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

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2006-07, Vol.84 (3), p.468-478
• Main Authors: Wang, Jian Hong, Yang, Jian Zhen, Wilson, Fraser A.W., Ma, Yuan Ye
• Format: Article
• Language: English
• Subjects: Animals; Antipsychotic Agents - adverse effects; Avoidance Learning; Behavior, Animal - drug effects; Biological and medical sciences; Body Weight; Central Nervous System - drug effects; Central Nervous System - embryology; Clozapine; Clozapine - adverse effects; Female; Haloperidol; Haloperidol - adverse effects; Male; Maternal Exposure; Maze Learning; Medical sciences; Memory - drug effects; Mice; Neuropharmacology; Offspring; Open-field; Pharmacology. Drug treatments; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Step-through; Water-maze
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2006.06.010

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.