Regulators of G Protein Signaling: Rapid Changes in mRNA Abundance in Response to Amphetamine

Burchett, Scott A.; Volk, Michael L.; Bannon, Michael J.; Granneman, James G.

doi:10.1046/j.1471-4159.1998.70052216.x

Cited by 101 publications

(79 citation statements)

References 15 publications

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“…We have found that rats exposed to PCP show attenuated D 4 inhibition of NMDAR current as a result of the loss of D 4 regulation of Ca 2ϩ /camodulin-dependent protein kinase II and unchanged D 1 enhancement of NMDAR current (Wang et al, 2006). Levels of RGS proteins or mRNAs are tightly regulated by neuronal stimuli, which provides an important mechanism for influencing GPCR signaling pathways (Burchett et al, 1998;Ingi et al, 1998). The specific alteration of RGS4 expression in PFC, a prominent area affected in schizophrenia (Weinberger et al, 1986;Andreasen et al, 1997), hints that RGS4 in PFC neurons may have specialized roles in schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

RGS4 Modulates Serotonin Signaling in Prefrontal Cortex and Links to Serotonin Dysfunction in a Rat Model of Schizophrenia

Jiang²,

Yan³

2007

Molecular Pharmacology

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Regulator of G protein signaling 4 (RGS4) has recently been identified as one of the genes linked to the susceptibility of schizophrenia. However, the functional roles of RGS4 and how it may be involved in the pathophysiology of schizophrenia remain largely unknown. In this study, we investigated the possible impact of RGS4 on the function of serotonin and dopamine receptors, two main targets for schizophrenia treatment. Activation of serotonin 5-HT 1A receptors or dopamine D 4 receptors down-regulates the function of NMDA receptor (NMDAR) channel, a key player controlling cognition and emotion, in pyramidal neurons of prefrontal cortex (PFC). Blocking RGS4 function significantly potentiated the 5-HT 1A regulation of NMDAR current; conversely, overexpression of RGS4 attenuated the 5-HT 1A effect. In contrast, the D 4 regulation of NMDAR current was not altered by RGS4 manipulation. Moreover, the 5-HT 1A regulation of NMDA receptors was significantly enhanced in a subset of PFC pyramidal neurons from rats treated with subchronic phencyclidine, an animal model of schizophrenia, which was found to be associated with specifically decreased RGS4 expression in these cells. Thus, our study has revealed an important coupling of RGS4 to serotonin signaling in cortical neurons and provided a molecular and cellular mechanism underlying the potential involvement of RGS4 in the pathophysiology of schizophrenia.

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Section: Discussionmentioning

confidence: 99%

RGS4 Modulates Serotonin Signaling in Prefrontal Cortex and Links to Serotonin Dysfunction in a Rat Model of Schizophrenia

Jiang²,

Yan³

2007

Molecular Pharmacology

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“…In the current study, we found a significant increase in the midbrain RGS2 and RGS4 mRNA levels 18 h following 5 days of AMPH self-administration. Reports on RGS2 mRNA levels following non-contingent AMPH treatment have not been consistent with no change (Burchett et al, 1998) and an increase (Seeman et al, 2007) owing to different lengths of AMPH treatment and withdrawal. These data suggest that AMPH modulates RGS2 mRNA levels in a brain region-dependent manner.…”

