Original Article

Neuropsychopharmacology (2009) 34, 1609–1624; doi:10.1038/npp.2008.220; published online 17 December 2008

Nicotine Exposure during Adolescence Induces a Depression-Like State in Adulthood

Sergio D Iñiguez1,2, Brandon L Warren1,2, Eric M Parise1, Lyonna F Alcantara1, Brittney Schuh1, Melissa L Maffeo1, Zarko Manojlovic1 and Carlos A Bolaños-Guzmán1

1Program in Neuroscience, Department of Psychology, Florida State University, Tallahassee, FL, USA

Correspondence: Dr CA Bolaños-Guzmán, Program in Neuroscience, Department of Psychology, Florida State University, 1107 West Call Street, Tallahassee, FL 32306-4301, USA. Tel: +1 850 644 2627; Fax: +1 850 645-7518; E-mail: bolanos@psy.fsu.edu

2These authors contributed equally to this work.

Received 28 July 2008; Revised 13 November 2008; Accepted 14 November 2008; Published online 17 December 2008.

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Abstract

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.

Keywords:

adolescence, bupropion, depression, fluoxetine, nicotine, rats

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