Indication of methamphetamine-induced reactive synaptogenesis in the prefrontal cortex of gerbils ( Meriones unguiculatus)

A single dose of methamphetamine (25 mg/kg i.p.) was administered to young adult gerbils ( Meriones unguiculatus) aged 90 days and the number of spices was determined along 40-μm segments of basal, lateral and apical dendrites of pyramidal cells in layers III and V of the prefrontal cortex, after 1.5, 7, 20 and 30 days. The density of spines rapidly increased by more than 80% within 7 days after drug challenge, and subsequently returned to the original normal values within about 2 weeks. Thirty days after drug administration the density of dendritic spines was slightly, but significantly, less than control values (about 5%). The density of spines was likewise affected in layer III and V neurones, irrespective of the spatial domain of their dendritic ramifications. Since several lines of investigation indicate that methamphetamine can cause the destruction of dopaminergic nerve terminals in the mammalian forebrain, the present results are discussed against the background of current concepts about reactive synaptic reorganization and adaptive remodelling of neural circuits in the central nervous system.