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-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. © 2016 IUBMB Life, 68(12):985-993, 2016.

journal_name

IUBMB Life

journal_title

IUBMB life

authors

Chen W,Wang X,Yan M,Wang Y,Xie S,Li H,Li M

doi

10.1002/iub.1580

subject

Has Abstract

pub_date

2016-12-01 00:00:00

pages

985-993

issue

12

eissn

1521-6543

issn

1521-6551

journal_volume

68

pub_type

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