RESUMO
BACKGROUND: Regular binge drinking is associated with numerous adverse consequences, yet the U.S. Food and Drug Administration (FDA) has approved only 4 medications for the treatment of alcohol use disorders, and none have been specifically targeted for treating binge drinking. Here, we assessed the effectiveness of the dopamine/norepinephrine re-uptake inhibitor, bupropion (BUP), alone and in combination with naltrexone (NAL), to reduce binge-like and chronic ethanol (EtOH) intake in mice. While BUP is an FDA-approved drug that is currently used to treat depression and nicotine dependence, there has been only limited investigation to assess the ability of BUP to reduce EtOH intake. METHODS: Male C57BL/6J mice were tested with 20% (v/v) EtOH using "drinking in the dark" (DID) procedures to model binge-like EtOH intake and following intermittent access to EtOH (IAE). In Experiment 1, mice were given intraperitoneal (i.p.) injection of 0, 20, or 40 mg/kg BUP 30 minutes before DID testing; in Experiment 2, mice were given i.p. injection of vehicle, BUP (20 mg/kg), NAL (3 mg/kg), or BUP + NAL (20 and 3 mg/kg, respectively) 30 minutes before DID testing; and in Experiment 3, mice were given i.p. injection of 0, 20, 40, or 60 mg/kg BUP 30 minutes before EtOH access after mice had 16 weeks of IAE. RESULTS: BUP dose dependently blunted EtOH intake with DID procedures and after 16 weeks of IAE. Administration of subthreshold doses of BUP + NAL also reduced binge-like EtOH intake. Finally, BUP failed to reduce consumption of a 3% (w/v) sucrose solution. CONCLUSIONS: BUP, alone and in combination with NAL, may represent a novel approach to treating binge EtOH intake. We are currently assessing the efficacy of BUP to curb binge drinking in a phase II clinical trial experiment.
Assuntos
Dissuasores de Álcool/administração & dosagem , Consumo Excessivo de Bebidas Alcoólicas/tratamento farmacológico , Bupropiona/administração & dosagem , Inibidores da Captação de Dopamina/administração & dosagem , Etanol/administração & dosagem , Naltrexona/administração & dosagem , Animais , Consumo Excessivo de Bebidas Alcoólicas/psicologia , Depressores do Sistema Nervoso Central/administração & dosagem , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Masculino , Camundongos , Camundongos Endogâmicos C57BL , AutoadministraçãoRESUMO
BACKGROUND: The Sweet Taste Test (STT) measures hedonic responses to sweet tastes and has been linked to both alcoholism and to a family history of alcoholism. However, STT response profiles in unipolar major depressive disorder (MDD), a disorder characterized by anhedonia, have been minimally investigated. METHODS: Twelve adults with and 15 adults without MDD participated in two identical STT assessments separated by approximately 12 weeks. Between assessments, MDD outpatients received Behavioral Activation Therapy for Depression, a psychotherapy modality designed to increase engagement with rewarding stimuli and reduce avoidance behaviors. Primary-dependent measures included sensitivity to sucrose, hedonic response to sucrose, and designation as a Sweet-Liker or Sweet-Disliker. RESULTS: A total of 75% of adults with MDD were treatment responders. There were no significant differences in STT response profiles between groups overall or at either timepoint. Furthermore, STT profiles of MDD participants did not differ after psychotherapy, relative to baseline. CONCLUSIONS: Findings suggest that although anhedonia is a symptom of MDD, the disorder is not characterized by altered responses to sweet tastes. Implications and future directions are discussed.
