CONICET | Buscador de Institutos y Recursos Humanos

The endocannabinoid system (eCB) is involved in the modulation of the reward system and participates in the reinforcing effects of different drugs of abuse, including alcohol. The most abundant receptor of the eCB system in the nervous central system is the CB1 receptor (CB1R), which is presynaptic and predominantly expressed in areas involved in drug addiction, such as the nucleus accumbens, the ventral tegmental area (VTA), the substantia nigra and the raphe nucleus. CB1R is expressed in early stages during development and reaches maximum levels during early adolescence. In addition, the other cannabinoid receptor CB2R has been found also expressed in the CNS, at the postsynaptic level, and this receptor has also been implicated in drug abuse, such as alcohol. Therefore, to study the participation of the eCB system in ethanol (EtOH) preference and anxiety during adolescent development, early-adolescent mice were exposed to cannabinoid agonist WIN 55,212-2 (WIN) for 5 consecutive days. Although no statistically significant differences were found in the intake and EtOH preference between the two experimental groups, WIN exposed mice exhibited a tendency to a higher EtOH preference. WIN exposure produce an anxiogenic behavior.The following morphological consequences are present in brain of WIN exposed adolescent mice:There are not differences in the expression of tyrosine hydroxylase and number of dopaminergic neurons in tegmental ventral area and substantia nigra. Higher dendritic ramifications and fewer dendritic spines in neurons of the subsantia nigra pars compacta.Serotonergic neurons of dorsal raphe nucleus showed an increase in tryptophan hydroxylase-expressing neurons. CB1R are not present in neuronal somata of serotonergic neurons.Then, WIN in adolescent drinking mice produce changes in serotonergic and dopaminergic neurons that could be explain the anxiogenic behavior and the trend to alcohol preference observed.