{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:03:02Z","timestamp":1791216182710,"version":"4.1.0"},"reference-count":71,"publisher":"Society for Neuroscience","issue":"52","license":[{"start":{"date-parts":[[2009,6,24]],"date-time":"2009-06-24T00:00:00Z","timestamp":1245801600000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2008,12,24]]},"abstract":"<jats:p>Endocannabinoid (eCB) signaling mediates short-term and long-term synaptic depression (LTD) in many brain areas. In the ventral tegmental area (VTA) and striatum, D<jats:sub>2<\/jats:sub>dopamine receptors cooperate with group I metabotropic glutamate receptors (mGluRs) to induce eCB-mediated LTD of glutamatergic excitatory and GABAergic inhibitory (I-LTD) synaptic transmission. Because D<jats:sub>2<\/jats:sub>receptors and group I mGluR agonists are capable of inducing the release of eCBs, the predominant hypothesis is that the cooperation between these receptors to induce eCB-mediated synaptic depression results from the combined activation of type I cannabinoid (CB<jats:sub>1<\/jats:sub>) receptors by the eCBs. By determining the downstream effectors for D<jats:sub>2<\/jats:sub>receptor and group I mGluR activation in VTA dopamine neurons, we show that group I mGluR activation contributes to I-LTD induction by enhancing eCB release and CB<jats:sub>1<\/jats:sub>receptor activation. However, D<jats:sub>2<\/jats:sub>receptor activation does not enhance CB<jats:sub>1<\/jats:sub>receptor activation, but facilitates I-LTD induction via direct inhibition of cAMP-dependent protein kinase A (PKA) signaling. We further demonstrate that cAMP\/PKA signaling pathway is the downstream effector for CB<jats:sub>1<\/jats:sub>receptors and is required for eCB-mediated I-LTD induction. Our results suggest that D<jats:sub>2<\/jats:sub>receptors and CB<jats:sub>1<\/jats:sub>receptors target the same downstream effector cAMP\/PKA signaling pathway to induce I-LTD and D<jats:sub>2<\/jats:sub>receptor activation facilitates eCB-mediated I-LTD in dopamine neurons not by enhancing CB<jats:sub>1<\/jats:sub>receptor activation, but by enhancing its downstream effects.<\/jats:p>","DOI":"10.1523\/jneurosci.4035-08.2008","type":"journal-article","created":{"date-parts":[[2008,12,24]],"date-time":"2008-12-24T17:27:53Z","timestamp":1230139673000},"page":"14018-14030","source":"Crossref","is-referenced-by-count":124,"title":["D<sub>2<\/sub>Dopamine Receptor Activation Facilitates Endocannabinoid-Mediated Long-Term Synaptic Depression of GABAergic Synaptic Transmission in Midbrain Dopamine Neurons via cAMP-Protein Kinase A Signaling"],"prefix":"10.1523","volume":"28","author":[{"given":"Bin","family":"Pan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia J.","family":"Hillard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-song","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2008,12,24]]},"reference":[{"key":"2023041303354392000_28.52.14018.1","doi-asserted-by":"publisher","DOI":"10.1126\/stke.3092005pe51"},{"key":"2023041303354392000_28.52.14018.2","doi-asserted-by":"publisher","DOI":"10.1038\/385074a0"},{"key":"2023041303354392000_28.52.14018.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.05.019"},{"key":"2023041303354392000_28.52.14018.4","doi-asserted-by":"publisher","DOI":"10.1038\/366344a0"},{"key":"2023041303354392000_28.52.14018.5","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1523\/JNEUROSCI.15-02-01249.1995","article-title":"Presynaptic enhancement of inhibitory synaptic transmission by protein kinases A and C in the rat hippocampus in vitro","volume":"15","author":"Capogna","year":"1995","journal-title":"J Neurosci"},{"key":"2023041303354392000_28.52.14018.6","doi-asserted-by":"crossref","first-page":"5942","DOI":"10.1523\/JNEUROSCI.16-19-05942.1996","article-title":"Characterizing the site and mode of action of dynorphin at hippocampal mossy fiber synapses in the guinea pig","volume":"16","author":"Castillo","year":"1996","journal-title":"J Neurosci"},{"key":"2023041303354392000_28.52.14018.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(01)00299-8"},{"key":"2023041303354392000_28.52.14018.