Nicotine exposure during adolescence induces a depression-like state in adulthood.

There is a strong link between tobacco consumption and mood disorders. It has been suggested that afflicted individuals smoke to manage mood, however, there is evidence indicating that tobacco consumption can induce negative mood. This study was designed to investigate whether nicotine exposure during adolescence influences emotionality/behavioral functioning later in life. Adolescent (postnatal days, PD 30-44) male rats were treated with twice-daily injections of nicotine (0, 0.16, 0.32, or 0.64 mg/kg) for 15 consecutive days, and their behavioral reactivity to various behavioral paradigms (the elevated plus maze (EPM), sucrose preference, locomotor activity in the open field, and forced swim test (FST) was assessed 24 h (short term) or 1-month (long term) after exposure. Separate groups of adult rats received nicotine (0.32 mg/kg) to control for age-dependent effects. We report that nicotine exposure during adolescence-but not adulthood-leads to a depression-like state manifested in decreased sensitivity to natural reward (sucrose), and enhanced sensitivity to stress- (FST) and anxiety-eliciting situations (EPM) later in life. Our data show that behavioral dysregulation can emerge 1 week after drug cessation, and that a single day of nicotine exposure during adolescence can be sufficient to precipitate a depression-like state in adulthood. We further demonstrate that these deficits can be normalized by subsequent nicotine (0.32 mg/kg) or antidepressant (ie fluoxetine or bupropion; 10 mg/kg) treatment in adulthood. These data suggest that adolescent exposure to nicotine results in a negative emotional state rendering the organism significantly more vulnerable to the adverse effects of stress. Within this context, our findings, together with others indicating that nicotine exposure during adolescence enhances risk for addiction later in life, could serve as a potential model of comorbidity.

Antidepressant treatment can normalize adult behavioral deficits induced by early-life exposure to methylphenidate.

BACKGROUND: Methylphenidate (MPH) is prescribed for the treatment of attention-deficit/hyperactivity disorder. Exposure to MPH before adulthood causes behavioral deficits later in life, including anxiety- and depression-like behaviors and decreased responding to natural and drug rewards. We examined the ability of fluoxetine (FLX), a selective serotonin reuptake blocker, to normalize these MPH-induced behavioral deficits. METHODS: Male rats received MPH (2.0 mg/kg) or saline (VEH) during preadolescence (postnatal day [PD] 20-35). When adults, rats were divided into groups receiving no treatment, acute or chronic FLX, and behavioral reactivity to several emotion-eliciting stimuli were assessed. RESULTS: The MPH-treated rats were significantly less responsive to natural (i.e., sucrose) and drug (i.e., morphine) rewards and more sensitive to stress- and anxiety-eliciting situations. These MPH-induced deficits were reversed by exposure to FLX. CONCLUSIONS: These results indicate that exposure to MPH during preadolescence leads to behavioral alterations that endure into adulthood and that these behavioral deficits can be normalized by antidepressant treatment. These results highlight the need for further research to better understand the effects of stimulants on the developing nervous system and the potential enduring effects resulting from early-life drug exposure.