{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:10:07Z","timestamp":1785471007325,"version":"3.56.0"},"reference-count":66,"publisher":"Society for Neuroscience","issue":"19","license":[{"start":{"date-parts":[[2010,11,12]],"date-time":"2010-11-12T00:00:00Z","timestamp":1289520000000},"content-version":"vor","delay-in-days":184,"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":[[2010,5,12]]},"abstract":"<jats:p>Synaptic plasticity in the mesolimbic dopamine (DA) system is critically involved in reward-based conditioning and the development of drug addiction. Ca<jats:sup>2+<\/jats:sup>signals triggered by postsynaptic action potentials (APs) drive the induction of synaptic plasticity in the CNS. However, it is not clear how AP-evoked Ca<jats:sup>2+<\/jats:sup>signals and the resulting synaptic plasticity are altered during<jats:italic>in vivo<\/jats:italic>exposure to drugs of abuse. We have recently described long-term potentiation (LTP) of NMDA receptor (NMDAR)-mediated transmission onto DA neurons that is induced in a manner dependent on bursts of APs. LTP induction requires amplification of burst-evoked Ca<jats:sup>2+<\/jats:sup>signals by preceding activation of metabotropic glutamate receptors (mGluRs) generating inositol 1,4,5-trisphosphate (IP<jats:sub>3<\/jats:sub>). In this study, using brain slices prepared from male rats, we show that repeated<jats:italic>in vivo<\/jats:italic>exposure to the psychostimulant amphetamine (5 mg\/kg, i.p., 3\u20137 d) upregulates mGluR-dependent facilitation of burst-evoked Ca<jats:sup>2+<\/jats:sup>signals in DA neurons of the ventral tegmental area (VTA). Protein kinase A (PKA)-induced sensitization of IP<jats:sub>3<\/jats:sub>receptors mediates this upregulation of mGluR action. As a consequence, NMDAR-mediated transmission becomes more susceptible to LTP induction after repeated amphetamine exposure. We have also found that the magnitude of amphetamine-conditioned place preference (CPP) in behaving rats correlates with the magnitude of mGluR-dependent Ca<jats:sup>2+<\/jats:sup>signal facilitation measured in VTA slices prepared from these rats. Furthermore, the development of amphetamine CPP is significantly attenuated by intra-VTA infusion of the PKA inhibitor H89. We propose that enhancement of mGluR-dependent NMDAR plasticity in the VTA may promote the learning of environmental stimuli repeatedly associated with amphetamine experience.<\/jats:p>","DOI":"10.1523\/jneurosci.4453-09.2010","type":"journal-article","created":{"date-parts":[[2010,5,12]],"date-time":"2010-05-12T17:43:42Z","timestamp":1273686222000},"page":"6689-6699","source":"Crossref","is-referenced-by-count":36,"title":["IP<sub>3<\/sub>Receptor Sensitization during<i>In Vivo<\/i>Amphetamine Experience Enhances NMDA Receptor Plasticity in Dopamine Neurons of the Ventral Tegmental Area"],"prefix":"10.1523","volume":"30","author":[{"given":"Kee-Chan","family":"Ahn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian E.","family":"Bernier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark T.","family":"Harnett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Morikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2010,5,12]]},"reference":[{"key":"2023041303441709000_30.19.6689.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2356"},{"key":"2023041303441709000_30.19.6689.2","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2008.117"},{"key":"2023041303441709000_30.19.6689.3","doi-asserted-by":"publisher","DOI":"10.1038\/nn1682"},{"key":"2023041303441709000_30.19.6689.4","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-006-0578-x"},{"key":"2023041303441709000_30.19.6689.5","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1523\/JNEUROSCI.17-02-00796.1997","article-title":"Increased probability of GABA release during withdrawal from morphine","volume":"17","author":"Bonci","year":"1997","journal-title":"J Neurosci"},{"key":"2023041303441709000_30.19.6689.6","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1312-04.2004"},{"key":"2023041303441709000_30.19.6689.7","doi-asserted-by":"crossref","first-page":"10502","DOI":"10.1523\/JNEUROSCI.19-23-10502.1999","article-title":"How the basal ganglia use parallel excitatory and inhibitory learning pathways to selectively respond to unexpected rewarding cues","volume":"19","author":"Brown","year":"1999","journal-title":"J Neurosci"},{"key":"2023041303441709000_30.19.6689.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0741-8329(96)00069-9"},{"key":"2023041303441709000_30.19.6689.9","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(99)00746-3"},{"key":"2023041303441709000_30.19.6689.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2007.05.018"},{"key":"2023041303441709000_30.19.6689.