Neurobehavioral Profile of F1 and F2 Generation Mice Following One Stage Zidovudine Exposure through Pregnancy and Lactation

Abstract

Background: Several animal studies have reported behavioural alteration in zidovudine exposed neonates, possibly resulting from an action of this drug on CNS targets. Purpose: The aim of the present study was to assess the neurobehavioral effects of one-stage zidovudine exposure during pregnancy and lactation in F 1 and F 2 generation of mice. Methods: Zidovudine (50 mg/ kg/ day) was administered to female Swiss mice given orally from day 8 of gestation through pregnancy and up to day 10 of postnatal life. Control mice were given equal volume of distilled water. F 1 generation mice on attainment of 60–90 days of age, underwent neurobehavioural testing for propensity towards anxiety and disturbances of learning and memory in the open field test, elevated plus-maze and Morris water-maze test. F 1 generation mice were crossed to produce F 2 mice. On attainment of 60–90 days, F 2 mice were also subjected to same neurobehavioral testings. Results: Perinatal Zidovudine exposure caused significant decreased mobility suggesting certain degree of anxiety in F 1 mice whereas the opposite is true in F2 mice. No derangement of motor activity was detected at maturity in the zidovudine exposed generation of mice in F 2 mice. Fl mice, in the elevated plus maze test showed reduced entry in open arm whereas the entries were increased in F 2 mice. Morris water maze test showed decreased learning capabilities in F 1 mice and regained learning ability in F 2 . Conclusion: This study suggests that neurobehavioral functions are affected in F 1 generation and recovery in F 2 generation. Recovery in F 2 generation beyond normal profiles could be due to activation of oncogenes as a result of chromosomal alterations. doi: 10.5214/ans.0972.7531.2008.150303 Competing interests: None. Source of Funding: None Received Date: 12 March 2008 Revised Date: 03 May 2008 Accepted Date: 08 June 2008