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Addictive drugs hijack mechanisms of learning and memory that normally underlie reinforcement of natural rewards and induce synaptic plasticity of glutamatergic transmission in the mesolimbic dopamine (DA) system. In the ventral tegmental area (VTA), a single exposure to cocaine efficiently triggers NMDA receptor-dependent synaptic plasticity in DA neurons,(More)
The activation of metabotropic glutamate receptors (mGluRs) leads to long-term depression (mGluR-LTD) at many synapses of the brain. The induction of mGluR-LTD is well characterized, whereas the mechanisms underlying its expression remain largely elusive. mGluR-LTD in the ventral tegmental area (VTA) efficiently reverses cocaine-induced strengthening of(More)
Cocaine strengthens excitatory synapses onto midbrain dopamine neurons through the synaptic delivery of GluR1-containing AMPA receptors. This cocaine-evoked plasticity depends on NMDA receptor activation, but its behavioral significance in the context of addiction remains elusive. Here, we generated mice lacking the GluR1, GluR2, or NR1 receptor subunits(More)
The manner in which drug-evoked synaptic plasticity affects reward circuits remains largely elusive. We found that cocaine reduced NMDA receptor excitatory postsynaptic currents and inserted GluA2-lacking AMPA receptors in dopamine neurons of mice. Consequently, a stimulation protocol pairing glutamate release with hyperpolarizing current injections further(More)
Drug-evoked synaptic plasticity in the mesolimbic dopamine (DA) system reorganizes neural circuits that may lead to addictive behavior. The first cocaine exposure potentiates AMPAR excitatory postsynaptic currents (EPSCs) onto DA neurons of the VTA but reduces the amplitude of NMDAR-EPSCs. While plasticity of AMPAR transmission is expressed by insertion of(More)
The firing of mesolimbic dopamine neurons is important for drug-induced reinforcement, although underlying genetic factors remain poorly understood. In a recent genome-wide association metaanalysis of alcohol intake, we identified a suggestive association of SNP rs26907 in the ras-specific guanine-nucleotide releasing factor 2 (RASGRF2) gene, encoding a(More)
Addictive substances mediate positive and negative states promoting persistent drug use. However, substrates for aversive effects of drugs remain elusive. We found that, in mouse lateral habenula (LHb) neurons targeting the rostromedial tegmental nucleus, cocaine enhanced glutamatergic transmission, reduced K(+) currents and increased excitability. GluA1(More)
Maternal exposure to cocaine may perturb fetal development and affect synaptic maturation in the offspring. However, the molecular mechanism underlying such changes remains elusive. We focused on the postnatal maturation of glutamatergic transmission onto ventral tegmental area dopamine neurons in the mouse. We found that, during the first postnatal week,(More)
BACKGROUND Addictive drugs have in common that they cause surges in dopamine (DA) concentration in the mesolimbic reward system and elicit synaptic plasticity in DA neurons of the ventral tegmental area (VTA). Cocaine for example drives insertion of GluA2-lacking AMPA receptors (AMPARs) at glutamatergic synapes in DA neurons. However it remains elusive(More)
The lateral habenula (LHb) is an epithalamic region with a crucial role in the regulation of midbrain monoaminergic systems. Over the past few years a renewed interest in the LHb has emerged due to studies highlighting its central role in encoding rewarding and aversive aspects of stimuli. Moreover, an increasing number of functional as well as behavioral(More)