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Cholinergic control of morphine‐induced locomotion in rostromedial tegmental nucleus versus ventral tegmental area sites
Author(s) -
Wasserman David I.,
Wang Haoran G.,
Rashid Asim J.,
Josselyn Sheena A.,
Yeomans John S.
Publication year - 2013
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12279
Subject(s) - ventral tegmental area , nucleus accumbens , neuroscience , dopamine , tyrosine hydroxylase , biology , medicine , chemistry , endocrinology , dopaminergic
M5 muscarinic acetylcholine receptors expressed on ventral tegmental dopamine ( DA ) neurons are needed for opioid activation of DA outputs. Here, the M 5 receptor gene was bilaterally transfected into neurons in the ventral tegmental area ( VTA ) or the adjacent rostromedial tegmental nucleus ( RMT g) in mice by means of a H erpes simplex viral vector ( HSV ) to increase the effect of endogenous acetylcholine. Three days after HSV ‐ M 5 gene infusion in VTA sites, morphine‐induced locomotion more than doubled at two doses, while saline‐induced locomotion was unaffected. When the HSV ‐ M 5 gene was infused into the adjacent RMT g, morphine‐induced locomotion was strongly inhibited. The sharp boundary between these opposing effects was found where tyrosine hydroxylase ( TH ) and cholinesterase labelling decreases (−4.00 mm posterior to bregma). The same HSV ‐ M 5 gene transfections in M 5 knockout mice induced even stronger inhibitory behavioural effects in RMT g but more variability in VTA sites due to stereotypy. The VTA sites where HSV ‐ M 5 increased morphine‐induced locomotion receive direct inputs from many RMT g GAD ‐positive neurons, and from pontine C h AT ‐positive neurons, as shown by cholera‐toxin B retrograde tracing. Therefore, morphine‐induced locomotion was decreased by M 5 receptor gene expression in RMT g GABA neurons that directly inhibit VTA DA neurons. Conversely, enhancing M 5 receptor gene expression on VTA DA neurons increased morphine‐induced locomotion via cholinergic inputs.