Repeated administration of 5-hydroxytryptamine 2C agonist MK212 produces a sensitization effect of antipsychotic activity

Weihai Chen, Xiaqing Wang, Minmin Yan, Yan Wang, Shixue Xie, Hong Li, Ming Li

Research output: Contribution to journalArticle

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-HT2C receptor agonists. The present study examined whether repeated activation of 5-HT2C receptor with a highly selective 5-HT2C 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 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.

Original languageEnglish (US)
Pages (from-to)985-993
Number of pages9
JournalIUBMB Life
Volume68
Issue number12
DOIs
StatePublished - Dec 1 2016

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Keywords

  • 5-hydroxytryptamine 2C receptor
  • MK212
  • MK801-induced hyperlocomotion
  • antipsychotics
  • conditioned avoidance response

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Clinical Biochemistry
  • Cell Biology

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