Opioids, such as morphine or heroin, increase forebrain dopamine (DA) release and
locomotion, and support the acquisition of conditioned place preference (CPP) or self-administration.
The most sensitive sites for these opioid effects in rodents are in the ventral tegmental
area (VTA) and rostromedial tegmental nucleus (RMTg). Opioid inhibition of GABA neurons
in these sites is hypothesized to lead to arousing and rewarding effects through disinhibition
of VTA DA neurons. We review findings that the laterodorsal tegmental (LDTg) and pedunculopontine
tegmental (PPTg) nuclei, which each contain cholinergic, GABAergic, and glutamatergic
cells, are important for these effects. LDTg and/or PPTg cholinergic inputs to VTA
mediate opioid-induced locomotion and DA activation via VTA M5 muscarinic receptors.
LDTg and/or PPTg cholinergic inputs to RMTg also modulate opioid-induced locomotion.
Lesions or inhibition of LDTg or PPTg neurons reduce morphine-induced increases in
forebrain DA release, acquisition of morphine CPP or self-administration. We propose
a circuit model that links VTA and RMTg GABA with LDTg and PPTg neurons critical for
DA-dependent opioid effects in drug-naïve rodents.