Assuntos
Transtorno Bipolar/psicologia , Transtorno Depressivo Maior/psicologia , Sacarose/administração & dosagem , Paladar , Adulto , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/terapia , Estudos de Casos e Controles , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicoterapia , Adulto JovemRESUMO
AIM: We tested the hypothesis that high novelty seeking (NS; a trait that promotes experimentation) and hedonic response to sweet taste (a trait that may reflect processing of hedonic stimuli) act independently to increase the risk for having alcohol-related problems in young adults. METHODS: The study was conducted in 158 healthy subjects (age 20-25 years) with no lifetime history of alcohol and/or drug abuse/dependence. NS was evaluated using the Tridimensional Personality Questionnaire. Pleasurable response to sweet taste was tested, using a sweet taste test to identify sweet likers (SL; those preferring the strongest offered sucrose solution) and sweet dislikers (SDL; those preferring weaker sucrose solutions). RESULTS: NS score, but not SL/SDL status, was positively correlated with drinks per month (P = 0.0054) and drinks per drinking day (P = 0.021). When tested individually, both NS and SL/SDL status predict having alcohol-related problems (NS: odds ratio [OR] = 5.3, P = 0.0016 and SL/SDL: OR = 5.8, P = 0.0001) with an OR similar to positive family history of alcoholism status (OR = 5.7, P = 0.0007). The combination of SL status and high NS score (greater than gender-specific 70th percentile) greatly increased the estimated odds of having alcohol-related problems (OR 27.5, P < 0.0001). CONCLUSIONS: These results support the hypothesis that high NS and SL phenotypes are independently associated with risk of alcohol-related problems. The combination of both phenotypes greatly increases the likelihood of alcohol-related problems. Although confirmation is necessary, this suggests that these phenotypes could contribute to improved methods to assess risk for alcohol-related problems and provide additional insight into processes underlying progression to alcohol-related problems.
Assuntos
Alcoolismo/genética , Comportamento Exploratório/fisiologia , Preferências Alimentares/fisiologia , Fenótipo , Sacarose/administração & dosagem , Paladar/fisiologia , Adulto , Alcoolismo/psicologia , Feminino , Preferências Alimentares/psicologia , Humanos , Masculino , Adulto JovemRESUMO
AIMS: To investigate the relationship between the sweet liking/sweet disliking phenotype (a putative probe of brain opioid function), craving for alcohol and response to treatment with naltrexone in individuals with alcohol dependence. METHODS: Forty individuals with alcohol dependence were enrolled in a 12-week open-label study of 50 mg of naltrexone with four sessions of motivational enhancement therapy. Prior to treatment, individuals completed a sweet preference test and the Penn Alcohol Craving Scale. Subjects were categorized as sweet liking (SL), n = 15, or sweet disliking (SDL), n = 25, via a standard sweet tasting paradigm. The sweet tasting results were blinded to the subjects and to treatment staff. SL status, pretreatment craving and their interaction were examined as predictors of frequency of abstinent days and heavy drinking days during treatment with naltrexone. RESULTS: SL and SDL subjects achieved similar reductions in percent heavy drinking days with treatment. During treatment, SDL subjects had 48% abstinent days compared to 30% for SL subjects (P = 0.034). Pretreatment craving did not predict % heavy drinking days or % abstinent days. An interaction effect was found between the SL/SDL phenotype and pretreatment craving such that SL subjects with high craving demonstrated higher rates of percent abstinent days whereas SDL subjects with high craving demonstrated lower rates of percent abstinent days, P < 0.001. CONCLUSIONS: These findings indicate that the SL/SDL phenotype may predict variation in response to naltrexone and/or counseling treatment. Furthermore, the SL/SDL phenotype may interact with craving to provide a more robust prediction of outcome with naltrexone or counseling.
