Early-life ketamine exposure attenuates the preference for ethanol in adolescent Sprague-Dawley rats

Franco, Daniela; Zamudio, Jennifer; Blevins, Kennedy M.; Núñez-Larios, Eric A.; Ricoy, Ulises M.; Iñiguez, Sergio D.; Zavala, Arturo R.

doi:10.1016/j.bbr.2020.112626

Cited by 11 publications

(3 citation statements)

References 49 publications

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“…While few studies have previously investigated the effects of early ketamine exposures on reward behavior 41 – 43 , the present study differs in several important aspects. The first important difference is the dose and duration of ketamine treatment.…”

Section: Discussionmentioning

confidence: 99%

Repeated ketamine anesthesia during neurodevelopment upregulates hippocampal activity and enhances drug reward in male mice

Cui

Lee

et al. 2022

Commun Biol

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Early exposures to anesthetics can cause long-lasting changes in excitatory/inhibitory synaptic transmission (E/I imbalance), an important mechanism for neurodevelopmental disorders. Since E/I imbalance is also involved with addiction, we further investigated possible changes in addiction-related behaviors after multiple ketamine anesthesia in late postnatal mice. Postnatal day (PND) 16 mice received multiple ketamine anesthesia (35 mg kg−1, 5 days), and behavioral changes were evaluated at PND28 and PND56. Although mice exposed to early anesthesia displayed normal behavioral sensitization, we found significant increases in conditioned place preference to both low-dose ketamine (20 mg kg−1) and nicotine (0.5 mg kg−1). By performing transcriptome analysis and whole-cell recordings in the hippocampus, a brain region involved with CPP, we also discovered enhanced neuronal excitability and E/I imbalance in CA1 pyramidal neurons. Interestingly, these changes were not found in female mice. Our results suggest that repeated ketamine anesthesia during neurodevelopment may influence drug reward behavior later in life.

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Section: Discussionmentioning

confidence: 99%

Repeated ketamine anesthesia during neurodevelopment upregulates hippocampal activity and enhances drug reward in male mice

Cui

Lee

et al. 2022

Commun Biol

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“…Contrarily, other studies found a greater sensitivity for ketamine in male rodents, for example, while ketamine decreased ethanol consumption in male rats that self-administered high levels of ethanol, it increased ethanol consumption in female rats that showed low levels of ethanol self-administration [73]. Also, adolescent exposure to ketamine signi cantly decreased preference for ethanol consumption in males, with a smaller reduction of ethanol consumption in females [74]. In general, prior results with ketamine at the preclinical and clinical level proved some bene cial effects on ameliorating ethanol-motivated behaviors for both sexes (see recent reviews by [32][33][34][35]), although with some differences in between sexes that should be further studied since they will likely play an important role in the future development of therapeutical options for alcohol use disorders.…”

Section: Discussionmentioning

confidence: 89%

Cannabidiol or ketamine for preventing the impact of adolescent early drug initiation on voluntary ethanol consumption in adulthood

Garcia-Fuster,

Colom-Rocha,

Bis-Humbert

2024

Preprint

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Few studies have previously evaluated the long-term impact of initiating the combined use of alcohol and cocaine early-in-life during adolescence. Our preclinical study characterized changes in affective-like behavior and/or voluntary ethanol consumption emerging later on in adulthood during withdrawal and induced by adolescent drug exposure, as well as tested therapeutical interventions (i.e., cannabidiol or ketamine) to prevent the observed effects. We performed 3 independent studies with male and female Sprague-Dawley rats, treated in adolescence (postnatal days, PND 29–38) with ethanol, cocaine, their combination or vehicle. Following prolonged forced-withdrawal, adult rats were (1) scored for their affective-like state (forced-swim, elevated-plus maze, novelty-suppressed feeding, sucrose preference), (2) allowed to freely drink ethanol for 6 weeks (two-bottle choice), or (3) treated with cannabidiol or ketamine before given access to ethanol in adulthood. The results proved no signs of increased negative affect during withdrawal in adulthood following the adolescent treatments. However, adolescent ethanol exposure was a risk-factor for later developing an increased voluntary ethanol consumption in adulthood, both for male and female rats. This risk was similar when ethanol was combined with adolescent cocaine exposure, since cocaine alone showed no effects on later ethanol intake. Finally, rats exposed to adolescent ethanol and pretreated during forced-withdrawal with cannabidiol (and/or ketamine, but just for females) reduced ethanol voluntary consumption in adulthood. Our data provided two therapeutical options capable of preventing the impact of an early drug initiation during adolescence by decreasing voluntary ethanol consumption in adult rats.

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“…This leads to a reduction of glutamate neurotransmission and further supports the concept of ethanol acting as a non-competitive NMDAR antagonist. 68 Although the nature of mammalian ion channel functionality in response to ethanol exposure is inconclusive; there is viable proof showing the linear relationship of NMDA depressed activity due to intoxicating levels of ethanol.…”

Section: Introductionmentioning

confidence: 99%

Potential Link Between Exercise and N-Methyl-D-Aspartate Glutamate Receptors in Alcohol Use Disorder: Implications for Therapeutic Strategies

Sedhom,

Hammond,

Thanos

et al. 2024

PRBM

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Early-life ketamine exposure attenuates the preference for ethanol in adolescent Sprague-Dawley rats

Cited by 11 publications

References 49 publications

Repeated ketamine anesthesia during neurodevelopment upregulates hippocampal activity and enhances drug reward in male mice

Repeated ketamine anesthesia during neurodevelopment upregulates hippocampal activity and enhances drug reward in male mice

Cannabidiol or ketamine for preventing the impact of adolescent early drug initiation on voluntary ethanol consumption in adulthood

Potential Link Between Exercise and N-Methyl-D-Aspartate Glutamate Receptors in Alcohol Use Disorder: Implications for Therapeutic Strategies

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