Section: Amph Self-administration Selectively Promoted Membrane Transmentioning

confidence: 93%

Amphetamine Self-Administration Attenuates Dopamine D2 Autoreceptor Function

Calipari

Sun

Eldeeb

et al. 2014

Neuropsychopharmacol

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Dopamine D2 autoreceptors located on the midbrain dopaminergic neurons modulate dopamine (DA) neuron firing, DA release, and DA synthesis through a negative-feedback mechanism. Dysfunctional D2 autoreceptors following repeated drug exposure could lead to aberrant DA activity in the ventral tegmental area (VTA) and projection areas such as nucleus accumbens (NAcc), promoting drugseeking and -taking behavior. Therefore, it is important to understand molecular mechanisms underlying drug-induced changes in D2 autoreceptors. Here, we reported that 5 days of amphetamine (AMPH) self-administration reduced the ability of D2 autoreceptors to inhibit DA release in the NAcc as determined by voltammetry. Using the antibody-capture [ 35 S]GTPgS scintillation proximity assay, we demonstrated for the first time that midbrain D2/D3 receptors were preferentially coupled to Gai2, whereas striatal D2/D3 receptors were coupled equally to Gai2 and Gao for signaling. Importantly, AMPH abolished the interaction between Gai2 and D2/D3 receptors in the midbrain while leaving striatal D2/D3 receptors unchanged. The disruption of the coupling between D2/D3 receptors and Gai2 by AMPH is at least partially explained by the enhanced RGS2 (regulator of G-protein signaling 2) activity resulting from an increased RGS2 trafficking to the membrane. AMPH had no effects on the midbrain expression and trafficking of other RGS proteins such as RGS4 and RGS8. Our data suggest that midbrain D2/D3 receptors are more susceptible to AMPH-induced alterations. Reduced D2 autoreceptor function could lead to enhanced DA signaling and ultimately addiction-related behavior. RGS2 may be a potential non-dopaminergic target for pharmacological intervention of dysfunctional DA transmission and drug addiction.

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“…It shows morphine-insensitive upregulation in a model of neuropathic pain (Garnier et al, 2003) and is reduced in schizophrenia (Mirnics et al, 2001). The acute or repeated administration of amphetamine promotes selective changes in striatal RGS-R4 mRNA levels (Burchett et al, 1998(Burchett et al, , 1999. Agonists and antagonists at D1 and D2 dopamine receptors also bring about changes in the level of this RGS4 mRNA (Robinet et al, 2001a, b;Geurts et al, 2002;Taymans et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Expression of Neural RGS-R7 and Gβ5 Proteins in Response to Acute and Chronic Morphine

López-Fando

Rodríguez-Muñoz

Sánchez‐Blázquez

et al. 2004

Neuropsychopharmacol

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The R7 subfamily of regulators of G-protein signaling (RGS) proteins (RGS6, RGS7, RGS9-2, and RGS11), and its binding protein Gb5, are found in neural structures of mouse brain. A single intracerebroventricular priming dose of 10 nmol morphine gave rise to acute tolerance to the analgesic effects of successive identical test doses of the opioid. At 2 h after administering the acute opioid, RGS7 mRNA levels in the striatum plus those of RGS9-2 in the striatum and thalamus were increased, whereas RGS9-2 and RGS11 mRNA were reduced in the cortex. Similar but attenuated RGS-R7 mRNA changes persisted 24 h after acute morphine administration. No changes in Gb5 mRNA levels were observed. At 2 days after commencing sustained morphine treatment, the levels of mRNA for RGS7, RGS9-2, RGS11, and Gb5 increased in most of the brain structures studied (striatum, thalamus, periaqueductal gray matter (PAG), and cortex). In these morphine tolerant-dependent mice, the greater changes were found for RGS9-2 in the thalamus (4500%) and PAG (4200%). In post-dependent mice, the increases in RGS-R7 and Gb5 mRNA still persisted in the PAG and striatum at 8 and 16 days after starting the chronic opioid treatment. The raised mRNA levels promoted by chronic, but not by acute, morphine, were accompanied by increases in the encoded proteins. This is probably a result of the costabilization of the RGS-R7 and Gb5 proteins forming heterodimers. Opioidinduced adaptations of RGS-R7 and Gb5 genes may regulate the severity of morphine-induced tolerance/dependence and the duration of the post-dependent period, helping to recover the normal response.

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Regulators of G Protein Signaling: Rapid Changes in mRNA Abundance in Response to Amphetamine

Cited by 101 publications

References 15 publications

RGS4 Modulates Serotonin Signaling in Prefrontal Cortex and Links to Serotonin Dysfunction in a Rat Model of Schizophrenia

RGS4 Modulates Serotonin Signaling in Prefrontal Cortex and Links to Serotonin Dysfunction in a Rat Model of Schizophrenia

Amphetamine Self-Administration Attenuates Dopamine D2 Autoreceptor Function

Expression of Neural RGS-R7 and Gβ5 Proteins in Response to Acute and Chronic Morphine

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