Assuntos
Alcoolismo/tratamento farmacológico , Comportamento Aditivo/tratamento farmacológico , Naltrexona/uso terapêutico , Fenótipo , Paladar/genética , Adulto , Alcoolismo/genética , Alcoolismo/psicologia , Comportamento Aditivo/genética , Comportamento Aditivo/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Naltrexona/farmacologia , Inquéritos e Questionários , Paladar/efeitos dos fármacos , Resultado do TratamentoRESUMO
The purpose of the present study was to examine association between hedonic response to sweet taste and a mood altering effect associated with eating sweet foods and impaired control over eating sweets. Participants (n=163, 39% males) rated a series of sucrose solutions for intensity of sweetness and palatability and completed a newly developed 12-item Sweet Taste Questionnaire (STQ). It was shown that STQ identifies two factors in the individual's attitude towards sweet foods: sensitivity to the mood altering effect of sweets and impaired control over eating sweet foods. Individuals preferring the taste of the strongest offered sucrose concentration reported a stronger mood altering effect associated with eating of sweet foods and were more likely to have an impaired control over eating sweets than the rest of the group. Women generally had higher scores on both factors compared to men. The results of the present study support the hypothesis that hedonic response to sweet taste is associated with elevated sensitivity to mood altering effects of sweet foods and impaired control over eating sweets.
Assuntos
Afeto , Apetite , Carboidratos da Dieta/administração & dosagem , Comportamento Alimentar , Preferências Alimentares , Controle Interno-Externo , Sacarose/administração & dosagem , Paladar , Adulto , Consumo de Bebidas Alcoólicas/psicologia , Ansiedade/psicologia , Depressão/psicologia , Feminino , Humanos , Masculino , Motivação , Resposta de Saciedade , Estudantes/psicologia , Inquéritos e QuestionáriosRESUMO
IMPORTANCE: Identification of moderators of the response to naltrexone hydrochloride treatment for alcohol dependence could improve clinical care for patients with alcohol use disorders. OBJECTIVE: To investigate the preliminary finding that the sweet-liking (SL) phenotype interacts with a high level of craving for alcohol and is associated with an improved response to naltrexone in alcohol dependence. DESIGN, SETTING, AND PARTICIPANTS: This 12-week double-blind, randomized, placebo-controlled clinical trial was conducted from February 1, 2010, to April 30, 2012, in an academic outpatient medical center. Eighty actively drinking patients were randomized by the SL (n = 22) or the sweet-disliking (SDL) (n = 58) phenotype and by pretreatment high (n = 40) or low (n = 40) craving for alcohol, with high craving defined as greater than the median. Patients and staff were blinded to categorization. Patients were excluded for unstable medical or psychiatric illness, including dependence on drugs other than nicotine. Four patients (2 in the placebo arm and 2 in the naltrexone arm) stopped medication therapy because of adverse effects. Data were analyzed from January 15, 2013, to May 15, 2016, based on intention to treat. INTERVENTIONS: Oral naltrexone hydrochloride, 50 mg/d, or daily placebo with weekly to biweekly brief counseling. MAIN OUTCOMES AND MEASURES: The a priori hypothesis tested SL/SDL phenotype, pretreatment craving, and their interaction as moderators of frequency of abstinent and heavy drinking days during treatment, assessed with the timeline follow-back method. RESULTS: Eighty patients were randomized (57 men [71%]; 23 women [29%]; mean [SD] age, 47.0 [8.6] years). A nonsignificant effect of naltrexone on heavy drinking was noted (4.8 fewer heavy drinking days; Cohen d = 0.45; 95% CI, -0.01 to 0.90; F1,67 = 3.52; P = .07). The SL phenotype moderated the effect of naltrexone on heavy drinking (6.1 fewer heavy drinking days; Cohen d = 0.58; 95% CI, 0.12-1.03; F1,67 = 5.65; P = .02) and abstinence (10.0 more abstinent days; Cohen d = 0.57; 95% CI, 0.11-1.02; F1,67 = 5.36; P = .02), and high craving moderated heavy drinking (7.1 fewer heavy drinking days; Cohen d = 0.66; 95% CI, 0.20-1.11; F1,67 = 7.37; P = .008). The combination of the SL phenotype and high craving was associated with a strong response to naltrexone, with 17.1 fewer heavy drinking days (Cohen d = 1.07; 95% CI, 0.58-1.54; F1,67 = 19.33; P < .001) and 28.8 more abstinent days (Cohen d = 0.72; 95% CI, 0.25-1.17; F1,67 = 8.73; P = .004) compared with placebo. CONCLUSIONS AND RELEVANCE: The SL phenotype and a high craving for alcohol independently and particularly in combination are associated with a positive response to naltrexone. The SL/SDL phenotype and a high craving for alcohol merit further investigation as factors to identify patients with alcohol dependence who are responsive to naltrexone. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01296646.