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.05.024"},{"key":"2023041303441709000_30.19.6689.12","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0139-07.2007"},{"key":"2023041303441709000_30.19.6689.13","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-003-1559-y"},{"key":"2023041303441709000_30.19.6689.14","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4053-09.2009"},{"key":"2023041303441709000_30.19.6689.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.07.010"},{"key":"2023041303441709000_30.19.6689.16","doi-asserted-by":"publisher","DOI":"10.1038\/nn1579"},{"key":"2023041303441709000_30.19.6689.17","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300495"},{"key":"2023041303441709000_30.19.6689.18","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4331-05.2006"},{"key":"2023041303441709000_30.19.6689.19","doi-asserted-by":"crossref","first-page":"6362","DOI":"10.1523\/JNEUROSCI.21-16-06362.2001","article-title":"Amphetamine-induced plasticity of AMPA receptors in the ventral tegmental area: effects on extracellular levels of dopamine and glutamate in freely moving rats","volume":"21","author":"Giorgetti","year":"2001","journal-title":"J Neurosci"},{"key":"2023041303441709000_30.19.6689.20","doi-asserted-by":"publisher","DOI":"10.1038\/35084134"},{"key":"2023041303441709000_30.19.6689.21","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1152\/jn.1999.82.4.1974","article-title":"Group I metabotropic glutamate receptors mediate an inward current in rat substantia nigra dopamine neurons that is independent from calcium mobilization","volume":"82","author":"Guatteo","year":"1999","journal-title":"J Neurophysiol"},{"key":"2023041303441709000_30.19.6689.22","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2519-09.2009"},{"key":"2023041303441709000_30.19.6689.23","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1097\/00008877-199807000-00001","article-title":"Enhanced appetitive conditioning following repeated pretreatment with D-amphetamine","volume":"9","author":"Harmer","year":"1998","journal-title":"Behav Pharmacol"},{"key":"2023041303441709000_30.19.6689.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.05.011"},{"key":"2023041303441709000_30.19.6689.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.09.018"},{"key":"2023041303441709000_30.19.6689.26","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.29.051605.113009"},{"key":"2023041303441709000_30.19.6689.27","doi-asserted-by":"publisher","DOI":"10.1126\/science.1329209"},{"key":"2023041303441709000_30.19.6689.28","doi-asserted-by":"crossref","first-page":"5575","DOI":"10.1523\/JNEUROSCI.20-15-05575.2000","article-title":"Amphetamine blocks long-term synaptic depression in the ventral tegmental area","volume":"20","author":"Jones","year":"2000","journal-title":"J Neurosci"},{"key":"2023041303441709000_30.19.6689.29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401373101"},{"key":"2023041303441709000_30.19.6689.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.lmot.2006.07.004"},{"key":"2023041303441709000_30.19.6689.31","doi-asserted-by":"publisher","DOI":"10.1007\/BF00451687"},{"key":"2023041303441709000_30.19.6689.32","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2367"},{"key":"2023041303441709000_30.19.6689.33","doi-asserted-by":"publisher","DOI":"10.1038\/nature08028"},{"key":"2023041303441709000_30.19.6689.34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.77.12.7237"},{"key":"2023041303441709000_30.19.6689.35","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1523\/JNEUROSCI.22-06-02074.2002","article-title":"Long-lasting potentiation of GABAergic synapses in dopamine neurons after a single in vivo ethanol exposure","volume":"22","author":"Melis","year":"2002","journal-title":"J Neurosci"},{"key":"2023041303441709000_30.19.6689.36","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/j.1476-5381.1989.tb16872.x","article-title":"The mechanism of amphetamine-induced inhibition of rat substantia nigra compacta neurones investigated with intracellular recording in vitro","volume":"98","author":"Mercuri","year":"1989","journal-title":"Br J Pharmacol"},{"key":"2023041303441709000_30.19.6689.37","doi-asserted-by":"publisher","DOI":"10.1142\/S0219635208001782"},{"key":"2023041303441709000_30.19.6689.38","first-page":"RC103","article-title":"Inositol 1,4,5-triphosphate-evoked responses in midbrain dopamine neurons","volume-title":"J Neurosci","volume":"20","author":"Morikawa","year":"2000"},{"key":"2023041303441709000_30.19.6689.39","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1042\/bj2770125","article-title":"Involvement of the C-terminus of the inositol 1,4,5-trisphosphate receptor in Ca2+ release analysed using region-specific monoclonal antibodies","volume":"277","author":"Nakade","year":"1991","journal-title":"Biochem J"},{"key":"2023041303441709000_30.19.6689.40","doi-asserted-by":"publisher","DOI":"10.1007\/s004410050641"},{"key":"2023041303441709000_30.19.6689.41","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5335.58"},{"key":"2023041303441709000_30.19.6689.42","doi-asserted-by":"publisher","DOI":"10.1124\/mol.54.2.419"},{"key":"2023041303441709000_30.19.6689.43","doi-asserted-by":"publisher","DOI":"10.1002\/syn.890100208"},{"key":"2023041303441709000_30.19.6689.44","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1478-05.2005"},{"key":"2023041303441709000_30.19.6689.45","unstructured":"Paxinos G Watson C (1998) The rat brain in stereotaxic coordinates (Academic, San Diego), Ed 4."},{"key":"2023041303441709000_30.19.6689.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.01.027"},{"key":"2023041303441709000_30.19.6689.47","doi-asserted-by":"publisher","DOI":"10.1038\/nn1687"},{"key":"2023041303441709000_30.19.6689.48","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4341-06.2007"},{"key":"2023041303441709000_30.19.6689.49","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.neuron.2007.12.029","article-title":"CRF facilitates calcium release from intracellular stores in midbrain dopamine neurons","volume":"57","author":"Riegel","year":"2008","journal-title":"Neuron"},{"key":"2023041303441709000_30.19.6689.50","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00021-7"},{"key":"2023041303441709000_30.19.6689.51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/jn.1998.80.1.1","article-title":"Predictive reward signal of dopamine neurons","volume":"80","author":"Schultz","year":"1998","journal-title":"J Neurophysiol"},{"key":"2023041303441709000_30.19.6689.52","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(95)00852-7"},{"key":"2023041303441709000_30.19.6689.53","doi-asserted-by":"publisher","DOI":"10.1126\/science.1160873"},{"key":"2023041303441709000_30.19.6689.54","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1523\/JNEUROSCI.23-02-00403.2003","article-title":"Modulation of type 1 inositol (1,4,5)-trisphosphate receptor function by protein kinase a and protein phosphatase 1\u03b1","volume":"23","author":"Tang","year":"2003","journal-title":"J Neurosci"},{"key":"2023041303441709000_30.19.6689.55","doi-asserted-by":"publisher","DOI":"10.1016\/S0143416002001859"},{"key":"2023041303441709000_30.19.6689.56","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S0022-3565(24)38104-2","article-title":"Necessary role for ventral tegmental area adenylate cyclase and protein kinase A in induction of behavioral sensitization to intraventral tegmental area amphetamine","volume":"289","author":"Tolliver","year":"1999","journal-title":"J Pharmacol Exp Ther"},{"key":"2023041303441709000_30.19.6689.57","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(98)00060-4"},{"key":"2023041303441709000_30.19.6689.58","doi-asserted-by":"publisher","DOI":"10.1038\/35079077"},{"key":"2023041303441709000_30.19.6689.59","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.152314"},{"key":"2023041303441709000_30.19.6689.60","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.150078"},{"key":"2023041303441709000_30.19.6689.61"},{"key":"2023041303441709000_30.19.6689.62","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1406"},{"key":"2023041303441709000_30.19.6689.63","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2004.07.006"},{"key":"2023041303441709000_30.19.6689.64","doi-asserted-by":"crossref","first-page":"3443","DOI":"10.1523\/JNEUROSCI.21-10-03443.2001","article-title":"Differential expression of the small-conductance, calcium-activated potassium channel SK3 is critical for pacemaker control in dopaminergic midbrain neurons","volume":"21","author":"Wolfart","year":"2001","journal-title":"J Neurosci"},{"key":"2023041303441709000_30.19.6689.65","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)90087-4"},{"key":"2023041303441709000_30.19.6689.66","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0813415106"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.4453-09.2010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T20:47:16Z","timestamp":1740084436000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.4453-09.2010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,5,12]]},"references-count":66,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2010,5,12]]},"published-print":{"date-parts":[[2010,5,12]]}},"alternative-id":["10.1523\/JNEUROSCI.4453-09.2010"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.4453-09.2010","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,5,12]]}}}