Chronic Treatment of Rats with SCH‐23390 or Raclopride Does Not Affect the Concentrations of DARPP‐32 or Its mRNA in Dopamine‐Innervated Brain Regions

Grebb, Jack A.; Girault, Jean‐Antoine; Ehrlich, Michelle E.; Greengard, Paul

doi:10.1111/j.1471-4159.1990.tb08839.x

Cited by 29 publications

(20 citation statements)

References 15 publications

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“…Since it was showed that DARPP-32 is downregulated in PFC of schizophrenia subjects [10,11] and that there are genetic variations associated with PFC cognitive functions [34], we did not find alterations in the expression of DARPP-32 in five brain regions, PFC, HP, ST, CX and CB, of rats after chronic treatment with typical or atypical antipsychotics. Our results of chronic treatment with typical antipsychotic was similar to that already observed in other studies with chronic treatment with haloperidol or a specific D 2 antagonist, raclopride [35,36].…”

Section: Discussionsupporting

confidence: 93%

DARPP-32 and NCS-1 Expression is not Altered in Brains of Rats Treated with Typical or Atypical Antipsychotics

et al. 2007

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Dopamine-mediated neurotransmission imbalances are associated with several psychiatry illnesses, such as schizophrenia. Recently it was demonstrated that two proteins involved in dopamine signaling are altered in prefrontal cortex (PFC) of schizophrenic patients. DARPP-32 is a key downstream effector of intracellular signaling pathway and is downregulated in PFC of schizophrenic subjects. NCS-1 is a neuronal calcium sensor that can inhibit dopamine receptor D2 internalization and is upregulated in PFC of schizophrenic subjects. It is well known that dopamine D2 receptor is the main target of antipsychotic. Therefore, our purpose was to study if chronic treatment with typical or atypical antipsychotics induced alterations in DARPP-32 and NCS-1 expression in five brain regions: prefrontal cortex, hippocampus, striatum, cortex and cerebellum. We did not find any changes in DARPP-32 and NCS-1 protein expression in any brain region investigated.

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Section: Discussionsupporting

confidence: 93%

DARPP-32 and NCS-1 Expression is not Altered in Brains of Rats Treated with Typical or Atypical Antipsychotics

et al. 2007

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“…BDNF also transiently increases phosphorylation of CREB in MSNs (Stroppolo et al, 2001), and it is possible that DARPP-32 induction by BDNF is in part dependent on Egr-1 induction by phosphorylated CREB. This process, however, must be context specific because other inducers of CREB phosphorylation, most notably dopamine and its agonists, do not alter expression of DARPP-32 in MSNs Grebb et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Egr-1 Induces DARPP-32 Expression in Striatal Medium Spiny Neurons via a Conserved Intragenic Element

et al. 2012

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DARPP-32 (dopamine and adenosine 3Ј, 5Ј-cyclic monophosphate cAMP-regulated phosphoprotein, 32 kDa) is a striatal-enriched protein that mediates signaling by dopamine and other first messengers in the medium spiny neurons. The transcriptional mechanisms that regulate striatal DARPP-32 expression remain enigmatic and are a subject of much interest in the efforts to induce a striatal phenotype in stem cells. We report the identification and characterization of a conserved region, also known as H10, in intron IV of the gene that codes for DARPP-32 (Ppp1r1b). This DNA sequence forms multiunit complexes with nuclear proteins from adult and embryonic striata of mice and rats. Purification of proteins from these complexes identified early growth response-1 (Egr-1). The interaction between Egr-1 and H10 was confirmed in vitro and in vivo by super-shift and chromatin immunoprecipitation assays, respectively. Importantly, brain-derived neurotrophic factor (BDNF), a known inducer of DARPP-32 and Egr-1 expression, enhanced Egr-1 binding to H10 in vitro. Moreover, overexpression of Egr-1 in primary striatal neurons induced the expression of DARPP-32, whereas a dominantnegative Egr-1 blocked DARPP-32 induction by BDNF. Together, this study identifies Egr-1 as a transcriptional activator of the Ppp1r1b gene and provides insight into the molecular mechanisms that regulate medium spiny neuron maturation.

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“…This is particularly true in the case of dopamine antagonist therapy, in which side effects and drug efficacy are often manifest after long-term receptor blockade. There have been a number of studies evaluating the effects of chronic exposure to selective antagonists, however these studies have largely focused on contrasting the effects of D1 or D2 selective antagonists administered independently (Duffy et al, 1992;Vaccheri et al, 1987;Esposito and Bunney, 1989;Lublin et al, 1993;LaHoste and Marshall, 1991;Grebb et al, 1990). Only a limited number of studies have examined the chronic effects of D1 and D2 antagonists administered in combination (Schettini et al, 1992;Hess et al, 1988;, and there has been, to date, no systematic investigation of all of the potential interactions between dopamine receptor subtypes which could accompany chronic drug exposure.…”

Section: Introductionmentioning

confidence: 96%

Interactions between D1 and D2 dopamine receptor family agonists and antagonists: the effects of chronic exposure on behavior and receptor binding in rats and their clinical implications

Braun

Laruelle

Mouradian

1997

J. Neural Transmission

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Functional interactions between dopamine receptor subtypes may affect behavioral and biochemical responses which serve as models for neuropsychiatric illnesses and the clinical effects of drug therapy. We evaluated the effects of chronic exposure to the selective D1 receptor antagonist SCH 23390, and the selective D2 receptor antagonist metoclopramide, on spontaneous and drug-induced behavior and receptor density in rats, and then determined how these effects would be modified by concurrent administration of antagonists or agonists [SKF 38393, LY 171555 (quinpirole)] selective for the complementary receptor subtype. Administered alone, both the D1 and D2 antagonists had acute cataleptic effects to which animals became tolerant following chronic treatment, but the selective antagonists had opposing effects on spontaneous locomotor activity. Both antagonists produced equivalent, supersensitive behavioral responses to apomorphine, and resulted in an increase in D2 receptor density. Coadministration of the D1 and D2 antagonists had a synergistic effect on catalepsy, attenuated the effects on spontaneous locomotor activity observed with either drug alone, and had an additive effect on both apomorphine-induced stereotypic behavior and D2 receptor proliferation. On the other hand, when either selective antagonist was combined with the agonist selective for the complementary receptor subtype, both D2 receptor proliferation and behavioral supersensitivity were completely blocked. Combined antagonist-agonist treatments had opposing effects on the development of tolerance to antagonist-induced catalepsy. D2 - but not D1 - receptor densities were correlated with animals' behavioral responses to apomorphine. There results support and extend the notion that complex functional interactions between D1 and D2 receptor families occur within the central nervous system, and suggest that novel effects might be derived from combined administration of receptor selective agonists and antagonists.

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Chronic Treatment of Rats with SCH‐23390 or Raclopride Does Not Affect the Concentrations of DARPP‐32 or Its mRNA in Dopamine‐Innervated Brain Regions

Cited by 29 publications

References 15 publications

DARPP-32 and NCS-1 Expression is not Altered in Brains of Rats Treated with Typical or Atypical Antipsychotics

DARPP-32 and NCS-1 Expression is not Altered in Brains of Rats Treated with Typical or Atypical Antipsychotics

Egr-1 Induces DARPP-32 Expression in Striatal Medium Spiny Neurons via a Conserved Intragenic Element

Interactions between D1 and D2 dopamine receptor family agonists and antagonists: the effects of chronic exposure on behavior and receptor binding in rats and their clinical implications

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