7. Modulation of dopamine transmission by opioid receptors
Opioids regulate neurotransmission in many brain regions by acting on three types of receptors: delta opioid receptors (DOR), kappa opioid receptors (KOR), and mu opioid receptors (MOR) (Reeves et al., 2022; Stein, 2016). Opioid receptors in the CNS are activated by endogenous opioid peptides including enkephalin (MOR and DOR) and dynorphin (KOR). SPNs throughout the striatum produce opioid peptides, and opioid receptors are expressed on a variety of striatal neurons and afferents. The expression patterns of opioid peptides and their receptors facilitate substantial interaction between the opioidergic and dopaminergic systems (reviewed in Sgroi & Tonini, 2018). All three types of opioid receptors are Gαi/o-coupled and when expressed at presynaptic sites, their activation can inhibit dopamine release via activation of GIRK channels and inhibition of voltage-gated Ca2+ channels. Activation of presynaptic opioid receptors can induce both acute and long-term depression of synaptic transmission, depending on the synapse (Atwood et al., 2014; Atwood et al., 2014). Opioid receptors can modulate dopamine transmission by modulating several aspects of circuitry controlling dopamine release, including presynaptic inhibition of dopamine terminals, regulation of CIN excitability, presynaptic inhibition of glutamatergic inputs to the striatum, and inhibition of GABA transmission in the midbrain to disinhibit dopamine neurons (reviewed in Darcq & Kieffer, 2018).