of antipsychotic drugs with low extra-pyramidal side effect liability. However, little is known about the long-term effect associated with chronic use of 5-HT2Creceptor agonists. The present study examined whether repeated activation of 5-HT2Creceptor with a highly selective 5-HT2Creceptor agonist MK212 would induce a long-term change in its antipsychotic-like activity (either a sensitization or tolerance) in the conditioned avoidance response and MK801-induced hyperlocomotion tests. Sprague-Dawley rats were first tested under the intraperitoneal (i.p.) treatment of MK212 (0.25, 0.5, 1.0 mg/kg) for 5 consecutive days. Three days later, when all rats were injected with a low dose of MK 212 (0.25 mg/kg) and tested for avoidance responding, rats that had been pretreated with 1.0 and 0.5 mg/kg MK212 made significantly fewer avoidance responses than those that had been treated with vehicle (0.9% saline). However, this past drug exposure-induced group difference was not significant in the MK801-induced hyperlocomotion test. Overall, results from this study suggest that repeated treatment of MK212 is capable of inducing a dose-dependent sensitization of antipsychotic activity in conditioned avoidance response. The discrepancy in sensitization of MK212 in CAR and MK801-induce hyperlocomotion may be related to the different mechanism underlying the effect of MK212 in these two tests. © 2016 IUBMB Life, 68(12):985-993, 2016.
authors: Key Laboratory of Cognition and Personality (Southwest University), Ministry of Education, China.|Faculty of Psychology, Southwest University, Chongqing, China.
authors: Weihai
authors: W
authors: Chen
authors: Key Laboratory of Cognition and Personality (Southwest University), Ministry of Education, China.|Faculty of Psychology, Southwest University, Chongqing, China.
authors: Xiaqing
authors: X
authors: Wang
authors: Key Laboratory of Cognition and Personality (Southwest University), Ministry of Education, China.|Faculty of Psychology, Southwest University, Chongqing, China.
authors: Minmin
authors: M
authors: Yan
authors: Key Laboratory of Cognition and Personality (Southwest University), Ministry of Education, China.|Faculty of Psychology, Southwest University, Chongqing, China.
authors: Yan
authors: Y
authors: Wang
authors: Key Laboratory of Cognition and Personality (Southwest University), Ministry of Education, China.|Faculty of Psychology, Southwest University, Chongqing, China.
authors: Shixue
authors: S
authors: Xie
authors: Key Laboratory of Cognition and Personality (Southwest University), Ministry of Education, China.|Faculty of Psychology, Southwest University, Chongqing, China.
authors: Hong
authors: H
authors: Li
authors: Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE 68588-0308, USA.
authors: Ming
authors: M
authors: Li
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D001362:Avoidance Learning; D003213:Conditioning, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011719:Pyrazines / Q000008:administration & dosage*; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage*
chemical_list: D014150:Antipsychotic Agents; D011719:Pyrazines; D017366:Serotonin Receptor Agonists; C014896:6-chloro-2-(1-piperazinyl)pyrazine
keywords: 5-hydroxytryptamine 2C receptor; MK212; MK801-induced hyperlocomotion; antipsychotics; conditioned avoidance response