Role of noradrenergic signaling by the nucleus tractus solitarius in mediating opiate reward.
Norepinephrine (NE) is widely implicated in opiate withdrawal, but much less is known about its role in opiate-induced locomotion and reward. In mice lacking dopamine beta-hydroxylase (DBH), an enzyme critical for NE synthesis, we found that NE was necessary for morphine-induced conditioned place preference (CPP; a measure of reward) and locomotion. These deficits were rescued by systemic NE restoration. Viral restoration of DBH expression in the nucleus tractus solitarius, but not in the locus coeruleus, restored CPP for morphine. Morphine-induced locomotion was partially restored by DBH expression in either brain region. These data suggest that NE signaling by the nucleus tractus solitarius is necessary for morphine reward.
Howard Hughes Medical Institute and Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Valerie G
VG
Olson
Carrie L
CL
Heusner
Ross J
RJ
Bland
Matthew J
MJ
During
David
D
Weinshenker
Richard D
RD
Palmiter
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003213:Conditioning, Psychological; D004299:Dopamine beta-Hydroxylase / Q000235:genetics / Q000378:metabolism; D015103:Droxidopa / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects; D008125:Locus Coeruleus / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000502:physiology*; D012201:Reward; D015398:Signal Transduction; D017552:Solitary Nucleus / Q000502:physiology*; D009435:Synaptic Transmission
D009020:Morphine; D004299:Dopamine beta-Hydroxylase; D015103:Droxidopa; D009638:Norepinephrine