Loss of D2 Dopamine Receptor Function Modulates Cocaine-Induced Glutamatergic Synaptic Potentiation in the Ventral Tegmental Area

Madhavan, Anuradha; Argilli, Emanuela; Bonci, Antonello; Whistler, Jennifer L.

doi:10.1523/jneurosci.0809-13.2013

Cited by 25 publications

(17 citation statements)

References 41 publications

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“…Thus, in the VTA, NMDAR-mediated currents are potentiated 10–20 minutes following, but not during, D1DR activation in a PKA-dependent manner (Shilström et al, 2006). A similar effect of cocaine has recently been reported to require a downregulation in D2DR signaling (Madhavan et al, 2013). A delayed onset enhancement of NMDAR-currents by D1DRs has also been observed in the CA1 pyramidal cells of the hippocampus and was found to rely on NMDAR-independent increase in intracellular Ca 2+ (Yang, 2000).…”

Section: Cocaine Effects On Nmdar Functionsupporting

confidence: 72%

Cocaine-Induced Changes in NMDA Receptor Signaling

Ortinski

2014

Mol Neurobiol

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Addictive states are often thought to rely on lasting modification of signaling at relevant synapses. A long-standing theory posits that activity at N-methyl-D-aspartate receptors (NMDARs) is a critical component of long-term synaptic plasticity in many brain areas. Indeed, NMDAR signaling has been found to play a role in the etiology of addictive states, in particular following cocaine exposure. However, no consensus is apparent with respect to the specific effects of cocaine exposure on NMDARs. Part of the difficulty lies in the fact that NMDARs interact extensively with multiple membrane proteins and intracellular signaling cascades. This allows for highly heterogeneous patterns of NMDAR regulation by cocaine in distinct brain regions and at distinct synapses. The picture is further complicated by findings that cocaine effects on NMDARs are sensitive to the behavioral history of cocaine exposure, such as the mode of cocaine administration. This review provides a summary of evidence for cocaine-induced changes in NMDAR expression, cocaine-induced alterations in NMDAR function and cocaine effects on NMDAR control of intracellular signaling cascades.

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Section: Cocaine Effects On Nmdar Functionsupporting

confidence: 72%

Cocaine-Induced Changes in NMDA Receptor Signaling

Ortinski

2014

Mol Neurobiol

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“…Exposure to these drugs of abuse is known to induce long-term changes in the function and morphology of dopamine neurons, and these adaptive changes may contribute to the development of addiction (Luscher and Malenka, 2011, Lammel et al, 2013). While alterations in excitatory glutamatergic inputs to dopamine neurons play a central role in addiction (Saal et al, 2003, Kalivas et al, 2009), alterations in autoreceptor mediated inhibition in the VTA are also known to occur following repeated psychostimulant and alcohol exposure (Henry et al, 1989, Wolf et al, 1993, Jones et al, 2000, Marinelli et al, 2003, Perra et al, 2011, Madhavan et al, 2013). …”

Section: Plasticity and Regulation Of Autoreceptors By Rewards And Drmentioning

confidence: 99%

The role of D2-autoreceptors in regulating dopamine neuron activity and transmission

2014

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Dopamine D2-autoreceptors play a key role in regulating the activity of dopamine neurons and control the synthesis, release and uptake of dopamine. These Gi/o-coupled inhibitory receptors play a major part in shaping dopamine transmission. Found at both somatodendritic and axonal sites, autoreceptors regulate the firing patterns of dopamine neurons and control the timing and amount of dopamine released from their terminals in target regions. Alterations in the expression and activity of autoreceptors are thought to contribute to Parkinson’s disease as well as schizophrenia, drug addiction and attention deficit hyperactivity disorder (ADHD), which emphasizes the importance of D2-autoreceptors in regulating the dopamine system. This review will summarize the cellular actions of dopamine autoreceptors and discuss recent advances that have furthered our understanding of the mechanisms by which D2-receptors control dopamine transmission.

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“…Cocaine addiction is associated with enduring neurochemical differences in the brain, including glutamate (Glu) neurotransmission (for review see: Pomierny-Chamiolo et al 2014 ). In fact, in preclinical models, the expression of drug seeking, modeling the core feature of cocaine addiction, promotes Glu release in the ventral tegmental area and the core of the nucleus accumbens (Madhavan et al 2013 ). The release of Glu during cocaine seeking also elicits rapid postsynaptic changes in proteins regulating Glu signaling and surface spine morphology, while attenuation of Glu transmission reduces drug reinforcement and relapse-like behavior (McFarland et al 2003 ; Brebner et al 2005 ; Gipson et al 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Withdrawal from Cocaine Self-administration and Yoked Cocaine Delivery Dysregulates Glutamatergic mGlu5 and NMDA Receptors in the Rat Brain

et al. 2014

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In human addicts and in animal models, chronic cocaine use leads to numerous alterations in glutamatergic transmission, including its receptors. The present study focused on metabotropic glutamatergic receptors type 5 (mGluR5) and N-methyl-D-aspartate receptor subunits (NMDAR: GluN1, GluN2A, GluN2B) proteins during cocaine self-administration and after 10-day of extinction training in rats. To discriminate the contingent from the non-contingent cocaine delivery, we employed the “yoked”-triad control procedure. Protein expression in rat prefrontal cortex, nucleus accumbens, hippocampus, and dorsal striatum was determined. We also examined the Homer1b/c protein, a member of the postsynaptic density protein family that links NMDAR to mGluR5. Our results revealed that cocaine self-administration selectively increased GluN1 and GluN2A subunit in the rat hippocampus and dorsal striatum, respectively, while mGluR5 protein expression was similarly increased in the dorsal striatum of both experimental groups. Withdrawal from both contingent and non-contingent cocaine delivery induced parallel increases in prefrontal cortical GluN2A protein expression, hippocampal mGluR5, and GluN1 protein expression as well as in accumbal GluN1 subunit expression, while the mGluR5 expression was reduced in the prefrontal cortex. Extinction training in animals with a history of cocaine self-administration resulted in an elevation of the hippocampal GluN2A/GluN2B subunits and accumbal mGluR5, and in a 50 % decrease of mGluR5 protein expression in the dorsal striatum. The latter reduction was associated with Homer1b/1c protein level decrease. Our results showed that both contingent and non-contingent cocaine administration produces numerous, brain region specific, alterations in the mGluR5, NMDA, and Homer1b/1c protein expression which are dependent on the modality of cocaine administration.

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Loss of D2 Dopamine Receptor Function Modulates Cocaine-Induced Glutamatergic Synaptic Potentiation in the Ventral Tegmental Area

Cited by 25 publications

References 41 publications

Cocaine-Induced Changes in NMDA Receptor Signaling

Cocaine-Induced Changes in NMDA Receptor Signaling

The role of D2-autoreceptors in regulating dopamine neuron activity and transmission

Withdrawal from Cocaine Self-administration and Yoked Cocaine Delivery Dysregulates Glutamatergic mGlu5 and NMDA Receptors in the Rat Brain

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