Adolescent nicotine abstinence increases anxiety and depressive-like behaviors, alcohol consumption, oxidative stress and inflammatory response accompanied by attenuated serotonergic/dopaminergic and cholinergic function in rats

During the last decade adolescent nicotine exposure has become a growing concern worldwide and the significance of this issue has even been further highlighted by recent evidence indicating long-term behavioral complications associated with nicotine abstinence. In addition, nicotine has been suggested to serve as a gate for inclination and susceptibility to other drugs of abuse such as alcohol. The present study was designed to investigate how nicotine abstinence during adolescence may affect the expression of anxiety- and depressive-like signs, as well as the alcohol consumption in adult rats. In order to quantify the behavioral manifestations, open filed test, elevated plus maze, marble burying test and forced swimming test were applied. In addition to these behavioral tests, biochemical markers of oxidative stress, inflammatory cytokines, brain monoaminergic status and cholinergic transmission were assessed in cortical tissues. Moreover, involvement of serotonergic and dopaminergic functions were further investigated by administration of MAO-B inhibitor and SSRI drugs (selegiline and sertraline). Results indicated that nicotine abstinence increases the physical signs of anxiety and depression in parallel with exacerbation of oxidative and inflammatory profile and attenuation of monoaminergic and cholinergic tone in cortex. Another interesting finding was enhancement of ethanol drinking in nicotine-abstained group, compared to saline-treated rats. Treatment by higher doses of selegiline/sertraline could markedly prevent the mentioned behavioral and biochemical consequences induced by nicotine abstinence.