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Differently lasting effects of prenatal and postnatal chronic clozapine/haloperidol on activity and memory in mouse
Jian Hong Wang1, Jian Zhen Yang, Fraser A W Wilson
1Key Laboratory of Animal Models and Human Disease Mechanisms and Section of Cognitive Brain Research, Kunming Institute of Zoology, Chinese Academy of Sciences, #32 Jiao Chang Dong Lu, Kunming, Yunnan, 650223, PR China.
Unlabelled:
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.
