3. Substance abuse and neuroinflammation
During the process of drug
addiction, nerve cells take an important part in brain activities,
while
abuse of drugs will alter the activities of nerve
cells[11-13]. For example, repeated delivery of
drugs triggers changes in neuronal plasticity with glutamatergic inputs
to striatal and midbrain dopamine neurons, enhances brain response to
drug cues, reduces sensitivity to non-drug
rewards,
and
increases susceptibility to stress stimuli and
irritability[14, 15].
Recently,
it has been found that almost all drug abuse can affect non-neuronal
nerve cells[16]. Non-neuronal cells constitute
most the brain cells, and they play an active role in a variety of brain
functions, including neurotransmitter release and clearance, synaptic
development and maturation, synaptic plasticity, neuronal cell survival,
immune responses et al[17]. An important goal of
drug dependence oriented research is to identify neuropharmacological
targets that contribute to the development of drug dependence drugs.
Therefore, neurobiology research
requires a better understanding of the relationship between drug abuse
and neuroinflammation[1].
Previous literature has established
that microglia and astrocytes are the most involved cells in
neuroinflammation(Figure 2)[18].
These glial cells lead to
neuroinflammation and other behaviors in addiction through the release
of interleukins[19, 20].
Of all the involved parts in the
brain, including striatum, hippocampus, hypothalamus, and prefrontal
cortex, the most studied are the striatum and
hippocampus[21-24]. An increasing amount of
evidence indicates that glial cells, such as microglia and astrocytes,
can produce interleukins. These interleukins act as neuromodulators and
modulate neuronal excitability and inhibition[25,
26], most of which modulate excitatory transmission. Interleukins
produced in microglia are key initiators of
neuroinflammation[27]. For example, IL-1β,
which is closely related to
substance abuse, is produced by the nucleotide-binding domain
leucine-rich repeat-like receptor (NLR) inflammasome, and the
macromolecular complex assembles into a caspase-1 activation platform.
The inflammasome is regulated by two signals[28,
29]. The first signal results in the induction of Il1b mRNA and its
translation into the inactive form pro-IL-1β. The second signal induces
inflammasome assembly and cleavage of pro-IL-1β by caspase-1 to active
IL-1β[30]. It enhances excitatory
neurotransmission in the hippocampus through mechanisms such as
neurotransmitter exocytosis and increased synaptic strength[31, 32].
In contrast, the production of
interleukin-17 has an inhibitory effect in the hippocampus area[33].