The effects of perinatal AZT exposure on the acoustic startle response in adult rats.
AZT (azidothymidine, zidovudine, ZDV) has become the standard medication to prevent the transmission of the human immunodeficiency virus from mother to fetus. The present study was designed to assess the acoustic startle response (ASR) in adult rats that had been perinatally exposed to AZT. Each litter was randomly assigned to a treatment group: nontreated, AZT 0, 50, 100 or 150 mg/kg. Once daily gastric intubation began prenatally between gestational day (G) 19 and 22 and then continued postnatally between postnatal day (PND) 2 and 20. Between PND75 and PND80, animals were tested for habituation to the acoustic stimuli and prepulse inhibition following a challenge of either saline or 1.0 mg/kg amphetamine (AMP) intraperitoneally. Amphetamine increased ASR and startle latencies throughout the session. The AZT100 dose increased ASR habituation. AZT treatment did not affect prepulse inhibition. Females treated with AZT150 continued to show high ASRs at the end of the startle session. AZT-treated animals showed a dose-dependent increase in peak latency, suggesting a possible abnormal conduction velocity. These effects are independent of handling and intubation effects. Therefore, perinatal AZT treatment results in long-term changes within the primary acoustic startle pathway.
Melnick
Susan M
SM
Department of Physiology and Pharmacology, State University of New York Downstate, 450 Clarkson Avenue, Box 29, Brooklyn 11203, USA.
Weedon
Jeremy
J
Dow-Edwards
Diana L
DL
D000161:Acoustic Stimulation; D000818:Animals; D000831:Animals, Newborn; D019380:Anti-HIV Agents / Q000633:toxicity*; D001306:Auditory Pathways / Q000187:drug effects* / Q000503:physiopathology; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D030762:Estrous Cycle / Q000187:drug effects / Q000502:physiology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology; D015215:Zidovudine / Q000633:toxicity*
D019380:Anti-HIV Agents; D015215:Zidovudine