Environmental Enrichment Rescues Endocannabinoid-Dependent Synaptic Plasticity Lost in Young Adult Male Mice after Ethanol Exposure during Adolescence

Abstract

Binge drinking (BD) is a serious health concern in adolescents as high ethanol (EtOH) consumption can have cognitive sequelae later in life. Remarkably, an enriched environment (EE) in adulthood significantly recovers memory in mice after adolescent BD, and the endocannabinoid, 2-arachydonoyl-glycerol (2-AG), rescues synaptic plasticity and memory impaired in adult rodents upon adolescent EtOH intake. However, the mechanisms by which EE improves memory are unknown. We investigated this in adolescent male C57BL/6J mice exposed to a drinking in the dark (DID) procedure four days per week for a duration of 4 weeks. After DID, the mice were nurtured under an EE for 2 weeks and were subjected to the Barnes Maze Test performed the last 5 days of withdrawal. The EE rescued memory and restored the EtOH-disrupted endocannabinoid (eCB)-dependent excitatory long-term depression at the dentate medial perforant path synapses (MPP-LTD). This recovery was dependent on both the cannabinoid CB1 receptor and group I metabotropic glutamate receptors (mGluRs) and required 2-AG. Also, the EE had a positive effect on mice exposed to water through the transient receptor potential vanilloid 1 (TRPV1) and anandamide (AEA)-dependent MPP long-term potentiation (MPP-LTP). Taken together, EE positively impacts different forms of excitatory synaptic plasticity in water- and EtOH-exposed brains.

The effect of omega-3 fatty acids on alcohol-induced damage

“…Binge drinking during adolescence has a long-lasting impact on hippocampal neurogenesis increasing cell death ( 5 , 6 ) as well as on parahippocampal and neocortical structures altering brain plasticity, cognition and behavior ( 7 – 10 ). Likewise, we observed deficits in recognition, spatial and associative memory in early adulthood after chronic ethanol intake during adolescence ( 11 , 12 ). Cognitive impairment in adult brain after adolescent alcohol intake correlates with changes in white matter, disrupted gray matter ( 13 ), reduced hippocampal volume and low levels of brain-derived neurotrophic factor in the adult hippocampus ( 14 , 15 ).…”

Environmental enrichment alleviates cognitive and psychomotor alterations and increases adult hippocampal neurogenesis in cocaine withdrawn mice

“…In recent years, great progress has been made in investigating the influence of environmental conditions on the development of drug abuse and addiction. 29 Although recent data show that an enriched environment recovers cognitive deficits and improves synaptic plasticity in mice abstinent from ethanol, 34 Regarding exploratory activity, cocaine groups showed hyperlocomotion when exploring novel environments such as the OF and the Y maze tasks, as reported in our previous work. 10 Such exacerbated motor activation was counteracted by EE.…”

“…In recent years, great progress has been made in investigating the influence of environmental conditions on the development of drug abuse and addiction 29 . Although recent data show that an enriched environment recovers cognitive deficits and improves synaptic plasticity in mice abstinent from ethanol, 34 little is known about the effect of EE on cognitive impairment due to cocaine. The present study provided environmental stimulation after discontinuation of chronic cocaine administration.…”

Omega-3 Recovers Cannabinoid 1 Receptor Expression in the Adult Mouse Brain after Adolescent Binge Drinking

“…Interestingly, young adult mice under enriched environment recovered motor coordination and balance after adolescent binge drinking [45]. It is likely that the ECS participates in this motor improvement, as it is the case in the memory recovery elicited by environmental enrichment via the restoration of endocannabinoid-dependent excitatory synaptic plasticity, in which CB 1 receptors, group I metabotropic glutamate receptors and 2-AG were involved [9].…”

“…Binge drinking during adolescence has a long-lasting impact on cognition and behavior via interference with brain neurochemical systems, including the ECS which participates in the regulation of motivation and EtOH intake [6][7][8][9]. EtOH exposure alters both CB 1 mRNA and protein [10,11], changing the availability and binding of the receptor [12,13].…”