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(02)00367-6"},{"key":"2023041303354392000_28.52.14018.9","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300458"},{"key":"2023041303354392000_28.52.14018.10","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1523\/JNEUROSCI.14-01-00310.1994","article-title":"Increased transmitter release at excitatory synapses produced by direct activation of adenylate cyclase in rat hippocampal slices","volume":"14","author":"Chavez-Noriega","year":"1994","journal-title":"J Neurosci"},{"key":"2023041303354392000_28.52.14018.11","doi-asserted-by":"crossref","first-page":"8687","DOI":"10.1523\/JNEUROSCI.17-22-08687.1997","article-title":"The mechanism of cAMP-mediated enhancement at a cerebellar synapse","volume":"17","author":"Chen","year":"1997","journal-title":"J Neurosci"},{"key":"2023041303354392000_28.52.14018.12","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.29.051605.112834"},{"key":"2023041303354392000_28.52.14018.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.05.020"},{"key":"2023041303354392000_28.52.14018.14","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.37.1.205"},{"key":"2023041303354392000_28.52.14018.15","doi-asserted-by":"crossref","first-page":"8677","DOI":"10.1523\/JNEUROSCI.20-23-08677.2000","article-title":"Dopamine D3 receptors expressed by all mesencephalic dopamine neurons","volume":"20","author":"Diaz","year":"2000","journal-title":"J Neurosci"},{"key":"2023041303354392000_28.52.14018.16","doi-asserted-by":"publisher","DOI":"10.1038\/372686a0"},{"key":"2023041303354392000_28.52.14018.17","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(98)01283-1"},{"key":"2023041303354392000_28.52.14018.18","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21568"},{"key":"2023041303354392000_28.52.14018.19","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4587-05.2006"},{"key":"2023041303354392000_28.52.14018.20","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705466"},{"key":"2023041303354392000_28.52.14018.21","doi-asserted-by":"publisher","DOI":"10.1038\/7268"},{"key":"2023041303354392000_28.52.14018.22","doi-asserted-by":"publisher","DOI":"10.1159\/000140625"},{"key":"2023041303354392000_28.52.14018.23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711880105"},{"key":"2023041303354392000_28.52.14018.24","doi-asserted-by":"publisher","DOI":"10.1007\/3-540-26573-2_2"},{"key":"2023041303354392000_28.52.14018.25","doi-asserted-by":"publisher","DOI":"10.1124\/mol.61.3.578"},{"key":"2023041303354392000_28.52.14018.26","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4247-06.2007"},{"key":"2023041303354392000_28.52.14018.27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1834309100"},{"key":"2023041303354392000_28.52.14018.28","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1113\/jphysiol.1992.sp019136","article-title":"Two types of neurone in the rat ventral tegmental area and their synaptic inputs","volume":"450","author":"Johnson","year":"1992","journal-title":"J Physiol"},{"key":"2023041303354392000_28.52.14018.29","doi-asserted-by":"crossref","first-page":"9780","DOI":"10.1523\/JNEUROSCI.19-22-09780.1999","article-title":"Amphetamine depresses excitatory synaptic transmission via serotonin receptors in the ventral tegmental area","volume":"19","author":"Jones","year":"1999","journal-title":"J Neurosci"},{"key":"2023041303354392000_28.52.14018.30","doi-asserted-by":"publisher","DOI":"10.1124\/mol.105.013961"},{"key":"2023041303354392000_28.52.14018.31","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(93)90048-K"},{"key":"2023041303354392000_28.52.14018.32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.03945.x"},{"key":"2023041303354392000_28.52.14018.33","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0999-04.2004"},{"key":"2023041303354392000_28.52.14018.34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.13.7731"},{"key":"2023041303354392000_28.52.14018.35","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2959-05.2005"},{"key":"2023041303354392000_28.52.14018.36","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1113\/jphysiol.1987.sp016787","article-title":"Dopamine acts on D2 receptors to increase potassium conductance in neurones of the rat substantia nigra zona compacta","volume":"392","author":"Lacey","year":"1987","journal-title":"J Physiol"},{"key":"2023041303354392000_28.52.14018.37","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1111\/j.1476-5381.1990.tb12998.x","article-title":"Actions of cocaine on rat dopaminergic neurones in vitro","volume":"99","author":"Lacey","year":"1990","journal-title":"Br J Pharmacol"},{"key":"2023041303354392000_28.52.14018.