Maturational increases in c-fos expression in the ascending dopamine systems.
The unique maturational period of adolescence is replete with numerous changes in anatomy and function that may yield clues as to why drug abuse emerges at this stage. The behavioral effects of amphetamine are diminished during periadolescence (35 days) relative to younger (21 days) and older (>60 days) rats, prompting us to examine amphetamine effects on neuronal activation 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 dose-dependent manner. When expressed as a percentage of vehicle for each age, 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 nucleus accumbens core and shell, striatum, and prefrontal cortex. These data provide 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.
Andersen
S L
SL
Department of Psychiatry, Harvard Medical School, Laboratory of Developmental Psychopharmacology, Mailman Laboratories for Psychiatric Research, McLean Hospital, Belmont, Massachusetts 02478, USA. andersen@mclean.org
LeBlanc
C J
CJ
Lyss
P J
PJ
D000367:Age Factors; D000661:Amphetamine / Q000494:pharmacology; D019969:Amphetamine-Related Disorders / Q000378:metabolism*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005059:Euphoria / Q000187:drug effects / Q000502:physiology; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000697:Central Nervous System Stimulants; D016760:Proto-Oncogene Proteins c-fos; D000661:Amphetamine; D004298:Dopamine