Alcohol-Endocannabinoid Interactions: Implications for Addiction-Related Behavioral Processes

Serrano, Antonia; Natividad, Luis A.

doi:10.35946/arcr.v42.1.09

Cited by 8 publications

(2 citation statements)

References 207 publications

(229 reference statements)

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“…Additionally, the eCB system has been implicated in the development of habitual behaviors, as well as the voluntary taking of ethanol [ 12 , 72 , 73 ]. It was previously unclear whether ethanol can induce differential eCB responses involved in different ethanol-related behaviors.…”

Section: Discussionmentioning

confidence: 99%

Striatonigral direct pathway 2-arachidonoylglycerol contributes to ethanol effects on synaptic transmission and behavior

Augustin,

Gracias,

Luo

et al. 2023

Neuropsychopharmacol.

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Endocannabinoids (eCB) and cannabinoid receptor 1 (CB1) play important roles in mediating short- and long-term synaptic plasticity in many brain regions involved in learning and memory, as well as the reinforcing effects of misused substances. Ethanol-induced plasticity and neuroadaptations predominantly occur in striatal direct pathway projecting medium spiny neurons (dMSNs). It is hypothesized that alterations in eCB neuromodulation may be involved. Recent work has implicated a role of eCB 2-arachidonoylglycerol (2-AG) in the rewarding effects of ethanol. However, there is insufficient research to answer which cellular subtype is responsible for mediating the 2-AG eCB signal that might be involved in the rewarding properties of ethanol and the mechanisms by which that occurs. To examine the role of dMSN mediated 2-AG signaling in ethanol related synaptic transmission and behaviors, we used conditional knockout mice in which the 2-AG-synthesizing enzyme diacylglycerol lipase α (DGLα) was deleted in dMSNs, DGLαD1-Cre+. Using acute brain slice photometry and a genetically encoded fluorescent eCB sensor, GRABeCB2.0, to assess real-time eCB mediated activity of sensorimotor inputs from primary motor cortices (M1/M2) to the dorsolateral striatum, we showed that DGLαD1-Cre+ mice had blunted evoked eCB-mediated presynaptic eCB signaling compared to littermate controls. Furthermore, ethanol induced eCB inhibition was significantly reduced in DGLαD1-Cre+ deficient mice. Additionally, there was a reduction in the duration of loss of righting reflex (LORR) to a high dose of ethanol in the DGLαD1-Cre+ mice compared to controls. These mice also showed a male-specific decrease in ethanol preference accompanied by an increase in ethanol-induced water consumption in a voluntary drinking paradigm. There were no significant differences observed in sucrose and quinine consumption between the genotypes. These findings reveal a novel role for dMSN mediated 2-AG signaling in modulating ethanol effects on presynaptic function and behavior.

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Section: Discussionmentioning

confidence: 99%

Striatonigral direct pathway 2-arachidonoylglycerol contributes to ethanol effects on synaptic transmission and behavior

Augustin,

Gracias,

Luo

et al. 2023

Neuropsychopharmacol.

View full text Add to dashboard Cite

show abstract

“…From synapse to policy, the reviews in this series reflect the current state of the science on the reciprocal impact of alcohol and cannabinoids on an individual and the society at large. Several comprehensive reviews summarize findings from preclinical and human studies on the effects of alcohol exposure on the eCB system as a whole 28 and more specifically at the synaptic level in the brain. 29 In their review of the mechanisms of cannabinoid receptor signaling in hepatic pathogenesis, Yang, Choi, and Jeong summarize evidence in support of cannabinoid-based treatments for alcohol-associated liver disease.…”

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confidence: 99%