TY - JOUR
T1 - Separate GABA afferents to dopamine neurons mediate acute action of opioids, development of tolerance, and expression of withdrawal
AU - Matsui, Aya
AU - Jarvie, Brooke C.
AU - Robinson, Brooks G.
AU - Hentges, Shane T.
AU - Williams, John T.
N1 - Funding Information:
The authors would like to thank Dr. C.P. Ford and members of the Williams laboratory for providing critical feedback on this manuscript. This work was supported by NIH grants, DA04523, DA34388 (J.T.W.), and DA032562 (S.T.H.).
PY - 2014/6/18
Y1 - 2014/6/18
N2 - GABA release from interneurons in VTA, projections from the nucleus accumbens (NAc), and rostromedial tegmental nucleus (RMTg) was selectively activated in rat brain slices. The inhibition induced by μ-opioid agonists was pathway dependent. Morphine induced a 46% inhibition of IPSCs evoked from the RMTg, 18% from NAc, and IPSCs evoked from VTA interneurons were almost insensitive (11% inhibition). Invivo morphine treatment resulted in tolerance to the inhibition of RMTg, but not local interneurons or NAc, inputs. One common sign of opioid withdrawal is an increase in adenosine-dependent inhibition. IPSCs evoked from the NAc were potently inhibited by activation of presynaptic adenosine receptors, whereas IPSCs evoked from RMTg were not changed. Blockade of adenosine receptors selectively increased IPSCs evoked from the NAc during morphine withdrawal. Thus, the acute action of opioids, the development of tolerance, and the expression of withdrawal are mediated by separate GABA afferents to dopamine neurons.
AB - GABA release from interneurons in VTA, projections from the nucleus accumbens (NAc), and rostromedial tegmental nucleus (RMTg) was selectively activated in rat brain slices. The inhibition induced by μ-opioid agonists was pathway dependent. Morphine induced a 46% inhibition of IPSCs evoked from the RMTg, 18% from NAc, and IPSCs evoked from VTA interneurons were almost insensitive (11% inhibition). Invivo morphine treatment resulted in tolerance to the inhibition of RMTg, but not local interneurons or NAc, inputs. One common sign of opioid withdrawal is an increase in adenosine-dependent inhibition. IPSCs evoked from the NAc were potently inhibited by activation of presynaptic adenosine receptors, whereas IPSCs evoked from RMTg were not changed. Blockade of adenosine receptors selectively increased IPSCs evoked from the NAc during morphine withdrawal. Thus, the acute action of opioids, the development of tolerance, and the expression of withdrawal are mediated by separate GABA afferents to dopamine neurons.
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U2 - 10.1016/j.neuron.2014.04.030
DO - 10.1016/j.neuron.2014.04.030
M3 - Article
C2 - 24857021
AN - SCOPUS:84902545813
SN - 0896-6273
VL - 82
SP - 1346
EP - 1356
JO - Neuron
JF - Neuron
IS - 6
ER -