Role of Microglia in Psychostimulant Addiction



The use of psychostimulant drugs can modify brain function by inducing changes in the reward
system, mainly due to alterations in dopaminergic and glutamatergic transmissions in the mesocorticolimbic
pathway. However, the etiopathogenesis of addiction is a much more complex process.
Previous data have suggested that microglia and other immune cells are involved in events associated
with neuroplasticity and memory, which are phenomena that also occur in addiction. Nevertheless,
how dependent is the development of addiction on the activity of these cells? Although the mechanisms
are not known, some pathways may be involved. Recent data have shown psychoactive substances
may act directly on immune cells, alter their functions and induce various inflammatory mediators
that modulate synaptic activity. These could, in turn, be involved in the pathological alterations
that occur in substance use disorder. Here, we extensively review the studies demonstrating how cocaine
and amphetamines modulate microglial number, morphology, and function. We also describe the
effect of these substances in the production of inflammatory mediators and a possible involvement of
some molecular signaling pathways, such as the toll-like receptor 4. Although the literature in this
field is scarce, this review compiles the knowledge on the neuroimmune axis that is involved in the
pathogenesis of addiction, and suggests some pharmacological targets for the development of pharmacotherapy.
