The differential effects of prenatal stress in rats on the acoustic startle reflex under baseline conditions and in response to anxiogenic drugs

Abstract.

Rationale: The prenatal stress syndrome (PS) is characterized by exaggerated behavioral and physiological responses to stressful stimuli and anxiogenic agents. Objectives: To characterize the behavioral effects of PS on the acoustic startle reflex (ASR) and to determine the possible role of PS-induced alterations in noradrenergic control of ASR by determining the effects of the α₂-adrenoceptor antagonists, yohimbine, idazoxan, and RS79948–197. Methods: PS was induced by exposing pregnant dams to a mild stressor of handling and saline injection (0.1 ml, s.c.) from gestational days 14 to 21. Control dams were left undisturbed throughout pregnancy. Using adult male offspring, all ASR studies consisted of either a 30- or 60-min testing period containing 60 or 120 acoustic startle stimuli trials (95 dB, 50 ms noise burst) at a fixed intertrial interval of 30 s after a 5-min acclimation period. For drug studies, a 3-day repeated measures design was implemented. Results: With the exception of the response to the first startle stimulus on the first day of testing, there were no significant differences in baseline ASR between control and PS offspring. Low doses of yohimbine, idazoxan, and RS79948–197 were anxiogenic in the ASR test in both control and PS offspring. PS offspring were less responsive to higher doses of yohimbine (5 mg/kg) and idazoxan (8 mg/kg) but did not differ from control in their responses to any dose of RS79948–197. Conclusions: Anxiogenic effects of yohimbine, idazoxan, and RS79978–197, likely mediated via α₂-adrenoceptor blockade, are similar in control and PS rats. Differences between control and PS rats occurred in the response to higher doses of yohimbine and idazoxan. Non-specific effects of these drugs, such as actions at 5HT_1A receptors, may cause their behavioral profile to be altered by PS, and to differ from the highly selective RS79948–197.