Tabaco e alcool durante a adolescência: efeitos na memória e aprendizado e no sistema colinérgico central

Abstract

Studies show a strong relationship between smoking and alcohol consumption, so that the co-occurrence of alcohol and smoking is very common. This study evaluated the effects of tobacco, ethanol and double exposure to tobacco + ethanol in memory/ learning and central cholinergic system of mice during exposure and withdrawal. From the 30th to the 45th postnatal day (PN30-PN45), Swiss mice were exposed to cigarette smoke generated from research cigarettes (0.7 mg of nicotine, 9.4 mg of tar and 12 mg of CO) in a cigarette smoke machine 8h/day and/or i.p. ethanol injections (2g/kg, 25%, v/v) on alternate days. For this study four experimental groups were used: SMK + ETOH (animals exposed to cigarette smoke and i.p. ethanol injections), SMK (exposure to cigarette smoke and i.p. saline), ETOH (i.p. ethanol and air exposure) and VEH (animals received ip saline and air exposure). At the end of the period of exposure (PN44-45) during a short period of drug withdrawal (PN49-50) and at adulthood (PN74-75) these animals were submitted to the Passive Avoidance behavioral test, which evaluates memory / learning. In the first testing day (PN44 / PN49 / PN74), animals are placed on a platform and are allowed 3 min to descend from it, at which time they receive a foot shock (0.3 mA, 3 s). Three (T3) and 24h (T24) after the initial testing, animals are retested (shock is not administered). The latency to fall of platform was used as an index of memory / learning. After the last test, animals are sacrificed and the brains collected for further analysis. To investigate the central cholinergic system we assessed choline acetyltransferase (ChAT) activity, binding of [3H] hemicholinium-3 (HC-3) to the presynaptic choline transporter and the acetylcholinesterase (AChE) activity in hippocampus. We found that during exposure, ETOH, FUM, and SMK + ETOH groups presented lower latency to descend from the platform at T3, which was also observed at T24 for SMK and SMK + ETOH groups. In the short period of withdrawal, we found that at T24 male mice from SMK + ETOH group presented shorter latency to descend from the platform. At adulthood, we found no significant differences in the Passive Avoidance test. During exposure, there were no changes in ChAT, HC-3 and AChE. There were no changes in AChE activity in the other two analyzed time points. Females from the SMK group had lower ChAT activity at five days of withdrawal, whereas at adulthood, the decreased activity was observed in SMK, ETOH and SMK + ETOH groups. Regarding HC-3 binding, in the short period of withdrawal, males from the SMK + ETOH showed increased binding, the same effect observed at adulthood in male and female mice from ETOH and SMK groups. Thus, cigarette smoke, ethanol and the combined exposure during adolescence of mice negatively affect performance in the Passive Avoidance memory / learning test and the central cholinergic system.