M5 muscarinic receptors are required for prolonged accumbal dopamine release after electrical stimulation of the pons in mice.

Midbrain dopamine neurons are activated directly by cholinergic agonists or by stimulation of the cholinergic neurons in the laterodorsal tegmental nucleus (LDT) of the pons in rats. In urethane-anesthetized mice, electrical stimulation of the LDT resulted in a rapid, stimulus-time-locked increase in dopamine release in the nucleus accumbens (NAc), followed several minutes later by a prolonged increase in dopamine release. In mutant mice with truncated M5 receptors, the prolonged phase of dopamine release was absent, but the initial, rapid phase of dopamine release was fully observed. We conclude that M5 muscarinic receptors on midbrain dopamine neurons mediate a prolonged facilitation of dopamine release in the NAc. These results imply that M5 muscarinic receptors play an important role in motivational behaviors driven by dopamine activity in the accumbens.