title: Muscarinic cholinergic receptor antagonists in the VTA and RMTg have opposite effects on morphine-induced locomotion in mice.
abstract: The ventral tegmental area (VTA) and the rostromedial tegmental nucleus (RMTg) each contribute to opiate reward and each receive inputs from the laterodorsal tegmental and pedunculopontine tegmental nuclei, the two principle brainstem cholinergic cell groups. We compared the contributions of VTA or RMTg muscarinic cholinergic receptors to locomotion induced by morphine infusions into the same sites. VTA co-infusion of atropine completely blocked VTA morphine-induced locomotion providing additional support for the important role of VTA muscarinic cholinergic receptors in the stimulant effects of opiates. By contrast, RMTg co-infusion of atropine increased RMTg morphine-induced locomotion. Furthermore, RMTg co-infusion of the M3-selective antagonist 4-DAMP, but not the M4-selective antagonist Tropicamide, strongly increased RMTg morphine-induced locomotion. RMTg infusions of 4-DAMP, but not of Tropicamide, by themselves strongly increased drug-free locomotion. Muscarinic cholinergic receptors in the RMTg thus also contribute to the stimulant effects of morphine, but in a way opposite to those in VTA. We suggest that the net effect of endogenous cholinergic input to the RMTg on drug-free and on RMTg morphine-induced locomotion is inhibitory.
authors.affiliation: Department of Psychology, Loyola University Chicago, 1032 West Sheridan Road, Chicago, Illinois, 60626, USA. Electronic address: ssteidl@luc.edu.
authors.forename: Stephan
authors.initials: S
authors.lastname: Steidl
authors.affiliation: Department of Psychology, Loyola University Chicago, 1032 West Sheridan Road, Chicago, Illinois, 60626, USA.
authors.forename: Ekamjeet S
authors.initials: ES
authors.lastname: Dhillon
authors.affiliation: Department of Psychology, Loyola University Chicago, 1032 West Sheridan Road, Chicago, Illinois, 60626, USA.
authors.forename: Natasha
authors.initials: N
authors.lastname: Sharma
authors.affiliation: Department of Psychology, Loyola University Chicago, 1032 West Sheridan Road, Chicago, Illinois, 60626, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Ludwig
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D001285:Atropine / Q000008:administration & dosage; D008124:Locomotion / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000008:administration & dosage*; D018727:Muscarinic Antagonists / Q000008:administration & dosage*; D010880:Piperidines / Q000008:administration & dosage; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors / Q000502:physiology*; D043588:Receptor, Muscarinic M4 / Q000037:antagonists & inhibitors / Q000502:physiology; D014331:Tropicamide / Q000008:administration & dosage; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology*
chemical_list: D018727:Muscarinic Antagonists; D010880:Piperidines; D043587:Receptor, Muscarinic M3; D043588:Receptor, Muscarinic M4; D009020:Morphine; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D014331:Tropicamide; D000109:Acetylcholine
keywords: Acetylcholine; Dopamine; Laterodorsal tegmental nucleus; Opiates; Pedunculopontine tegmental nucleus