Moderate-level prenatal alcohol exposure enhances acoustic startle magnitude and disrupts prepulse inhibition in adult rhesus monkeys

Abstract

Background: Prenatal alcohol exposure can contribute to a wide range of neurodevelopmental impairments in children and adults including behavioral and neuropsychiatric disorders. In rhesus monkeys, we examined whether moderate-level prenatal alcohol exposure would alter acoustic startle responses and prepulse inhibition (PPI) of the acoustic startle. PPI is a highly quantifiable measure of inhibitory neural processes or sensorimotor gating associated with neuropsychiatric disorders.

Methods: Acoustic startle and PPI of the acoustic startle were tested in 37 adult rhesus monkeys (Macaca mulatta) from 4 experimental conditions: (i) moderate-level prenatal alcohol-exposed, (ii) prenatally stressed, (iii) moderate-level prenatal alcohol-exposed + prenatally stressed, and (iv) sucrose controls.

Results: Prenatal alcohol-exposed monkeys showed a higher magnitude of acoustic startle response and disrupted PPI compared with monkeys not exposed to alcohol prenatally. Monkeys in all conditions showed higher hypothalamic-pituitary-adrenocortical (HPA) axis responses after undergoing the startle procedure, but HPA responses were unrelated to startle response magnitude, latency, or PPI.

Conclusions: Finding altered PPI in monkeys prenatally exposed to a moderate dose of alcohol suggests that reduced sensorimotor gating is 1 effect of prenatal alcohol exposure. Because reduced sensorimotor gating is observed in many neuropsychiatric disorders, sensorimotor gating deficits could be an aspect of the comorbidity between fetal alcohol spectrum disorder and mental health conditions.

Keywords: Acoustic Startle Response; Fetal Alcohol Spectrum Disorder; Inhibitory Control; Mental Health; Prepulse Inhibition.

Fig. 1

Mean startle magnitudes (top panel) and latencies (bottom panel) for the first four trials with a separate curve for each prenatal treatment group. Bars are +/− 1 se of the mean.

Fig. 2

Mean startle magnitudes as a function of prepulse intervals (none, 45, 120 and 500ms) with a separate curve for each prenatal treatment group. Bars are +/− 1 se of the mean.

Fig. 3

Mean startle latencies as a function of prepulse intervals (none, 45, 120 and 500 ms) with a separate curve for each prenatal treatment group. Bars are +/− 1 se of the mean.

Fig.4

Mean plasma ACTH (pg/ml) at baseline (1 week before startle testing) and after startle testing (immediately following the 45 min startle session) as a function of prenatal treatment group. Bars are +/− 1 se of the mean. ACTH, adrenocorticotrophic hormone.