Behavioral and neurochemical vulnerability during adolescence in mice: studies with nicotine.
People are very likely to start psychoactive drug use during adolescence, an earlier onset being associated with a higher risk of developing addiction later in life. In experiment I, Pre- (postnatal day (pnd) 23-35), Mid- (pnd 36-48), or Post- (pnd 49-61) adolescent mice underwent a restricted-drinking period (2 h/day for 12 days), one bottle containing water and the other containing nicotine (10 mg/l) or water. After this period, Mid-adolescents showed prominent exploration and reduced anxiety in the plus-maze. This ontogenetic profile was dampened by nicotine consumption. After 2 months, these mice were tested in a novel environment (30 min/day for 3 days). Locomotor-habituation profiles were specifically disrupted by nicotine consumption during Mid-adolescence, suggesting this age as a critical period. In experiment II, Mid-adolescent (pnd 35-44) and adult (pnd > 70) mice were pretreated with nicotine (0, 0.03, 0.10, 0.30 mg/kg/day for 10 days). Acute nicotine administration had opposite effects on anxiety in adolescents and adults. At 2 months after pretreatment, we measured levels of AMPA GluR2/3 subunits, thought to be involved in the control of addictive behaviors. Nicotine exposure during Mid-adolescence dose-dependently downregulated these subunits in the striatum and hippocampus, but comparable exposure during adulthood had either opposite or no effects. NMDA NR2A/B subunits were affected by nicotine, but without age-related differences. The present data identified a nicotine-vulnerable age window, characterized by long-term disruption of locomotor habituation and downregulation of AMPA receptors. These findings support neurobiological vulnerability to drugs in adolescent humans.
Adriani
Walter
W
Section of Behavioral Pathophysiology, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanita', Roma, Italy.
Granstrem
Oleg
O
Macri
Simone
S
Izykenova
Galina
G
Dambinova
Svetlana
S
Laviola
Giovanni
G
D000375:Aging / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D004327:Drinking Behavior / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018091:Receptors, AMPA / Q000187:drug effects; D017470:Receptors, Glutamate / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D018722:Nicotinic Agonists; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D009538:Nicotine