Maturational increases in c-fos expression in the ascending dopamine systems

The unique maturational period of adolescence is replete with numerous chan ges in anatomy and function that may yield clues as to why drug abuse emerg es at this stage. The behavioral effects of amphetamine are diminished duri ng periadolescence (35 days) relative to younger (21 days) and older (> 60 days) rats, prompting us to examine amphetamine effects on neuronal activat ion with the immediate early gene, c-fos. Amphetamine (1 and 5 mg/kg, i.p.) increased c-fos immunoreactivity in rats 21, 35, and 60 days of age in a d ose-dependent manner. When expressed as a percentage of vehicle for each ag e, amphetamine-induced effects on c-fos immunoreactivity were higher at 21 days of age compared with the effects at 35 and 60 days of age in the nucle us accumbens core and shell, striatum, and prefrontal cortex. These data pr ovide a possible reason as to why stimulants produce dysphoria in children, before transitioning to euphoria during adolescence. Implications of these results are discussed for stimulant use in a pediatric population and the development of drug abuse. (C) 2001 Wiley-Liss, Inc.