Search

It is about half a century ago when the so-called "Wise model" to study alcohol drinking behavior in rats was established. The model was based on voluntary intermittent access to increasing concentrations of alcohol. We aimed to establish a model of alcohol craving and used an extinction test on withdrawal days 1 and 10 to study motivation for alcohol. For this purpose, the alcohol drinking training was paired with light cues to establish conditioning. The extinction test was carried out without alcohol but in the presence of light cues and empty bottles. The outcome measures were number of visits, nosepokes, and licks in the conditioned corner where the number of nosepokes represents how much mice "want" alcohol and number of licks shows how much mice "like" alcohol. The number of nosepokes during withdrawal is a measure of craving. Late withdrawal craving was found when intermittent alcohol access was carried out in the automated cages. In this case, we observed a significant increase in the number of nosepokes on both withdrawal days 1 and 10 as compared to water control. The number of nosepokes in the withdrawal days did not correlate with alcohol dose, but number of nosepokes on withdrawal day 1 correlated with the number of nosepokes on the last training day. Although we did not observe incubation of alcohol craving after withdrawal, the craving was increased at the late time point. We conclude that we have established a new tool to study alcohol drinking behavior and craving in female mice.

Evidence for an interaction between nicotine and morphine has been found in several studies. In the present study mice withdrawn from a 7-week oral nicotine treatment were administered morphine, following which their locomotor activities were recorded and the concentrations of dopamine, 5-hydroxytryptamine (5-HT), noradrenaline and their metabolites were measured in the caudate putamen (CPu) and nucleus accumbens (NAc). For comparison, the effect of cocaine on locomotor activity was studied in mice withdrawn from nicotine. Morphine (15 mg/kg s.c.) enhanced locomotor activity significantly more in the nicotine-withdrawn mice than in the controls, whereas cocaine (20 mg/kg i.p.) stimulated the locomotor activity similarly in the nicotine-withdrawn and in the control mice. Morphine (10 mg/kg s.c.) elevated dopamine and 5-HT metabolites to the same degree in the NAc of the nicotine-withdrawn and the control mice. However, in the CPu morphine enhanced the metabolism of dopamine and also that of 5-HT in the nicotine-withdrawn mice but not in the controls. In addition, the basal concentrations of dopamine metabolites were reduced in the CPu of the nicotine-withdrawn mice. Thus, the enhancement of morphine-induced locomotor activation in the nicotine-withdrawn mice could be related to nicotine-induced changes in the regulation of the nigrostriatal dopaminergic and serotonergic systems.