Environmental Enrichment During Adolescence Mitigates Cognitive Deficits and Alcohol Vulnerability due to Continuous and Intermittent Perinatal Alcohol Exposure in Adult Rats

Abstract

Perinatal alcohol exposure affects ontogenic neurodevelopment, causing physical and functional long-term abnormalities with limited treatment options. This study investigated long-term consequences of continuous and intermittent maternal alcohol drinking on behavioral readouts of cognitive function and alcohol vulnerability in the offspring. The effects of environmental enrichment (EE) during adolescence were also evaluated. Female rats underwent continuous alcohol drinking (CAD)-or intermittent alcohol drinking paradigm (IAD), along pregestation, gestation, and lactation periods-equivalent to the whole gestational period in humans. Male offspring were reared in standard conditions or EE until adulthood and were then assessed for declarative memory in the novel object recognition test; spatial learning, cognitive flexibility, and reference memory in the Morris water maze (MWM); alcohol consumption and relapse by a two-bottle choice paradigm. Our data show that perinatal CAD decreased locomotor activity, exploratory behavior, and declarative memory with respect to controls, whereas perinatal IAD displayed impaired declarative memory and spatial learning and memory. Moreover, both perinatal alcohol-exposed offspring showed higher vulnerability to alcohol consummatory behavior than controls, albeit perinatal IAD rats showed a greater alcohol consumption and relapse behavior with respect to perinatal-CAD progeny. EE ameliorated declarative memory in perinatal CAD, while it mitigated spatial learning and reference memory impairment in perinatal-IAD progeny. In addition, EE decreased vulnerability to alcohol in both control and perinatal alcohol-exposed rats. Maternal alcohol consumption produces drinking pattern-related

Prenatal alcohol and tetrahydrocannabinol exposure: Effects on spatial and working memory

“…Surprisingly, our findings showed that ethanol exposure during gestation did not produce deficits in spatial learning and memory, in contrast to other preclinical studies using prenatal models ( Patten et al, 2014 ; Brancato et al, 2020 ; Aglawe et al, 2021 ; Mahdinia et al, 2021 ) and 3rd trimester equivalent models ( Thomas et al, 2007 ; Ryan et al, 2008 ; Breit et al, 2019b ). Variation in outcome may be related to route of administration and/or developmental timing.…”

Environmental Enrichment Protects Against Cognition Deficits Caused by Sepsis-Associated Encephalopathy

“…In addition to revealing the existence of familiar object in the rats' memory [62], the increased preference for novel objects also suggests a close relationship between EE and the desire to access novel stimuli [63]. In this study, we did not set a day of habituation to the testing arena prior to the familiarization phase as some previous studies [64] which may increase the noveltyinduced anxiety and result in the excessive freezing behavior in the test phase.…”

Alcohol consumption’s effects on working memory: Examining familial confounding.

“…Additionally, while a significant association detected in a cotwin control model may support a causal hypothesis, it is also important to consider the influence of unique environmental confounding factors within twin pairs that can lead to spurious associations between worse cognitive test performance and higher levels of drinking (Goldberg et al, 2013; Merikangas & McClair, 2012; Tucker-Drob et al, 2013). Studies in both rodents and humans have found that “enriched environments” (e.g., greater social stimulation) can lead to both improved cognitive outcomes and lower vulnerability to alcohol problems (Brancato et al, 2020; Halperin & Healey, 2011; Kendler et al, 2011; Woo & Leon, 2013). Thus, there could be environmental differences between twins that contribute to this association as well.…”