Effects of Amphetamine on Serotoninergic and Gabaergic Expression of Developing Brain

Roles of age and withdrawal were explored in mechanisms underlying the action of amphetamine (Amph), by monitoring the serotonergic and GABAergic expression in key brain regions of the rat. Postnatal 21 and 60 day-old male rats were intraperitoneally injected with D-Amph, 5 mg/kg, or saline, three times daily for 14 days and then withdrawn from Amph for 0 or 14 days; these animals received single injections on day 15 (W0d) or day 29 ( W14d). Following Amph injections, though both age groups exhibited hyperlocomotion , stereotypy and behavioral sensitization, the juvenile showed 100-300% longer latencies to reach and 30%-42% shorter duration of maximal behavioral scores than the adult from day 2-29. Immunocytochemical analysis revealed down- regulation of 42-76% in 5-hydroxytryptamine (HT) immunoreactive processes in motor and somatosensory cortices , and hippocampus of both ages after Amph exposure at W0d. At W14d, the 5-HT resembled saline-control in the Amph- treated juvenile, whereas remained weakened in the adult. By contrast, densities of GAD67 (glutamic acid decarboxylase)- boutons were up-regulated by 35-545% in the neocortical areas, nucleus accumbens, caudate-putamen and hippocampus of all Amph- administered rats. After 14 days withdrawal, the juvenile recovered the decreased 5-HT fibers, but not the increased GABAergic, indicating unique roles of the two systems in response to Amph. (c) 2006 Elsevier Inc. All rights reserved