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 of the acoustic startle (PPI). 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 was tested in 37 adult rhesus monkeys (Macaca mulatta) from four experimental conditions: (a) moderate level prenatal alcohol-exposed, (b) prenatally-stressed, (c) moderate level prenatal alcohol-exposed + prenatally-stressed, and (d) 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 HPA-axis responses after undergoing the startle procedure, but HPA responses were unrelated to startle response magnitude, latency, or PPI. Conclusion Finding altered PPI in monkeys prenatally exposed to a moderate dose of alcohol suggests that reduced sensorimotor gating is one effect of prenatal alcohol exposure. Because reduced sensorimotor gating is observed in many neuropsychiatric disorders, sensorimotor gating deficits could be an aspect of the co-morbidity between FASD and mental health conditions.

Hippocampal neuron populations are reduced in vervet monkeys with fetal alcohol exposure

“…Second, because the volume of Ammon's horn did not expand normally in FAE animals, by 2 years of age, the hippocampus of the FAE subjects was significantly smaller than that of the controls. Conspecifics exposed to similar quantities of ethanol prenatally display alterations of social behavior and deficits in acquiring cognitive tasks (Palmour et al, unpublished) and rhesus macaques exposed to somewhat lower concentrations of ethanol during gestation exhibit elevated acoustic startle responses and reduced habituation to stress (Schneider, Moore, & Kraemer, 2004; Schneider et al, 2013, 2008). …”

Changes in the α4β2* nicotinic acetylcholine system during chronic controlled alcohol exposure in nonhuman primates

“…The protocol of alcohol administration is a major strength of the present work, as it provides tightly controlled administration of alcohol to alcohol naïve subjects of the same age, rearing conditions, and history of alcohol exposure (Vivian et al, 2001; Schneider et al, 2013), however, the different prenatal conditions may have introduced variability into the data. Individual variations in alcohol distribution and metabolism could have resulted in different cerebral alcohol concentrations despite identical administered doses, potentially limiting this study.…”

“…These experiments examined eight adult rhesus monkeys ( Macaca mulatta; 4M, 4F; 19.6–19.8 yr; 7.5–15.3 kg). All subjects were members of a cohort exposed to prenatal alcohol and/or prenatal stress and were reared under otherwise identical conditions (Schneider et al, 2013). A first [ 18 F]nifene PET scan (‘baseline’ scan) was conducted while subjects were alcohol-naïve.…”

Studying longitudinal trajectories in animal models of psychiatric illness and their translation to the human condition

“…Because interaction with the mother, nursing, and alcohol exposure are all factors that could recruit the reward system, it is not surprising that alcohol preference persists among these offspring (Pepino et al, 2004; Ponce et al, 2011; Pueta et al, 2008). Studies in rhesus macaques show that prenatal exposures to alcohol result in persistent differences in pre-pulse inhibition (Schneider et al, 2013), and other studies show interactive effects of stress and alcohol, such that offspring show alterations in dopamine-system function, HPA-axis activity, and exhibit a sensory processing disorder-like phenotype, all of which are observed among individuals with autism spectrum disorders, ASD (Converse et al, 2013; Schneider et al, 2004, 2008). Since alcohol preference and stress reactivity are traits that are heritable, it may be that genetic vulnerability factors could interact with pre-and post-natal ethanol exposure to predict future vulnerabilities.…”