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2005.04.022"},{"key":"2023041303354392000_28.52.14018.39","doi-asserted-by":"publisher","DOI":"10.1038\/nature04050"},{"key":"2023041303354392000_28.52.14018.40","doi-asserted-by":"publisher","DOI":"10.1038\/nn2042"},{"key":"2023041303354392000_28.52.14018.41","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00375-0"},{"key":"2023041303354392000_28.52.14018.42","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.117069"},{"key":"2023041303354392000_28.52.14018.43","doi-asserted-by":"publisher","DOI":"10.1016\/S0928-4257(97)87909-0"},{"key":"2023041303354392000_28.52.14018.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2007.04.014"},{"key":"2023041303354392000_28.52.14018.45","doi-asserted-by":"publisher","DOI":"10.1210\/me.7.2.161"},{"key":"2023041303354392000_28.52.14018.46","doi-asserted-by":"publisher","DOI":"10.1081\/RRS-200029981"},{"key":"2023041303354392000_28.52.14018.47","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5102-07.2008"},{"key":"2023041303354392000_28.52.14018.48","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.200790155"},{"key":"2023041303354392000_28.52.14018.49","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4033-07.2008"},{"key":"2023041303354392000_28.52.14018.50","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.054270"},{"key":"2023041303354392000_28.52.14018.51","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevNeurobiol.v11.i2-3.20"},{"key":"2023041303354392000_28.52.14018.52","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(98)00092-6"},{"key":"2023041303354392000_28.52.14018.53","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1247"},{"key":"2023041303354392000_28.52.14018.54","doi-asserted-by":"publisher","DOI":"10.1126\/stke.2552004pe50"},{"key":"2023041303354392000_28.52.14018.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2005.05.009"},{"key":"2023041303354392000_28.52.14018.56","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2002.02273.x"},{"key":"2023041303354392000_28.52.14018.57","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(95)00056-3"},{"key":"2023041303354392000_28.52.14018.58","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0514-07.2007"},{"key":"2023041303354392000_28.52.14018.59","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(94)90323-9"},{"key":"2023041303354392000_28.52.14018.60","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00001.2005"},{"key":"2023041303354392000_28.52.14018.61","doi-asserted-by":"publisher","DOI":"10.1124\/mol.58.2.455"},{"key":"2023041303354392000_28.52.14018.62","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0018-07.2007"},{"key":"2023041303354392000_28.52.14018.63","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2007.01.005"},{"key":"2023041303354392000_28.52.14018.64","doi-asserted-by":"publisher","DOI":"10.1038\/42015"},{"key":"2023041303354392000_28.52.14018.65","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2002.02041.x"},{"key":"2023041303354392000_28.52.14018.66","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.091843"},{"key":"2023041303354392000_28.52.14018.67","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80599-1"},{"key":"2023041303354392000_28.52.14018.68","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(91)90019-W"},{"key":"2023041303354392000_28.52.14018.69","doi-asserted-by":"publisher","DOI":"10.1111\/j.1527-3458.2007.00013.x"},{"key":"2023041303354392000_28.52.14018.70","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510797103"},{"key":"2023041303354392000_28.52.14018.71","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.00893.x"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.4035-08.2008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T19:00:52Z","timestamp":1681412452000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.4035-08.2008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,12,24]]},"references-count":71,"journal-issue":{"issue":"52","published-online":{"date-parts":[[2008,12,24]]},"published-print":{"date-parts":[[2008,12,24]]}},"alternative-id":["10.1523\/JNEUROSCI.4035-08.2008"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.4035-08.2008","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,12,24]]}}}