Behavioral effects of combined environmental enrichment and chronic nicotine administration in male NMRI mice

• EE mice gained less body weight and displayed a higher fluid intake than SE mice.
• EE induces anxiolytic-like effects in the elevated plus-maze.
• EE mice displayed lower exploration and spontaneous motor activity than SE mice.
• Chronic nicotine treatment decreases motor activity but did not improve learning.
• Need to evaluate the interaction between EE and cognitive effects of nicotine.

Environmental enrichment (EE) is an experimental paradigm which provides sensory, social, physical and cognitive stimulation for rodents. Experimental evidence indicates that this type of housing induces different neurobiological and behavioral changes. However, few studies have evaluated the consequences of combined exposure to an enriched environment and nicotine administration during a critical period of development such as adolescence. Taking into account previous studies, it can be hypothesized that a chronic treatment with nicotine would modulate the effects of rearing animals in enriched environments. In the current study, our main aim was to evaluate the effects of EE and chronic nicotine administration on physiological parameters (weight, fluid intake and cotinine levels), motor activity, exploratory behavior, anxiety and learning in male NMRI mice. Half of the mice (n = 32) were exposed to an enriched environment (EE) and the other half (n = 32) were housed in standard environments (SE) with or without oral nicotine administration (100 μg/ml). After 3 weeks, mice were evaluated in a behavioral battery that included an elevated plus-maze, a hole board, an actimeter and an inhibitory avoidance task. Blood cotinine levels were measured in an additional group of 32 mice in order to confirm nicotine intake. Results indicated that mice reared in an enriched environment gained less body weight and displayed higher fluid intake than those maintained in a standard environment. EE reduced motor activity, exploratory behavior and anxiety, whereas it enhanced inhibitory avoidance learning. In relation to the effects of chronic nicotine treatment, the data reflected a lower increase in body weight and a reduced fluid intake in nicotine-treated mice. In the elevated plus-maze, nicotine induced a reduction of total arm entries and rearings. Cotinine levels were higher in mice that received oral nicotine than in the control group. We conclude that the EE paradigm applied in this study induces physiological and behavioral changes in NMRI mice. Chronic nicotine treatment diminished motor activity displayed by mice in the elevated plus-maze but did not have significant effects on inhibitory avoidance learning. Future studies should explore in greater depth the interaction between environmental factors and nicotine administration using longer periods of EE, a wider range of doses and/or other cholinergic agonists, acute drug administration, and sequential exposure to nicotine and EE.