RESUMO
According to the Pavlovian conditioning model, drug tolerance is modulated by drug-associated environmental cues. This study evaluated the contribution of drug-associated cues in the development of cross-tolerance to the tachycardic effects of nicotine from tobacco and alcohol in human subjects. Forty undergraduate students were recruited for this experiment, and each student was randomly assigned to one of two experimental conditions. Twenty students smoked nicotine-containing cigarettes in context A and placebo cigarettes in context B, and twenty students smoked nicotine-containing cigarettes in context B and placebo cigarettes in context A. A cross-tolerance test was carried out by dividing the subjects in each condition into two subgroups (n = 10). Each subgroup consumed alcohol in both contexts (A and B). The results of this experiment showed that cross-tolerance between nicotine and alcohol was exhibited only if the cross-tolerance test was carried out in the same context where tolerance had developed to the nicotine from tobacco. These results support the hypothesis that drug-associated environmental stimuli play a modulatory role in the development of cross-tolerance between nicotine from tobacco and alcohol.
De acuerdo con el modelo de condicionamiento pavloviano, las claves ambientales asociadas a la droga modulan la tolerancia a las drogas. Este estudio evaluó la contribución de las claves asociadas a la droga en el desarrollo de tolerancia cruzada a los efectos taquicárdicos de la nicotina de tabaco y el alcohol en sujetos humanos. En este experimento participaron cuarenta estudiantes universitarios. Cada estudiante fue asignado aleatoriamente a una de dos condiciones experimentales. Veinte estudiantes fumaron cigarros con nicotina en el Contexto A y placebo en el Contexto B y veinte estudiantes fumaron cigarros con nicotina en el Contexto B y placebo en el Contexto A. La prueba de tolerancia cruzada fue llevada a cabo dividiendo a los participantes de cada condición en dos subgrupos (n = 10), cada subgrupo consumió alcohol en cada uno de los contextos (A y B). Los resultados de este experimento muestran que la tolerancia cruzada entre nicotina y alcohol se presentó únicamente cuando la prueba de tolerancia cruzada se realizó en el mismo contexto donde se desarrolló la tolerancia a la nicotina del tabaco. Estos resultados concuerdan con la hipótesis de que los estímulos ambientales asociados a la droga juegan un papel modulador en el desarrollo de la tolerancia cruzada entre la nicotina del tabaco y el alcohol.
Assuntos
Preparações Farmacêuticas , Produtos do Tabaco , Tabagismo , Etanol , Humanos , NicotinaRESUMO
GABAB and 5-HT2C agonists are effective in attenuating the behavioral effects of psychostimulants. However, they induce adverse side effects when used in high doses. The previous evidence has suggested that the 5HT2C receptor activation effect could be produced by an increased release of GABA in the ventral tegmental area (VTA) and the consequent activation of GABAergic receptors. Therefore, the objective of this study was to evaluate the effects of joint administration of an intermediate dose of the GABAB agonist baclofen (3.0 mg/kg) with different doses of the 5HT2C agonist Ro60-0175 (0.3, 1.0, and 3.0 mg/kg) on the locomotor sensitization expression induced by the repeated administration of amphetamine (1.0 mg/kg). Our results showed an attenuation of the expression of sensitization in a dose-dependent manner with both agonists. In both cases, we observed a complete blockade at the highest dose. In addition, the intermediate dose of baclofen increased the effects of the three doses of Ro60-0175. These results support the role of the joint action of GABAB and 5-HT2C receptors in the effects of psychostimulants. However, it remains to be explored whether the observed effect can be attributed to receptors located in the VTA or the nucleus accumbens.
