Increased Maternal Care Rescues Altered Reinstatement Responding Following Moderate Prenatal Alcohol Exposure

Abstract

Background: Fetal alcohol spectrum disorders (FASD) commonly include deficits in learning, memory, and executive control that can have a severe negative impact on quality of life across the life span. It is still unclear how prenatal alcohol exposure (PAE) affects executive control processes, such as control over reward seeking, that lead to inappropriate behavior later in life. Learning and reinstatement of a previously learned response after extinction is a simple, well-validated measure of both acquisition of a rewarded instrumental response and sensitivity to reward and reward-associated cues. We investigated the effects of PAE on learning, extinction, and reinstatement of a simple instrumental response for food reward. Next, we assessed the effectiveness of an early intervention, communal nest (CN) housing, on increased reinstatement of an extinguished response seen after PAE.Methods: To assess the effects of PAE on control over reward seeking, we tested male and female PAE and saccharine (SAC) controls raised in a standard nest (SN) on the acquisition, extinction, and food reward-induced reinstatement of an instrumental response utilizing a touch screen-based paradigm. Next, in order to examine the effects of an early-life intervention on these behaviors, we tested PAE and SAC mice raised in a CN early-life environment on these behaviors.Results: PAE mice readily acquired and extinguished a simple touch response to a white square stimulus. However, PAE mice showed significantly increased and persistent reinstatement compared to controls. Increased maternal care via rearing in CN slowed acquisition and sped extinction learning and rescued the significantly increased reinstatement responding in PAE mice.Conclusions: Together these results demonstrate that even moderate PAE is sufficient to alter control over reward seeking as measured by reinstatement. Importantly, an early-life intervention previously shown to improve cognitive outcomes in PAE mice was sufficient to ameliorate this effect.

Moderate prenatal alcohol exposure impairs cognitive control, but not attention, on a rodent touchscreen continuous performance task

“…Studies using exposure models in mice and rats similar to those used in the current study further support this conclusion as studies utilizing the New Mexico Alcohol Research Center model have shown that this exposure generally spares learning processes including acquisition of instrumental responding, extinction of learned associations, visual discrimination and acquisition of spatial responses. In contrast, these exposures impair performance when task demands are increased either via reinstatement of reward after extinction or reversal of a learned visual or spatial discrimination 24,39,48 . Rat studies using this model that yield similar BAC (~80 mg/dL) also generally spare learning yet impair performance when contingencies are changed or reversed 49–51 .…”

“…Females continued to consume alcohol or saccharin solutions throughout the 5‐day mating period. Pregnancy was positively determined by monitoring weight gain every 3 to 4 days to minimize handling stress as previously described 23,24,37,39 . Access to alcohol was withdrawn beginning on postnatal day 0 using a step‐down procedure over a 6‐day period and offspring were weaned at approximately 23 days of age.…”

“…All operant behavior was conducted in a chamber measuring 21.6 × 17.8 × 12.7 cm (model #ENV‐307W, Med Associates, St. Albans, Vermont) housed within a sound‐ and light‐attenuating box (Med Associates, St. Albans, Vermont), as previously described 23,24 . The standard grid floor of the chamber was covered with a solid acrylic plate to facilitate ambulation.…”

“…Models of developmental alcohol exposure in the rodent have particular translational relevance 20 as studies utilizing PAE have been shown to have blood alcohol content (BAC) congruent to those seen during maternal drinking in humans and rodent PAE studies have been able to model deficits seen in persons with FASD across multiple behavioral domains 21 . For example, recent studies have shown that PAE in rodents leads to long‐term deficits in measures of executive control including choice learning, value updating and control over reward seeking across a range of alcohol doses, administration routes and assessment modality 22–26 . While few studies have examined the impact of PAE on attention and response inhibition using CPT measures, developmental alcohol exposure has been shown to impair response inhibition on passive avoidance and taste aversion as well as slow acquisition of auditory go/no go discriminations 27,28 .…”

Corticostriatal deficits underlying cognitive impairments induced by fetal exposure to alcohol

“…Interestingly, other studies reported that maladaptive perseverative responses underlie inflexible behavior upon changes in contextual associations. In fact, in the absence of overt learning deficits, FAE adult mice display enhanced reinstatement of previously extinguished responses (108). These impairments are associated with reversal learning deficits, indicative of altered cognitive flexibility, in both adolescent and adult FAE offspring (43,102,(109)(110)(111).…”