Diffusion tensor imaging of cocaine-treated rodents

Abstract

Studies in cocaine-dependent human subjects have shown differences in white matter on diffusion tensor imaging (DTI) compared to non-drug using controls. It is not known whether the FA differences seen on DTI in white matter regions of cocaine-dependent humans result from a preexisting predilection for drug use or purely from cocaine abuse. To study the effect of cocaine on brain white matter, DTI was performed on 24 rats after continuous infusion of cocaine or saline for 4 weeks, followed by brain histology. Voxel-based morphometry analysis showed 18% decrease in fractional anisotropy (FA) in the splenium of corpus callosum (CC) in cocaine-administered animals relative to saline controls (P = 0.0001). On histology, significant increase in neurofilament expression (125%, P=0.0044) and decrease in myelin basic protein (40%, P = 0.031) was observed in the same region in cocaine-administered animals. This study supports the hypothesis that chronic cocaine use alters white matter integrity in human CC. Unlike humans, where the FA in the genu differed between cocaine users and non-users, the splenium was affected in rats. These differences between rodent and human findings could be due to a several factors that include differences in the brain structure and function between species and/or the dose, timing, and duration of cocaine administration.

Loss of lysophosphatidic acid receptor LPA1 alters oligodendrocyte differentiation and myelination in the mouse cerebral cortex

“…Because structural alterations in the corpus callosum involve axonal connections between the association cortices, the consequences are variable neural and behavioral effects, depending on the situation (van der Knaap and van der Ham 2011). Consequently, not only cortico-cortical disconnection disruptions affecting sensorimotor coordination but also abnormalities affecting fiber, myelin, and/or cellular integrities have been associated with schizophrenia (Keshavan et al 2002;Tkachev et al 2003;Whitford et al 2010), stress disorders (Villarreal et al 2004;Miyata et al 2011), and cocaine consumption (Ma et al 2009;Narayana et al 2009), contributing to the development of the pathological condition to a greater or lesser degree. Interestingly, in this sense, maLPA 1 -null mice have been shown to (1) develop deficits in motor impairments, which affects neuromuscular strength and the analgesic response (Santín et al 2009); (2) share anatomical, neurochemical, and behavioral abnormalities resembling those found in schizophrenia (Roberts et al 2005;Estivill-Torrús et al 2013); (3) acquire increased vulnerability to chronic stress-neural effects (CastillaOrtega et al 2011); and (4) exhibit altered conditioned responses to cocaine , suggesting the contribution of the defects described in this study to the development of these phenotypes.…”

Reduced limbic metabolism and fronto-cortical volume in rats vulnerable to alcohol addiction

“…Although similar imaging parameters have been successfully employed in rats to identify FA and WM changes induced by psychostimulant drugs (Narayana et al, 2009), additional studies using higher resolution and more isotropic voxels are warranted to provide a definite answer to this experimental question.…”

Recovering from cocaine: Insights from clinical and preclinical investigations

“…Several investigations have also documented changes in the integrity of white matter in the corpus callosum of rats exposed to chronic cocaine (Ma et al, 2009; Narayana et al, 2009). Four weeks of cocaine exposure via minipump resulted in significant changes in fractional anisotropy in the splenium of the corpus callosum, as measured with diffusion tensor imaging.…”