Differently lasting effects of prenatal and postnatal chronic clozapine/haloperidol on activity and memory in mouse offspring

Autor: Yuanye Ma, Jian Zhen Yang, Jianhong Wang, Fraser A.W. Wilson
Rok vydání: 2006
Předmět:
Zdroj: Pharmacology Biochemistry and Behavior. 84:468-478
ISSN: 0091-3057
Popis: We evaluated the behavioral effects of chronic haloperidol (HAL) and clozapine (CLO) during gestation and CNS development, compared with transient treatments that stopped 1–3 weeks before the test. Results : 1) Chronic HAL (6 mg/l in drinking water) but not HAL-withdrawal caused hypo-activity in open-field test on postnatal days (PNDs) 35, 42 and 56. However, hyper-activity was found in both CLO (90 mg/l) and CLO-withdrawal pups. 2) In the step-through test, retention performance was significantly higher in HAL-treated mice than in the controls on PND 42, as well as in withdrawal mice on PNDs 35 and 42. However, both chronic CLO (90 mg/l) exposure and CLO-withdrawal tended to improve the acquisition of memory. Furthermore, chronic CLO (180 mg/l) ameliorated scopolamine (3 mg/kg)-induced impairment of memory on PND 56. 3) In the water-maze test, both chronic HAL and HAL-withdrawal treatments significantly impaired performance on the 4th training day at PND 35, but not PNDs 42 and 56. Neither chronic CLO exposure nor CLO-withdrawal affected spatial memory. 4) Body weight following HAL/CLO administration decreased when compared with the controls during PND 21–35, but approached control levels at PND 40. Conclusion : HAL doesn't elicit permanent behavioral changes in offspring. By contrast, CLO had longer-lasting effects than HAL. The pups at age before PND 35 seem more sensitive to HAL/CLO than elder pups.
Databáze: OpenAIRE