Topiramate-induced neuromodulation of cortico–mesolimbic dopamine function: A new vista for the treatment of comorbid alcohol and nicotine dependence?
Introduction
Alcohol and nicotine dependence are commonly occurring disorders and, together, represent the most important preventable cause of morbidity and mortality in the United States (Miller & Gold, 1998, Mokdad et al., 2004). At a superficial level, it might appear that the cooccurrence of these disorders is simply a reflection of their high independent prevalence rates in the general population or that these behaviors may be linked by occurring commonly within similar social settings or circumstances. Advances in the neurosciences have, however, shown that there are important neurochemical pharmacodynamic interactions between alcohol and nicotine that might summate to increase codependency on both (Littleton & Little, 2002). Furthermore, there is evidence that pharmacokinetic factors associated with the absorption, distribution, and metabolism of both compounds might lead individuals to administer these compounds in such a way that the effects of one of these drugs serve to modulate the effects of the other (Blomqvist et al., 2002, Seaton & Vesell, 1993). Emerging genetic evidence also shows that an earlier onset of smoking is associated with greater likelihood of problem drinking, and fetal exposure to alcohol may increase susceptibility to smoking (Lê, 2002, Prendergast et al., 2002). Nevertheless, despite this striking evidence for substantial neurochemical and biological overlap between alcohol and nicotine dependence, few clinical trials have addressed the possibility of using a common pharmacological approach to treat both disorders simultaneously.
This overview aims to show the epidemiological relationship between alcohol and nicotine dependence, to demonstrate how the neuropharmacological effects of both drugs are associated with their habit-forming properties, and to provide a framework for a common pharmacological approach using the anticonvulsant, topiramate; it concludes by summarizing the results of a recent clinical trial that examined the effects of topiramate on both alcohol and smoking behavior among dependent individuals.
Section snippets
Epidemiology
Previous studies assessing the relationship between alcohol dependence and smoking have suggested a strong connection between the two. In sample sizes ranging from 103 to 1010, surveys of both inpatient and outpatient treatment participants for alcohol dependence showed an 86–97% smoking rate among males and an 82–92% rate among females (Ayers et al., 1976, Bien & Burge, 1990, Burling et al., 1989, Burling & Ziff, 1988, Dreher & Fraser, 1967, Kozlowski et al., 1986, Walton, 1972). Recently,
Neurochemical interactions between alcohol and nicotine
Important neurochemical interactions exist between alcohol and nicotine that can serve to increase the reinforcing effects and, therefore, abuse liability of the combination.
The reinforcing effects of both nicotine and alcohol are mediated through cortico–mesolimbic dopamine pathways (Hemby, 2003, Hemby et al., 1997, Wise & Bozarth, 1987). While the primary action by which alcohol exerts its reinforcing effects is through the disinhibition of the inhibitory effects of γ-amino-butyric acid-A
General mechanisms of action
Topiramate is a novel anticonvulsant that is approved by the Food and Drug Administration for the treatment of childhood epilepsy. However, it is currently under intense investigation as a treatment for a wide range of neuropsychiatric disorders, including alcohol, nicotine, and drug dependence. Topiramate is a sulfamate-substituted analog of fructose-1,6-diphosphate. Its chemical nomenclature is 2,3:4,5-Di-o-isopropylidene-β-d-fructopyranose sulfamate (Fig. 1). From Fig. 1, it can also be seen
Summary
Alcohol and nicotine dependence are commonly occurring disorders that together represent the most important preventable causes of morbidity and mortality in the United States (Miller & Gold, 1998, Mokdad et al., 2004). While there have been differences of opinion as to which disorder to treat first when they occur, there is growing evidence that a management strategy addressing both conditions contemporaneously would be optimal.
Advances in the neurosciences have demonstrated not only that the
Acknowledgments
I thank the National Institute on Alcohol Abuse and Alcoholism for its support through grants AA 10522-08, 12964-01, and 14628-01; the National Institute on Drug Abuse for its support through grant DA 12191-05; the staff at the South Texas Addiction Research and Technology (START) Center, and Robert H. Cormier, Jr. for his assistance with manuscript preparation.
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Aripiprazole and topiramate, alone or in combination, block the expression of ethanol-induced conditioned place preference in mice
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2020, Drug and Alcohol DependenceCitation Excerpt :This outcome may have been expected in regards to topiramate, which has been shown to improve other substance use, including alcohol (Johnson et al., 2003, 2007) and methamphetamine (Ma et al., 2013), and other disorders with dysfunctional impulse control, like binge eating disorder (Claudino et al., 2007; McElroy et al., 2007) and gambling (de Brito et al., 2017). The proposed mechanism being indirect modulation of dopamine within the cortico-mesolimbic system through its more direct effects on GABA and glutamate (Johnson, 2004). In clinical practice, clinicians may have concerns about amphetamines worsening impulsive behavior due to its more direct actions on dopamine.
Role of the treatment environment in the effects of aripiprazole on ethanol-induced behavioral sensitization and conditioned place preference in female mice
2020, Drug and Alcohol DependenceCitation Excerpt :Ethanol exerts its abuse-related behavioral effects by inhibiting the activity of GABAergic interneurons present in VTA, disinhibiting VTA dopamine neurons that project to the nucleus accumbens (Morikawa and Morrisett, 2010). Increased dopamine neurotransmission within the mesolimbic system has been proposed as the main mechanism underlying the rewarding (Diana et al., 2003; Johnson, 2004), reinforcing (Gonzales et al., 2004) and behavioral stimulant effects of ethanol (Nutt, 2014). Aripiprazole is a third-generation neuroleptic drug that acts as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors, as well as an antagonist at 5-HT2A receptors (Burris et al., 2002; Mamo et al., 2007).
Extended release mixed amphetamine salts and topiramate for cocaine dependence: A randomized clinical replication trial with frequent users
2020, Drug and Alcohol DependenceCitation Excerpt :Extended release mixed amphetamine salts (MAS-ER) was found to be more effective than placebo in promoting abstinence in cocaine-dependent adults with ADHD (Levin et al., 2015). Topiramate, an anticonvulsant agent that enhances gamma amino butyric acid (GABA) activity, antagonizes glutamate transmission through effects at AMPA/kainate receptors (Gibbs et al., 2000; Johnson et al., 2013; Skradski and White, 2000), and in turn may reduce midbrain dopaminergic activity (Johnson, 2004; Johnson et al., 2005a) and nicotine-induced dopamine release (Schiffer et al., 2001). Supporting this approach, other GABA-ergic agents have been found to reduce cocaine-induced dopamine release (Dewey et al., 1997).
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2016, Progress in Brain ResearchCitation Excerpt :Topiramate also antagonizes glutaminergic activity through an effect at kainate/alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (Gryder and Rogawski, 2003). Through these processes, topiramate is thought to modulate cortico-mesolimbic dopaminergic activity (Johnson, 2004), potentially stabilizing this activity and subsequently helping to prevent relapse or reduce methamphetamine use. Cognitive-enhancing medications such as modafinil, an analeptic drug with known cognitive-enhancing properties, have garnered recent attention given the known cognitive deficits associated with chronic methamphetamine use (e.g., Ghahremani et al., 2011).