Acute Ethanol Inhibition of Adult Hippocampal Neurogenesis Involves <scp>CB</scp>1 Cannabinoid Receptor Signaling

Khatri, Dal; Laroche, Geneviève; Grant, Marion L.; Jones, Victoria; Vetreno, Ryan P.; Crews, Fulton T.; Mukhopadhyay, Somnath

doi:10.1111/acer.13608

Cited by 15 publications

(9 citation statements)

References 52 publications

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“…Previous studies have also found that AIE exposure causes a persistent increase in hippocampal expression of proinflammatory Toll-like receptors (TLR), the proinflammatory cytokine TNF-α and high mobility group box 1 (HMGB1), as well as the transcriptionally active subunit phosphorylated (activated) NFκB (pNFκB p65) common to proinflammatory signaling 52,53 . The persistence of neuroimmune signaling after AIE may be related to the persistent increases in adult hippocampal HMGB1, which can activate TLR and the receptor for advanced glycation end-products (RAGE).…”

Section: Resultsmentioning

confidence: 99%

Changes in Neuroimmune and Neuronal Death Markers after Adolescent Alcohol Exposure in Rats are Reversed by Donepezil

Swartzwelder

Healey

et al. 2019

Sci Rep

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Adolescent intermittent ethanol (AIE) exposure diminishes neurogenesis and dendritic spine density in the dentate gyrus. The cholinesterase inhibitor, donepezil (Aricept), reverses AIE effects on dendritic spines, possibly by interacting with inflammatory and/or epigenetic mediators after AIE exposure. This study tests the hypothesis that donepezil reverses AIE-induced neuroimmune, and epigenetic changes in the adult dentate gyrus. Adolescent Sprague-Dawley male rats (PD30-43) were given 10 intermittent, intragastric doses of ethanol (5.0 g/kg) or isovolumetric water (AIW). Twenty-one days later half of the animals from each group were treated with either donepezil or isovolumetric water (i.g.) once daily for four days. Two hours after the last donepezil or water dose animals were sacrificed and brains prepared for immunohistochemical analyses. AIE reduced immunoreactivity for doublecortin (DCX) and increased immunoreactivity for activated caspase-3 and death receptor-3 in adulthood, suggesting an enduring attenuation of neurogenesis and an increase in progenitor death. These effects were reversed by donepezil treatment in adulthood. AIE also increased immunoreactivity for the inflammatory signaling molecules HMGB1 and RAGE, as well as the activated phosphorylated transcription factor pNFκB p65, and the gene silencing marker dimethylated histone H3K9. All of these AIE effects were also reversed by donepezil, with the exception of HMGB1.

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Section: Resultsmentioning

confidence: 99%

Changes in Neuroimmune and Neuronal Death Markers after Adolescent Alcohol Exposure in Rats are Reversed by Donepezil

Swartzwelder

Healey

et al. 2019

Sci Rep

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“…In establishing novel rodent models of THC and alcohol co-use, we found that injected or orally administered THC can dose-dependently interact with alcohol to differently influence feeding behaviors. Importantly, our established method of voluntary THC and alcohol ingestion is an improvement over two recent involuntary coadministration models (Khatri et al 2018;Swartzwelder et al 2012), and closely recapitulates the manner of human consumption. Our methods can be easily adapted for investigations of the behavioral, metabolic, and neurobiological mechanisms of joint alcohol and cannabinoid use in adolescent and adult subjects.…”

Section: Resultsmentioning

confidence: 99%

Combined ∆9-tetrahydrocannabinol and moderate alcohol administration: effects on ingestive behaviors in adolescent male rats

et al. 2018

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Rationale-Whereas co-use of alcohol and marijuana is prevalent in adolescents, the effects of such drug co-exposure on ingestive and cognitive behaviors remain largely unexplored. We hypothesized that co-exposure to alcohol and Δ 9-tetrahydrocannabinol (THC), the main psychoactive constitute of marijuana, alters feeding behavior and cognition differently from either drug alone. Methods-Male rats received daily THC (3-20 mg/kg/day) or oil vehicle through subcutaneous injection or consumption of a cookie with access to saccharin or saccharin-sweetened alcohol during adolescence (P30-45). Barnes maze and sucrose preference tests were applied to assess spatial memory and behavioral flexibility and abstinence-related anhedonia, respectively. Results-Subcutaneous THC did not affect alcohol intake, but dose-dependently increased acute (3-h) chow intake and reduced weight gain. Moderate alcohol consumption reduced the acute hyperphagic effect of subcutaneous THC. By contrast, oral THC at a dose > 5 mg/kg robustly reduced alcohol intake without affecting 3-h chow intake. At this dose, some rats stopped consuming the THC-laced cookies. Furthermore, oral THC reduced weight gain, and co-exposure to alcohol alleviated this effect. Chronic subcutaneous, but not oral, THC reduced sucrose intake during abstinence. Neither treatment impaired cognitive behaviors in the Barnes maze. Conclusion-Moderate alcohol and THC consumption can interact to elicit unique outcomes on ingestive behaviors and energy balance. Importantly, this study established a novel model of voluntary alcohol and THC consumption for studying mechanisms underlying the consequences of adolescent onset co-use of the two drugs.

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“…Chronic alcohol exposure is known to inhibit adult hippocampal neurogenesis, and in this Virtual Issue, Khatri and colleagues used a rat binge‐drinking model to show that acute alcohol inhibition of neurogenesis depends on activation of CB1 receptors and is exacerbated by further activation of these receptors (Khatri et al., ). This model suggests that acute activation of endocannabinoid signaling by alcohol is an important step in impairment of hippocampal neurogenesis.…”

Section: Endocannabinoids Exocannabinoids and Alcohol Actionsmentioning

confidence: 99%

Cannabis and Alcohol: From Basic Science to Public Policy

Chung

Harris

2019

Alcoholism Clin & Exp Res

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Acute Ethanol Inhibition of Adult Hippocampal Neurogenesis Involves CB1 Cannabinoid Receptor Signaling

Abstract: Together, these findings suggest that acute CB1R cannabinoid receptor activation and binge EtOH treatment reduce neurogenesis through mechanisms involving CB1R.

Cited by 15 publications

References 52 publications

Changes in Neuroimmune and Neuronal Death Markers after Adolescent Alcohol Exposure in Rats are Reversed by Donepezil

Changes in Neuroimmune and Neuronal Death Markers after Adolescent Alcohol Exposure in Rats are Reversed by Donepezil

Combined ∆9-tetrahydrocannabinol and moderate alcohol administration: effects on ingestive behaviors in adolescent male rats

Cannabis and Alcohol: From Basic Science to Public Policy

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