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

https://doi.org/10.1016/0014-2999(93)90937-DGet rights and content

Abstract

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.

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      Although the precise molecular signal cascade that mediates the directed outgrowth is not deciphered yet, it is known that NMDA receptor activation is a necessary condition to establish the reorientation of the dendritic arbors during development (Datwani et al., 2002). Following a single injection of methamphetamine (MA), we saw pronounced reactive structural plasticity occurring in the prefrontal cortex of gerbils (Meriones unguiculatus) (Dawirs et al., 1991; Dawirs et al., 1993). MA apparently acts as chemical scissors for the developing meso-prefrontal DA fibres (Dawirs et al., 1994, 1997) and entails measurable deficits in prefrontal cortex related behaviour (Dawirs et al., 1996).

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