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Opioid-induced rewards, locomotion, and dopamine activation: A proposed model for control by mesopontine and rostromedial tegmental neurons.

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      Abstract

      Opioids, such as morphine or heroin, increase forebrain dopamine (DA) release and locomotion, and support the acquisition of conditioned place preference (CPP) or self-administration. The most sensitive sites for these opioid effects in rodents are in the ventral tegmental area (VTA) and rostromedial tegmental nucleus (RMTg). Opioid inhibition of GABA neurons in these sites is hypothesized to lead to arousing and rewarding effects through disinhibition of VTA DA neurons. We review findings that the laterodorsal tegmental (LDTg) and pedunculopontine tegmental (PPTg) nuclei, which each contain cholinergic, GABAergic, and glutamatergic cells, are important for these effects. LDTg and/or PPTg cholinergic inputs to VTA mediate opioid-induced locomotion and DA activation via VTA M5 muscarinic receptors. LDTg and/or PPTg cholinergic inputs to RMTg also modulate opioid-induced locomotion. Lesions or inhibition of LDTg or PPTg neurons reduce morphine-induced increases in forebrain DA release, acquisition of morphine CPP or self-administration. We propose a circuit model that links VTA and RMTg GABA with LDTg and PPTg neurons critical for DA-dependent opioid effects in drug-naïve rodents.

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      Affiliations
      [1 ] Dept of Psychology, Loyola University Chicago, United States. Electronic address: ssteidl@luc.edu.
      [2 ] Robarts Research Institute, University of Western Ontario, Canada.
      [3 ] Dept of Neurologic Surgery, Mayo Clinic, United States.
      [4 ] Dept of Psychology, University of Toronto, Canada.
      Journal
      Neurosci Biobehav Rev
      Neuroscience and biobehavioral reviews
      Elsevier BV
      1873-7528
      0149-7634
      Dec 2017
      : 83
      28951251 S0149-7634(17)30444-X 10.1016/j.neubiorev.2017.09.022 5730464 NIHMS912514

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