Effects of repeated quetiapine treatment on conditioned avoidance responding in rats

Authors

Jun Gao, Southwest University, Chongqing, China
Min Feng, Chinese Academy of Sciences, Beijing
Natashia Swalve, University of Nebraska–Lincoln
Collin Davis, University of Nebraska–LincolnFollow
Nan Sui, Chinese Academy of Sciences, BeijingFollow
Ming Li, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

12-14-2015

Citation

Published in European Journal of Pharmacology 769 (December 15, 2015), pp. 154–161; doi: 10.1016/j.ejphar.2015.11.011

Comments

Copyright © 2015 Elsevier B.V. Used by permission.

Abstract

The present study characterized the behavioral mechanisms of avoidance–disruptive effect of quetiapine in the conditioned avoidance response test under two behavioral testing (2 warning signals vs. 1 warning signal) and two drug administration conditions (subcutaneous vs. intravenous). In Experiments 1 and 2, well-trained adult male Sprague-Dawley rats were tested under the subcutaneous (s.c.) quetiapine treatment (5.0, 15.0, 25.0, 50.0 mg/kg) for 7 days in a novel procedure consisting of two conditioned stimuli (CS) (white noise serving as CS1 and pure tone as CS2). Only the highest dose (50.0 mg/kg) produced a persistent suppression of the avoidance response without impairing the escape response. The magnitude of suppression of the CS1 avoidance was similar to that of CS2 avoidance. No significant group difference was found in the quetiapine (15.0 mg/kg, s.c.) challenge test, indicating a lack of a long-term quetiapine effect. In Experiment 3, well-trained rats were tested under the intravenous (i.v.) quetiapine treatment (3.0, 9.0, 15.0 mg/kg) for 5 days and challenged with quetiapine (6.0 mg/kg, i.v. followed by 9.0 mg/kg, s.c.). Only the white noise was used as the CS. Similar to what was being observed in Experiments 1 and 2, intravenously administered quetiapine dose-dependently suppressed avoidance responding during the drug test days, but did not alter drug sensitivity in the challenge days. Thus, quetiapine does not appear to show a preferential inhibition of the avoidance response to a less salient stimulus; and prior quetiapine treatment (s.c. and i.v.) does not cause a sensitization or tolerance to quetiapine.