Effects of repeated quetiapine treatment on conditioned avoidance responding in rats

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.

Assessing NH300094, a novel dopamine and serotonin receptor modulator with cognitive enhancement property for treating schizophrenia

“…It is suggested that simultaneous blocking of dopamine D 2 and 5-HT 2A receptors improves the efficacy of antipsychotic drugs in patients with schizophrenia and reduces the risk of extrapyramidal symptoms (EPS) ( Andree et al, 1997 ; Kusumi et al, 2015 ). The conditioned avoidance response study is a well-established preclinical antipsychotic animal model ( Wadenberg et al, 2000 ; Gao et al, 2015 ). Antipsychotic drugs can selectively suppress the conditioned avoidance response of rats.…”

Brain Targeting of Quetiapine Fumarate via Intranasal Delivery of Loaded Lipospheres: Fabrication, In-Vitro Evaluation, Optimization, and In-Vivo Assessment

“…Dosing of animals orally was done by the method of Kuentz, 2012 [48][49][50][51][52], and was followed for all the intranasal drug delivery of quetiapine. The dose of 20 mg/kg was used for the study [51,53].…”