Repeated Administration of 5-Hydroxytryptamine 2C Agonist MK212 Produces a Sensitization Effect of Antipsychotic Activity

Authors

• Weihai Chen, Southwest University, Chongqing, ChinaFollow
• Xiaqing Wang, Southwest University, Chongqing, China
• Minmin Yan, Southwest University, Chongqing, China
• Yan Wang, Southwest University, Chongqing, China
• Shixue Xie, Southwest University, Chongqing, China
• Hong Li, Southwest University, Chongqing, ChinaFollow
• Ming Li, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

10-2016

Citation

IUBMB Life. 2016 Dec;68(12):985-993.

doi: 10.1002/iub.1580

Comments

Copyright 2016 International Union of Biochemistry and Molecular Biology

Link to free access copy via PubMed Central

Via: https://www.ncbi.nlm.nih.gov/pubmed/27797140

To target: https://doi.org/10.1002/iub.1580

Abstract

5-Hydroxytryptamine 2C (5-HT_2C) 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-HT_2C receptor agonists. The present study examined whether repeated activation of 5-HT_2C receptor with a highly selective5-HT_2C receptor 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 MK212 (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 antipsychoticactivity in conditioned avoidance response. The discrepancy insensitization of MK212 in CAR and MK801-induce hyperlocomotion may be related to the different mechanism underlying the effect of MK212 in these two tests.