Assuntos
Alcoolismo/genética , Alcoolismo/reabilitação , Fissura/efeitos dos fármacos , Fissura/fisiologia , Naltrexona/uso terapêutico , Fenótipo , Paladar/genética , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Temperança , Resultado do TratamentoRESUMO
BACKGROUND: The relationship between a hedonic response to sweet tastes and a propensity to excessive alcohol drinking is supported by both animal and human studies. This study was designed to test the hypothesis that the genetic risk for alcoholism as measured by a paternal history of alcoholism in young social drinkers is associated with sweet-liking, defined as rating the strongest offered sucrose solution (i.e., 0.83 M) as the most palatable during the standard sweet test. METHODS: Participants were 163 subjects (39% male) without a lifetime history of alcohol or drug abuse or dependence. Eighty-one subjects had a paternal history of alcoholism (FH+), and 82 did not (FH-). Each subject rated a series of sucrose solutions for intensity of sweetness and palatability. Subjects were categorized as sweet-likers if they rated the highest sucrose concentration as the most pleasurable. RESULTS: The estimated odds of being a sweet-liker were 2.5 times higher for FH+ than for FH- subjects. FH+ subjects disliked the tastes of the two weakest offered sucrose concentrations (0.05 and 0.10 M), whereas FH- subjects reported these tastes to be neutral. CONCLUSIONS: The results of this study support the hypothesis that sweet-liking is associated with a genetic vulnerability to alcoholism.
Assuntos
Alcoolismo/genética , Sacarose/farmacologia , Paladar/efeitos dos fármacos , Paladar/genética , Adulto , Distribuição de Qui-Quadrado , Feminino , Humanos , Modelos Logísticos , MasculinoRESUMO
BACKGROUND: The relationship between a hedonic response to sweet taste and a propensity to excessive alcohol drinking is supported by both animal and human studies. There is evidence indicating that the tendency to rate more concentrated sweet solutions as the most pleasurable (i.e., sweet liking) is associated with the genetic vulnerability to alcoholism. However, sweet liking by itself is insufficient to predict the alcoholic status of the individual. Our previous study indicated that alcoholic status can be predicted by a combination of hedonic response to sweet taste and personality profile as measured by the Tridimensional Personality Questionnaire (TPQ). This study was designed to further test this hypothesis. METHODS: Participants were 165 patients admitted to a residential treatment program for the treatment of alcoholism, drug dependence and/or interpersonal problems secondary to substance-abusing family members. In addition to a routine medical examination, on the 24th day after admission, patients completed the TPQ, the standard sweet taste test was conducted, and paternal family history of alcoholism was evaluated. RESULTS: Sweet liking was strongly associated with a paternal history of alcoholism. The odds of receiving an alcohol dependence diagnosis were shown to increase, on the average, by 11% for every one-point increase in the TPQ novelty-seeking score in sweet-liking but not in sweet-disliking subjects. Gender contributed independently to the probability of alcohol dependence, with males exhibiting higher rates of alcoholism than females. CONCLUSIONS: These findings support the hypothesis that a hedonic response to sweet taste is associated with a genetic risk for alcoholism. Alcoholic status may be predicted by a combination of sweet liking, the TPQ novelty-seeking score, and gender in a mixed group of alcoholic, polysubstance-dependent, and psychiatric patients.