Adolescent or adult exposure to nicotine in Swiss mice: age-dependent and -independent effects on open field and elevated plus maze behaviors and on hormonal parameters associated with anxiety.

Adolescence is a critical period of vulnerability to smoking initiation. However, the neurobiological basis of this association is not well understood. Hence, here we evaluated behavioral parameters, tyrosine hydroxylase content, and catecholamine and corticosterone levels of Swiss mice exposed to nicotine (NIC; 50 μg/mL in 2% saccharin to drink) or vehicle either from postnatal day (PN) 30 to PN46 (adolescents) or from PN75 to PN91 (young adults). Behavioral tests, tissue harvesting, and blood collection occurred in one of three time points: by the end of exposure, after a short withdrawal (4/5 days; SHRT-W) or after a long withdrawal (9/10 days; LNG-W). At SHRT-W, our results in the elevated plus maze (EPM) showed increased anxiety-like behavior in NIC mice when compared to controls, irrespective of age, while, in the open field (OF), an age-independent reduction in anxiety was noted. Adolescent NIC mice showed increased locomotion in the EPM throughout withdrawal, while, in the OF, both adolescent and young adult NIC mice showed increased locomotion at SHRT-W. An age-dependent adolescent-only reduction in corticosterone was observed at SHRT-W in NIC mice. At LNG-W, corticosterone was increased in young adults, particularly in females, compared to controls. The similarity in anxiety-like behavior between adolescents and young adults suggests that the period of vulnerability to nicotine extends beyond the end of adolescence. For the most part, behavioral data failed to reflect changes in neuroendocrine parameters associated with stress response and anxiety. Further investigation of the mechanisms for regulation of behavioral responses to nicotine withdrawal is warranted.