title: Differently lasting effects of prenatal and postnatal chronic clozapine/haloperidol on activity and memory in mouse offspring.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jian Hong
authors.initials: JH
authors.lastname: Wang
authors.forename: Jian Zhen
authors.initials: JZ
authors.lastname: Yang
authors.forename: Fraser A W
authors.initials: FA
authors.lastname: Wilson
authors.forename: Yuan Ye
authors.initials: YY
authors.lastname: Ma
mesh_terms: 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
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine; D006220:Haloperidol