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


CONCLUSIONS
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.
Wang
Jian Hong
JH
Key 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.
Yang
Jian Zhen
JZ
Wilson
Fraser A W
FA
Ma
Yuan Ye
YY
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001362:Avoidance Learning; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight; D002490:Central Nervous System / Q000187:drug effects / Q000196:embryology; D003024:Clozapine / Q000009:adverse effects*; D005260:Female; D006220:Haloperidol / Q000009:adverse effects*; D008297:Male; D018811:Maternal Exposure; D018782:Maze Learning; D008568:Memory / Q000187:drug effects*; D051379:Mice
D014150:Antipsychotic Agents; D003024:Clozapine; D006220:Haloperidol