@article {6346,
	title = {IP3 receptor sensitization during in vivo amphetamine experience enhances NMDA receptor plasticity in dopamine neurons of the ventral tegmental area.},
	journal = {The Journal of Neuroscience: The Official Journal of the Society for Neuroscience},
	volume = {30},
	year = {2010},
	month = {2010 May 12},
	pages = {6689-99},
	abstract = {<p>Synaptic plasticity in the mesolimbic dopamine (DA) system is critically involved in reward-based conditioning and the development of drug addiction. Ca2+ signals triggered by postsynaptic action potentials (APs) drive the induction of synaptic plasticity in the CNS. However, it is not clear how AP-evoked Ca2+ signals and the resulting synaptic plasticity are altered during in vivo 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 Ca2+ signals by preceding activation of metabotropic glutamate receptors (mGluRs) generating inositol 1,4,5-trisphosphate (IP3). In this study, using brain slices prepared from male rats, we show that repeated in vivo exposure to the psychostimulant amphetamine (5 mg/kg, i.p., 3-7 d) upregulates mGluR-dependent facilitation of burst-evoked Ca2+ signals in DA neurons of the ventral tegmental area (VTA). Protein kinase A (PKA)-induced sensitization of IP3 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 Ca2+ 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.</p>
},
	keywords = {4, 5-Trisphosphate Receptors, Amphetamine, Animals, Calcium, Central Nervous System Stimulants, Classical, Conditioning, Cyclic AMP-Dependent Protein Kinases, Dopamine, Inositol 1, Isoquinolines, Long-Term Potentiation, Male, N-Methyl-D-Aspartate, Neurons, Protein Kinase Inhibitors, Rats, Receptors, Space Perception, Sprague-Dawley, Sulfonamides, Synaptic Transmission, Ventral Tegmental Area},
	issn = {1529-2401},
	doi = {10.1523/JNEUROSCI.4453-09.2010},
	author = {Ahn, Kee-Chan and Bernier, Brian E and Harnett, Mark T and Morikawa, Hitoshi}
}
