Theoretical Frameworks and Mechanistic Aspects of Alcohol Addiction: Alcohol Addiction as a Reward Deficit/Stress Surfeit Disorder

Koob, George F.; Vendruscolo, Leandro F.

doi:10.1007/7854_2023_424

Cited by 10 publications

(17 citation statements)

References 351 publications

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“…Those studies support our findings that 3α,5α-THP is thought to alter EtOH self-administration by acting as a positive allosteric modulator of GABA A receptors (Puia et al, 1990(Puia et al, , 1993, although it selectively enhances tonic currents mediated by extrasynaptic GABA A receptors containing the δ subunit (Belelli & Lambert, 2005;Carver & Reddy, 2013). Alcohol is known to enhance inhibitory tone onto GABAergic neurons, producing a subsequent disinhibition that can lead to impairments in behavioral control of alcohol seeking and intake (Koob, 2013). However, a growing body of evidence has shown that 3α,5α-THP can increase GABA A receptormediated inhibition, offset alcohol-induced disinhibition, and potentially protect against increases in alcohol consumption (see review (Domi et al, 2021)).…”

Section: Intra-acbc Infusion Of 3α 5α-thp Reduces Operant Alcohol Sel...mentioning

confidence: 99%

Pharmacological administration of 3α,5α‐THP into the nucleus accumbens core increases 3α,5α‐THP expression and reduces alcohol self‐administration

Ornelas

Boero

Voorhies

et al. 2023

Alcohol: Clinical and Experimental Research

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Background: Alcohol affects multiple circuits in the brain, mainly disrupting the delicate balance between inhibitory γ-aminobutyric acid (GABA) transmission and excitatory glutamate signaling in brain areas involved in reward circuits. These include the amygdala, nucleus accumbens (Acb), and ventral tegmental area (VTA). This action impairs circuits that regulate behavioral control of craving and alcohol seeking and intake. Studies in both rodent models and postmortem human brain of patients with alcohol use disorder (AUD) have highlighted the association between the loss of GABAergic inhibition and the development of addiction. The neurosteroid (3α,5α)-3hydroxypregnan-20-one (3α,5α-THP) is a potent positive modulator of GABA A receptors. Chronic alcohol consumption reduces 3α,5α-THP levels, resulting in decreased GABA inhibition. We previously demonstrated that enhancing neurosteroid biosynthesis by overexpression of the cholesterol side-chain cleavage enzyme P450scc decreased alcohol intake in male alcohol-preferring rats (P-rats). While most of the evidence of alcohol-induced alterations comes from studies in male subjects, some data show that females are more vulnerable to alcohol's effects than males. Methods:In this study, we investigated the ability of 3α,5α-THP direct infusions in two brain regions that contribute to alcohol reinforcement, the VTA and Acb core (AcbC), to regulate alcohol self-administration in female P-rats.Results: Administration of 3α,5α-THP into the AcbC increased 3α,5α-THP-positive cell expression in this area and reduced alcohol self-administration. By contrast, 3α,5α-THP infusion into the VTA did not significantly affect alcohol self-administration, though trends for a reduction were found. Conclusions:Our results show that local increases in 3α,5α-THP in the AcbC may alter mesolimbic activity that drives a reduction in alcohol self-administration.

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Section: Intra-acbc Infusion Of 3α 5α-thp Reduces Operant Alcohol Sel...mentioning

confidence: 99%

Pharmacological administration of 3α,5α‐THP into the nucleus accumbens core increases 3α,5α‐THP expression and reduces alcohol self‐administration

