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].