Perinatal AZT exposure alters the acoustic and tactile startle response to 8-OH-DPAT and apomorphine in adult rats.
The present study was designed to assess the dopaminergic and serotonergic contributions of the acoustic startle response (ASR) and the tactile startle response (TSR) in adult rats that had been perinatally exposed to AZT (azidothymidine, zidovudine; an antiretroviral agent). Each dam was randomly assigned to a treatment group: non-treated, AZT0, 100 or 150 mg/kg. Once daily gastric intubation began prenatally on gestational day (G) 19 and continued to G22 and then the pups were intubated between postnatal day (PND) 2-20. On PND60, animals were tested for responses to both acoustic and tactile stimuli following a challenge of vehicle, 0.25 or 0.5 mg/kg 8-OH-DPAT, a 5-HT(1A) agonist, or 0.75 or 2.0 mg/kg apomorphine (APO, a dopaminergic agonist) IP. Both DPAT and APO increased startle magnitude as expected. Additionally, perinatal AZT exposure enhanced startle responses following both DPAT and APO, an effect not due to perinatal handling or intubation. Similarly, perinatal AZT increased tactile responses following drug challenge in a gender-specific manner. Perinatal AZT also prolonged startle latencies, a change which may indicate that perinatal AZT alters conduction velocity. Therefore, the administration of AZT during the perinatal period results in long-term functional alterations within the startle reflex pathways.
Department of Physiology and Pharmacology, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
Susan M
SM
Melnick
Jeremy
J
Weedon
Diana L
DL
Dow-Edwards
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D019380:Anti-HIV Agents / Q000633:toxicity; D001058:Apomorphine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D008297:Male; D010812:Physical Stimulation / Q000379:methods; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012737:Sex Factors; D015215:Zidovudine / Q000633:toxicity*
D019380:Anti-HIV Agents; D018491:Dopamine Agonists; D017366:Serotonin Receptor Agonists; D015215:Zidovudine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D001058:Apomorphine