title: Tegmental pedunculopontine glutamate and GABA-B synapses mediate morphine reward.
abstract: The tegmental pedunculopontine nucleus (TPP) of the midbrain is critical in mediating the acute rewarding effects of opiates. However, the circuitry and neurochemistry underlying this effect has not been determined. Here we identify TPP receptors and cell types involved in systemic morphine reward and suggest an anatomical and neurochemical model for reward in the TPP. Simple hypothetical anatomical models for serial cell arrangements and receptors in the TPP were proposed and predictions of behavioral outcome (reward or no reward) then were made, based on the administration of agonists and antagonists directly into the TPP of rats. We report that TPP-administered NMDA produced rewarding effects, although GABA agonists and antagonists had no motivational effects on their own. However, the NMDA receptor antagonist AP-7 and the GABA-B receptor antagonist saclofen, while having no motivational effects on their own, blocked systemic morphine reward as measured by conditioned place preference. These results provide positive evidence for GABA-B and glutamate synapses in the TPP, which mediates systemic morphine reward and suggest that a serial pathway for morphine reward in the TPP is unlikely.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. andrewheinmiller@hotmail.com
authors.forename: Andrew
authors.initials: A
authors.lastname: Heinmiller
authors.forename: Ryan
authors.initials: R
authors.lastname: Ting-A-Kee
authors.forename: Hector
authors.initials: H
authors.lastname: Vargas-Perez
authors.forename: Andrew
authors.initials: A
authors.lastname: Yeh
authors.forename: Derek
authors.initials: D
authors.lastname: van der Kooy
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001522:Behavior, Animal; D001640:Bicuculline / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D016202:N-Methylaspartate / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage*; D045042:Pedunculopontine Tegmental Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism*; D012201:Reward
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D018756:GABA Antagonists; D009294:Narcotics; D018080:Receptors, GABA-B; D017470:Receptors, Glutamate; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D009020:Morphine; D001418:Baclofen; C080629:saclofen; C031231:2-amino-7-phosphonoheptanoic acid; D001640:Bicuculline