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).