RESUMEN
RATIONALE: Studies with laboratory animals and humans suggest that dopamine may play a role in maintaining cigarette smoking behavior via its interactions with nicotine. OBJECTIVES: This study was designed to replicate and extend previous findings showing that the dopamine D2 antagonist, haloperidol, produces blockade of smoking reward and compensatory increases in smoking. METHODS: We studied 20 subjects in a 2x3 within-subjects design, with nicotine-containing or denicotinized cigarettes crossed with oral placebo, haloperidol 1 mg, or haloperidol 2 mg. Subjects attended six sessions during which they received one of the cigarette/drug combinations, and smoked under both controlled and ad libitum conditions. Cigarette and mood ratings and smoking behavior were assessed. RESULTS: Haloperidol reduced the number of cigarettes smoked and the carbon monoxide boost associated with both types of cigarettes, at doses that did not appear to produce clinically significant behavioral effects. CONCLUSIONS: Dopamine appears to play a role in mediating smoking behavior, but this may occur through a non-nicotine mechanism.
Asunto(s)
Antagonistas de Dopamina/uso terapéutico , Haloperidol/uso terapéutico , Nicotina/farmacología , Agonistas Nicotínicos/farmacología , Fumar/tratamiento farmacológico , Adolescente , Adulto , Análisis de Varianza , Método Doble Ciego , Femenino , Humanos , Masculino , Fumar/psicologíaRESUMEN
The opioid antagonist naltrexone has been shown to be effective in the treatment of alcoholism, possibly by dampening the subjective effects of ethanol. However, naltrexone does not consistently attenuate the effects of ethanol in social drinkers in laboratory-based challenge studies. In the present study, 25 healthy volunteers, who were either light drinkers (mean = 3 drinks per week) or moderate drinkers (mean = 16 drinks per week), participated in six evening sessions. At each session, subjects ingested a capsule containing naltrexone (25 or 50 mg) or placebo, and 1 hr later they consumed a beverage containing ethanol (0.25 g/kg, equivalent to about two standard alcoholic drinks) or placebo. Subjects received all combinations of pretreatments and beverages. They completed self-report mood questionnaires and psychomotor tests at regular intervals. This low dose of ethanol produced modest but significant effects on self-report measures such as ratings of feeling a drug effect and of liking the drug effect. However, naltrexone (25 or 50 mg) pretreatment had no dampening effect on subjects' responses to ethanol. These results indicate that acute doses of naltrexone that are effective when administered chronically to alcoholics do not attenuate the acute effects of a low dose of ethanol in non-problem drinkers.
Asunto(s)
Consumo de Bebidas Alcohólicas/psicología , Intoxicación Alcohólica/psicología , Naltrexona/farmacología , Antagonistas de Narcóticos/farmacología , Medio Social , Administración Oral , Adulto , Consumo de Bebidas Alcohólicas/prevención & control , Intoxicación Alcohólica/prevención & control , Nivel de Alerta/efectos de los fármacos , Atención/efectos de los fármacos , Pruebas Respiratorias , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Etanol/farmacocinética , Femenino , Humanos , Masculino , MotivaciónRESUMEN
This study examined the effects of ethanol preloading on preference for tobacco cigarettes in 10 nicotine-dependent volunteers. The crossover, double-blind study involved pretreating participants with 0, 0.2, 0.4 or 0.8 g/kg ethanol immediately prior to a task in which cigarettes and/or money could be earned. Tobacco cigarette preference was measured using the number of responses performed and reinforcers earned on a series of concurrent random-ratio schedules that yielded tobacco and money reinforcers. In addition to the preference measures, subjective effects and psychomotor performance were assessed before beverage ingestion and at regular intervals afterwards. Ethanol induced alterations in mood and psychomotor performance in a dose-related fashion. However, preference for tobacco cigarettes was not affected by ethanol pretreatment. The present study suggests that the increase in cigarette smoking that is associated with ethanol consumption does not involve changes in smokers' preference for cigarettes.