Ornelas

Boero

Voorhies

et al. 2023

Alcohol: Clinical and Experimental Research

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“…While there is a substantial literature on risk factors for alcohol use and binge drinking (e.g., Cooper et al, 2016; Votaw & Witkiewitz, 2021), existing studies tend to assume the same risk factors are relevant for all individuals who drink, regardless of their level of alcohol use problems or the presence of AUD. In contrast, the multistage model of drug addiction posits that alcohol use risk processes change as individuals progress from non‐disordered drinking to alcohol use disorders (Koob, 2013; Koob & Volkow, 2010). This theory has been tested predominately in animal and neuropsychological studies (Koob, 2013, Koob & Volkow, 2010), with little research examining whether risk processes for alcohol use differ depending on an individual's level of AUD symptom severity outside of the lab (for an exception see Cho et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, the multistage model of drug addiction posits that alcohol use risk processes change as individuals progress from non‐disordered drinking to alcohol use disorders (Koob, 2013; Koob & Volkow, 2010). This theory has been tested predominately in animal and neuropsychological studies (Koob, 2013, Koob & Volkow, 2010), with little research examining whether risk processes for alcohol use differ depending on an individual's level of AUD symptom severity outside of the lab (for an exception see Cho et al, 2019). However, this model has potential to elucidate individual‐level differences in daily risk processes for alcohol use.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…The multistage model of drug addiction posits that risk factors for alcohol use change as individuals transition from infrequent non‐disordered drinking (i.e., binge/intoxication stage) to an AUD (withdrawal/negative affect stage; Koob, 2013; Koob & Volkow, 2010). When drinking is infrequent and AUD is not present (i.e., binge/intoxication stage), drinking is theorized to be driven by positive reinforcement (i.e., increasing a desired state), such as drinking to make a social gathering more fun or to make one feel more sociable (Koob, 2013, Koob & Volkow, 2010). Based on this, we would expect that positive affect and positive reinforcement expectancies (e.g., the expectation that alcohol will increase one's sociability) and evaluations (e.g., the desirability of these sociability effects of alcohol) would be predictors of alcohol use among individuals without AUD.…”

Section: Introductionmentioning

confidence: 99%

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Event‐level positive and negative reinforcement risk factors for alcohol use: Moderation by individual‐level alcohol consequences and post‐traumatic stress disorder symptom severity

Dyar,

Kaysen

2023

Alcohol: Clinical and Experimental Research

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BackgroundThe multistage model of drug addiction posits that risk processes contributing to alcohol use change as individuals develop alcohol use disorders. However, few studies have tested this theory outside of the lab or at the event level. We assessed whether event‐level associations between positive reinforcement (e.g., positive affect, sociability expectancies) and negative reinforcement risk factors (e.g., negative affect, tension reduction expectancies) and same‐/next‐day alcohol consumption varied as a function of an individual's level of alcohol consequences. Given elevated alcohol use consequences among individuals with post‐traumatic stress disorder (PTSD) and disruptions in reward processing that affect this population, we also tested whether these processes differed based on the presence and severity of PTSD.MethodsWe used data from a 30‐day ecological momentary assessment study with 174 undergraduate women who regularly engaged in heavy episodic drinking. A majority (78%) of the sample had experienced sexual assault and 44% had current PTSD. Analyses used Bayesian multilevel structural equation modeling with diffuse (non‐informative) priors. We used markov chain monte carlo (MCMC) algorithms to generate a series of 10,000 random draws from the multivariate posterior distribution of our sample for each model.ResultsResults partially supported the multistage model. Event‐level negative reinforcement risk factors only predicted more alcohol consumption among individuals who experienced more alcohol consequences. Findings for positive reinforcement risk factors were partially consistent with hypotheses. Overall, findings appear to operate similarly across PTSD symptom severity.ConclusionsResults suggest that interventions for heavy episodic drinking could benefit from attending to an individual's level of alcohol consequences. For example, preventive interventions for individuals who tend to experience few consequences may benefit more from addressing positive reinforcement risk factors, while treatment interventions for those who experience more consequences may benefit from attending to both positive and negative reinforcement.

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Reducing the harms of alcohol: nutritional interventions and functional alcohol alternatives

Belelli,

Riva,

Nutt

2024

International Review of Neurobiology

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Theoretical Frameworks and Mechanistic Aspects of Alcohol Addiction: Alcohol Addiction as a Reward Deficit/Stress Surfeit Disorder

Cited by 10 publications

References 351 publications

Pharmacological administration of 3α,5α‐THP into the nucleus accumbens core increases 3α,5α‐THP expression and reduces alcohol self‐administration

Pharmacological administration of 3α,5α‐THP into the nucleus accumbens core increases 3α,5α‐THP expression and reduces alcohol self‐administration

Event‐level positive and negative reinforcement risk factors for alcohol use: Moderation by individual‐level alcohol consequences and post‐traumatic stress disorder symptom severity

Reducing the harms of alcohol: nutritional interventions and functional alcohol alternatives

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