Sex- and hormone-dependent alterations in alcohol withdrawal-induced anxiety and corticolimbic endocannabinoid signaling

Henricks, Angela M.; Berger, Anthony L.; Lugo, Janelle M.; Baxter-Potter, Lydia N.; Bieniasz, Kennedy V.; Petrie, Gavin N; Sticht, Martin A.; Hill, Matthew N.; McLaughlin, Ryan J.

doi:10.1016/j.neuropharm.2017.05.023

Cited by 36 publications

(31 citation statements)

References 75 publications

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“…Interestingly, after acute 1-day withdrawal from 3-week chronic IA alcohol drinking, all four brain regions showed significant increases in the AEA, OEA and PEA, with the NAc and BLA displaying the largest changes (Figure 6). As previous studies showed alterations of AEA levels in the amygdala and other brain regions of rats after chronic alcohol or withdrawal [Rubio et al 2008; Robinson et al 2016; Henricks et al 2017], we further determined dynamic profiles of relative abundances of NAEs in the BLA following chronic IA drinking (no withdrawal) and after one and two weeks of alcohol withdrawal, all of which showed no change compared to control (Figure 7A, S2). Together, this indicates that global NAE dysregulation occurs as a response to acute alcohol withdrawal only.…”

Section: Discussionmentioning

confidence: 99%

Blockade of alcohol escalation and “relapse” drinking by pharmacological FAAH inhibition in male and female C57BL/6J mice

et al. 2017

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Background Anandamide (AEA)-dependent signaling is regulated by the catabolic enzyme fatty acid amide hydrolase (FAAH). Several lines of evidence have demonstrated that FAAH and AEA are involved in the behavioral effects of alcohol. Therefore, we investigated whether a selective FAAH inhibitor, URB597 (Cyclohexylcarbamic acid 3′-[aminocarbonyl]-[1,1′-biphenyl]-3-yl ester), altered alcohol intake in mice in a voluntary alcohol drinking model. Methods Mice, subjected to 3 weeks of chronic intermittent access (IA) in a two-bottle choice paradigm with 24-h access every other day, developed rapid escalation of alcohol intake and high preference. We evaluated the pharmacological effects of URB597 after both acute (1-day) withdrawal from chronic IA and 1-week withdrawal using the alcohol deprivation effect (ADE) model. AEA and N-acyl ethanolamide (NAE) abundances were determined after chronic IA, acute (1-day) or long-term (1 and 2 weeks) withdrawal in four brain regions. Results Acute pretreatment with URB597 reduced alcohol intake and preference after acute withdrawal. This effect was blocked by pretreatment with a selective type 1 cannabinoid receptor (CB1) antagonist, suggesting a CB1-mediated mechanism. Both single- and multiple- dosing regimens with an effective dose of URB597 prevented the ADE, with no tolerance development after the multi-dosing regimen. AEA and NAE levels were transiently increased in all brain regions measured after acute withdrawal, indicating that the endocannabinoid system is involved in acute alcohol withdrawal stress response. Conclusion FAAH inhibitors reduce alcohol escalation and “relapse” drinking in mice.

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Section: Discussionmentioning

confidence: 99%

Blockade of alcohol escalation and “relapse” drinking by pharmacological FAAH inhibition in male and female C57BL/6J mice

et al. 2017

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“…The number of entries and percentage time spent in the open and closed arms, and distance traveled in the open arms of the EPM were compared across groups. The frequency of risk assessment behaviors (i.e., head-dips, stretch-attend postures, and rearing) was also scored manually by trained research assistants blinded to treatment conditions as described previously (Henricks et al, 2017;Berger et al, 2018).…”

Section: Methodsmentioning

confidence: 99%

Vaporized Cannabis Extracts Have Reinforcing Properties and Support Conditioned Drug-Seeking Behavior in Rats

et al. 2020

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Recent trends in cannabis legalization have increased the necessity to better understand the effects of cannabis use. Animal models involving traditional cannabinoid self-administration approaches have been notoriously difficult to establish and differences in the drug used and its route of administration have limited the translational value of preclinical studies. To address this challenge in the field, we have developed a novel method of cannabis self-administration using response-contingent delivery of vaporized ⌬ 9-tetrahydrocannabinol-rich (CAN THC) or cannabidiol-rich (CAN CBD) whole-plant cannabis extracts. Male Sprague-Dawley rats were trained to nose-poke for discrete puffs of CAN THC , CAN CBD , or vehicle (VEH) in daily 1 h sessions. Cannabis vapor reinforcement resulted in strong discrimination between active and inactive operanda. CAN THC maintained higher response rates under fixed ratio schedules and higher break points under progressive ratio schedules compared with CAN CBD or VEH, and the number of vapor deliveries positively correlated with plasma THC concentrations. Moreover, metabolic phenotyping studies revealed alterations in locomotor activity, energy expenditure, and daily food intake that are consistent with effects in human cannabis users. Furthermore, both cannabis regimens produced ecologically relevant brain concentrations of THC and CBD and CAN THC administration decreased hippocampal CB1 receptor binding. Removal of CAN THC reinforcement (but not CAN CBD) resulted in a robust extinction burst and an increase in cue-induced cannabis-seeking behavior relative to VEH. These data indicate that volitional exposure to THC-rich cannabis vapor has bona fide reinforcing properties and collectively support the utility of the vapor self-administration model for the preclinical assessment of volitional cannabis intake and cannabis-seeking behaviors.

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“… 69 , 70 A recent study used this measure to examine sex differences in withdrawal-induced negative affect in rats that were exposed to 6 weeks of intermittent alcohol. 71 The researchers found that male rats increased the frequency of vocalizations during acute withdrawal, whereas female rats did not. 71 A difference in withdrawal sensitivity may incentivize continued heavy alcohol use to a greater degree in males compared to females, thus putting them at a higher risk of AUD.…”

Section: Withdrawal/negative Affect Stagementioning

confidence: 99%

Sex Differences in the Neurobiology of Alcohol Use Disorder

Flores‐Bonilla

Richardson

2020

ARCR

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Sex differences may play a critical role in modulating how chronic or heavy alcohol use impacts the brain to cause the development of alcohol use disorder (AUD). AUD is a multifaceted and complex disorder driven by changes in key neurobiological structures that regulate executive function, memory, and stress. A three-stage framework of addiction (binge/intoxication; withdrawal/negative affect; preoccupation/anticipation) has been useful for conceptualizing the complexities of AUD and other addictions. Initially, alcohol drinking causes short-term effects that involve signaling mediated by several neurotransmitter systems such as dopamine, corticotropin releasing factor, and glutamate. With continued intoxication, alcohol leads to dysfunctional behaviors that are thought to be due in part to alterations of these and other neurotransmitter systems, along with alterations in neural pathways connecting prefrontal and limbic structures. Using the three-stage framework, this review highlights examples of research examining sex differences in drinking and differential modulation of neural systems contributing to the development of AUD. New insights addressing the role of sex differences in AUD are advancing the field forward by uncovering the complex interactions that mediate vulnerability.

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Sex- and hormone-dependent alterations in alcohol withdrawal-induced anxiety and corticolimbic endocannabinoid signaling

Cited by 36 publications

References 75 publications

Blockade of alcohol escalation and “relapse” drinking by pharmacological FAAH inhibition in male and female C57BL/6J mice

Blockade of alcohol escalation and “relapse” drinking by pharmacological FAAH inhibition in male and female C57BL/6J mice

Vaporized Cannabis Extracts Have Reinforcing Properties and Support Conditioned Drug-Seeking Behavior in Rats

Sex Differences in the Neurobiology of Alcohol Use Disorder

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