Cholesterol is indispensable for neuronal functioning, synaptic plasticity and CNS myelination [31]–[32]. Functionally, this may also relate to the decreased frontal white matter volume observed in drug abusers [33]. Normal white matter maturation appears to be arrested in the frontal and temporal lobes in cocaine abusers [34]. Microarray studies have demonstrated changes in myelin transcripts in the nucleus accumbens and prefrontal cortex of cocaine abusers [14], [16]. This is reminiscent of the situation in the prefrontal cortex in schizophrenia, where expression of APOL1, 2 and 4 transcripts were increased [35], and myelin transcripts were decreased [9]. Importantly, changes in these primate-specific lipid metabolism genes underscore inherent differences between non-primate models and human drug abuse at a cellular level, and highlight the importance of studies in human postmortem brain.
