Decreased firing frequency of midbrain dopamine neurons in mice lacking mu opioid receptors.
Dopamine neurons originating in the midbrain and projecting to cortico-limbic and motor structures are one of the major neuronal substrates implicated in the reinforcing properties of drugs of abuse. The output of this system is largely determined by its impulse activity (amount and pattern of firing activity). Several intrinsic and synaptic factors can influence dopamine neuronal activity and, consequently, addiction liability. Pharmacological studies indicate that mu-opioid receptors and their activation by endogenous opioids may play an important role. In the present study, we use a genetic approach to better understand the role of mu-opioid receptors in modulating dopamine neuronal activity in vivo. Using in vivo extracellular single-unit recordings, we show that mice lacking mu-opioid receptors exhibit lower firing rates of dopamine neurons compared with their wild-type littermates. Although we observed no overall changes in bursting activity compared with wild-type mice, animals lacking mu-opioid receptors exhibited a higher proportion of regular-spiking cells that lacked bursting activity. These findings are the first to emphasize the critical role of mu-opioid receptors in modulating action potential output of dopamine neurons in vivo using a genetic approach. They also provide a possible underlying mechanism for the decreased reinforcing properties of drugs of abuse that was previously observed in mice lacking mu-opioid receptors.
Mathon
Daniel S
DS
Department of Pharmacology and Anatomy, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.
Ramakers
Geert M J
GM
Pintar
John E
JE
Marinelli
Michela
M
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D003433:Crosses, Genetic; D004298:Dopamine / Q000502:physiology*; D008636:Mesencephalon / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D011930:Reaction Time; D017450:Receptors, Opioid, mu / Q000172:deficiency* / Q000235:genetics
D017450:Receptors, Opioid, mu; D004298:Dopamine