Age influences the effects of nicotine and monoamine oxidase inhibition on mood-related behaviors in rats.
BACKGROUND
Epidemiological studies have demonstrated a comorbidity of smoking with depression and anxiety, particularly during adolescence. However, few animal studies have considered possible synergistic interactions between nicotine and other tobacco smoke constituents, such as monoamine oxidase (MAO) inhibitors, in the regulation of mood.


OBJECTIVE
The aim of the study was to test the hypothesis that nicotine combined with the irreversible MAO inhibitor, tranylcypromine, will differentially affect depression- and anxiety-related behaviors in adolescent and adult rats.


METHODS
Nicotine (0, 0.05, 0.2 mg/kg, s.c.) and tranylcypromine (3 mg/kg, i.p.) were tested separately, or together, on male rats aged postnatal days 30 and 68, in three mood-related behavioral tests: forced swim test (FST), elevated plus maze (EPM), and open field.


RESULTS
Nicotine (0.2 mg/kg) in adults significantly decreased floating time in the FST and increased time spent in the open arm of the EPM, with no change in locomotor activity. Tranylcypromine pretreatment combined with nicotine (0.2 mg/kg) significantly increased locomotor activity and time spent in the center of the open field. Whereas nicotine alone had no significant effect on adolescents, it significantly increased locomotor activity and decreased floating time in the FST when combined with tranylcypromine pretreatment.


CONCLUSIONS
There is an age-dependent effect of nicotine, alone and in combination with MAO inhibition, on mood-related behaviors. Whereas nicotine alone induces mood improvement in adults, it has no effect on adolescents. Nicotine combined with tranylcypromine has unique, age-dependent effects. Thus, experimental studies of smoking should consider both age and other tobacco constituents, such as MAO inhibitors, as critical factors.
Villégier
Anne-Sophie
AS
Department of Pharmacology, School of Medicine, University of California, Irvine, CA 92697, USA. anne-sophie.villegier@ineris.fr
Gallager
Brittney
B
Heston
Jon
J
Belluzzi
James D
JD
Leslie
Frances M
FM
D000339:Affect / Q000187:drug effects*; D000367:Age Factors; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013550:Swimming; D014191:Tranylcypromine / Q000494:pharmacology*
D008996:Monoamine Oxidase Inhibitors; D014191:Tranylcypromine; D009538:Nicotine