Intermittent ethanol exposure during adolescence impairs cannabinoid type 1 receptor-dependent long-term depression and recognition memory in adult mice

Peñasco, Sara; Rico‐Barrio, Irantzu; Puente, Nagore; Fontaine, Christine J.; Ramos, Almudena; Reguero, Leire; Gerrikagoitia, Inmaculada; Fonseca, Fernando Rodrı́guez de; Suárez, Juan; Barrondo, Sergio; Aretxabala, Xabier; Caño, Gontzal Garcı́a del; Sallés, Joan; Elezgarai, Izaskun; Nahirney, Patrick C.; Christie, Brian R.; Grandes, Pedro

doi:10.1038/s41386-019-0530-5

Cited by 28 publications

(51 citation statements)

References 77 publications

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“…(B) BEC obtained on the last day of EtOH exposure averaged 61.97 ± 2.84 mg/dL ((n = 16) Student's t-test; *** p = 0.0001 vs. control). (C) EtOH intake during each day (g EtOH/kg/2 or 4 h) was measured and (D) total EtOH intake averaged 2.078 ± 0.07 g/kg/h (n = 16), similar to previous studies [5,17,32]. (E) A direct correlation between total EtOH intake and BEC was detected.…”

Section: Did Procedures and Timelinesupporting

confidence: 82%

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

et al. 2021

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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.

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Section: Did Procedures and Timelinesupporting

confidence: 82%

“…The fEPSP area was measured. The magnitude of the CB1-eLTD after LFS was calculated as the percentage between baseline (averaged excitatory responses for 10 min before LFS) and the last 10 min of stable responses 30 min after LFS [17].…”

Section: Slice Preparation and Extracellular Field Recordingsmentioning

confidence: 99%

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

et al. 2021

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“…In this sense, we have recently shown that CB 1 R immunolabeling decreases by 34% in excitatory terminals and the proportion of CB 1 R immunopositive excitatory boutons decreases by 35% in the middle 1/3 ML of the adult mouse subjected to ethanol intake during adolescence (binge drinking model). These deficits in glutamatergic CB 1 Rs were associated with the loss of eCB-eLTD at the MPP-granule cell synapses and an impairment of recognition memory (Peñasco et al, 2020 ). TRPV1 changes upon the loss or absence of CB 1 R remain to be investigated.…”

Section: Discussionmentioning

confidence: 99%

The Absence of the Transient Receptor Potential Vanilloid 1 Directly Impacts on the Expression and Localization of the Endocannabinoid System in the Mouse Hippocampus

et al. 2021

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The transient receptor potential vanilloid 1 (TRPV1) is a non-selective ligand-gated cation channel involved in synaptic transmission, plasticity, and brain pathology. In the hippocampal dentate gyrus, TRPV1 localizes to dendritic spines and dendrites postsynaptic to excitatory synapses in the molecular layer (ML). At these same synapses, the cannabinoid CB1 receptor (CB1R) activated by exogenous and endogenous cannabinoids localizes to the presynaptic terminals. Hence, as both receptors are activated by endogenous anandamide, co-localize, and mediate long-term depression of the excitatory synaptic transmission at the medial perforant path (MPP) excitatory synapses though by different mechanisms, it is plausible that they might be exerting a reciprocal influence from their opposite synaptic sites. In this anatomical scenario, we tested whether the absence of TRPV1 affects the endocannabinoid system. The results obtained using biochemical techniques and immunoelectron microscopy in a mouse with the genetic deletion of TRPV1 show that the expression and localization of components of the endocannabinoid system, included CB1R, change upon the constitutive absence of TRPV1. Thus, the expression of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) drastically increased in TRPV1−/− whole homogenates. Furthermore, CB1R and MAGL decreased and the cannabinoid receptor interacting protein 1a (CRIP1a) increased in TRPV1−/− synaptosomes. Also, CB1R positive excitatory terminals increased, the number of excitatory terminals decreased, and CB1R particles dropped significantly in inhibitory terminals in the dentate ML of TRPV1−/− mice. In the outer 2/3 ML of the TRPV1−/− mutants, the proportion of CB1R particles decreased in dendrites, and increased in excitatory terminals and astrocytes. In the inner 1/3 ML, the proportion of labeling increased in excitatory terminals, neuronal mitochondria, and dendrites. Altogether, these observations indicate the existence of compensatory changes in the endocannabinoid system upon TRPV1 removal, and endorse the importance of the potential functional adaptations derived from the lack of TRPV1 in the mouse brain.

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“…These effects last into adulthood and are associated with loss of CB 1 R in the DGML, reduced CB 1 R‐induced G protein activation and increased expression of MAGL. Furthermore, these long‐term deficits can be rescued by MAGL inhibitors (Penasco et al, 2020).…”

Section: Endocannabinoid Effects On Alcohol Drinking Behaviormentioning

confidence: 99%

Interactions Between Alcohol and the Endocannabinoid System

Kunos

2020

Alcoholism Clin & Exp Res

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Endocannabinoids are lipid mediators that interact with the same cannabinoid receptors that recognize D 9 -tetrahydrocannabinol (THC), the psychoactive constituent of marijuana, to induce similar effects in the brain and periphery. Alcohol and THC are both addictive substances whose acute use elicits rewarding effects that can lead to chronic and compulsive use via engaging similar signaling pathways in the brain. In the liver, both alcohol and endocannabinoids activate lipogenic gene expression leading to fatty liver disease. This review focuses on evidence accumulated over the last 2 decades to indicate that both the addictive neural effects of ethanol and its organ toxic effects in the liver and elsewhere are mediated, to a large extent, by endocannabinoids signaling via cannabinoid-1 receptors (CB 1 R). The therapeutic potential of CB 1 R blockade globally or in peripheral tissues only is also discussed.

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Intermittent ethanol exposure during adolescence impairs cannabinoid type 1 receptor-dependent long-term depression and recognition memory in adult mice

Cited by 28 publications

References 77 publications

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

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

The Absence of the Transient Receptor Potential Vanilloid 1 Directly Impacts on the Expression and Localization of the Endocannabinoid System in the Mouse Hippocampus

Interactions Between Alcohol and the Endocannabinoid System

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