Chronic Haloperidol Promotes Corticostriatal Long-Term Potentiation by Targeting Dopamine D2L Receptors

Centonze, Diego; Usiello, Alessandro; Costa, Cinzia; Picconi, Barbara; Erbs, Eric; Bernardi, Giorgio; Borrelli, Emiliana; Calabresi, Paolo

doi:10.1523/jneurosci.1274-04.2004

Cited by 91 publications

(67 citation statements)

References 75 publications

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“…This finding confirms a specific neurocomputational prediction that postsynaptic striatal D2 receptors are critical for integrating and learning from low DA levels during negative outcomes (4,6,7). Neural evidence for this claim comes from studies showing that postsynaptic D2 receptor blockade (simulating the lack of DA during dips) enhances corticostriatal long-term potentiation (39), associated with NoGo learning in the models (6). Nevertheless, this claim is controversial.…”

Section: Discussionsupporting

confidence: 65%

Genetic triple dissociation reveals multiple roles for dopamine in reinforcement learning

Frank

Moustafa²,

Haughey³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

632

836

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What are the genetic and neural components that support adaptive learning from positive and negative outcomes? Here, we show with genetic analyses that three independent dopaminergic mechanisms contribute to reward and avoidance learning in humans. A polymorphism in the DARPP-32 gene, associated with striatal dopamine function, predicted relatively better probabilistic reward learning. Conversely, the C957T polymorphism of the DRD2 gene, associated with striatal D2 receptor function, predicted the degree to which participants learned to avoid choices that had been probabilistically associated with negative outcomes. The Val/Met polymorphism of the COMT gene, associated with prefrontal cortical dopamine function, predicted participants' ability to rapidly adapt behavior on a trial-to-trial basis. These findings support a neurocomputational dissociation between striatal and prefrontal dopaminergic mechanisms in reinforcement learning. Computational maximum likelihood analyses reveal independent gene effects on three reinforcement learning parameters that can explain the observed dissociations.basal ganglia ͉ prefrontal cortex ͉ computational model

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Section: Discussionsupporting

confidence: 65%

Genetic triple dissociation reveals multiple roles for dopamine in reinforcement learning

Frank

Moustafa²,

Haughey³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

632

836

View full text Add to dashboard Cite

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“…Striatal cells were silent at rest and showed membrane rectification and tonic firing activity during depolarizing current pulses. These features closely resembled the electrical activity described previously for mouse spiny neurons (Centonze et al, 2004a). We focused our attention on the potential effect of D-aspartate on corticostriatal LTD, because this form of synaptic plasticity is blocked after enhancement of NMDAR signaling (Calabresi et al, 1992), as well as in response to antipsychotic treatment with haloperidol (Centonze et al, 2004a).…”

Section: Altered Corticostriatal Synaptic Transmission and Plasticitymentioning

confidence: 58%

“…All the experiments were performed in accordance with the European Communities Council Directive (86/609/EEC) and with approval of the Institutional Animal Care and Use Committee of the University of Tor Vergata. Vibratome-cut coronal corticostriatal slices (200 -300 m) from the dorsal striatum were prepared for electrophysiological recordings as described previously (Centonze et al, 2004a) and then transferred to a recording chamber submerged in a continuously flowing artificial CSF (ACSF) (33°C, 2-3 ml/min) gassed with 95% O 2 -5% CO 2 . The composition of the control solution was (in mM) 126 NaCl, 2.5 KCl, 1.2 MgCl 2 , 1.2 NaH 2 PO 4 , 2.4 CaCl 2 , 11 glucose, and 25 NaHCO 3 .…”

Section: Electrophysiologymentioning

confidence: 99%

d-Aspartate Prevents Corticostriatal Long-Term Depression and Attenuates Schizophrenia-Like Symptoms Induced by Amphetamine and MK-801

et al. 2008

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IntroductionSchizophrenia (SCZ) is a severe mental disorder afflicting ϳ1% of the population worldwide. Despite decades of intensive research, the precise etiology of this devastating mental illness remains, so far, an unresolved puzzle (Sawa and Snyder, 2002). It has been proposed that dysfunction of dopaminergic neurotransmission occurs in SCZ patients (Snyder, 1976); however, a large body of evidence recently proposed that abnormal serotonergic and glutamatergic neurotransmission might also be implicated in the pathophysiological processes leading to the development of schizophrenia (González-Maeso et al., 2008). Compelling evidence from genetic, brain imaging, and clinical studies strongly suggests that psychotic symptoms might be associated with a persistent hypoglutamatergic transmission involving reduced NMDA receptor (NMDAR) activation (Tsai and Coyle, 2002). This hypothesis is mainly based on two fundamental observations: first, administration to healthy subjects of noncompetitive NMDAR antagonists, such as phencyclidine (PCP) or ketamine, results in severe mental symptoms resembling those of schizophrenic patients; second, administration of PCP to psychotic patients exacerbates positive and negative symptoms and worsens their cognitive functions (Javitt and Zukin, 1991;Olney and Farber, 1995). Together, these findings suggest that interventions able to enhance NMDAR transmission might be beneficial for the treatment of SCZ (Kristiansen et al., 2007). In particular, administration of D-serine to clozapine-treated patients ameliorates their positive, negative, and cognitive deficits (Tsai et al., 1999).D-Serine is a D-amino acid occurring in the mammalian forebrain throughout postnatal lifetime (Schell et al., 1995), which acts as an endogenous ligand at strychnine-insensitive glycinebinding site of NMDAR (Martineau et al., 2006). The striking discovery that D-serine could have therapeutic efficacy led to intensive investigations of the possible central functions of "unusual" free D-amino acids. Another D-amino acid, named D-aspartate, occurs in the mammalian brain. D-Aspartate levels are high in the embryonic phase and dramatically decrease during postnatal life, in concomitance with increased expression of D-aspartate oxidase (DDO), the enzyme responsible for its deg- radation (Schell et al., 1997;Errico et al., 2006;Huang et al., 2006). In contrast to D-serine, now well characterized for its implication in NMDAR-dependent functions, the role of D-aspartate in the CNS remains elusive.We have shown previously that D-aspartate enhances hippocampal NMDAR-dependent long-term potentiation (LTP) (Errico et al., 2008a). In the present work, we examined whether higher levels of this in-embryo-occurring molecule might increase glutamatergic transmission and exert antipsychotic effects in adult animals. Using genetic and pharmacological interventions able to enhance D-aspartate levels, we tested the ability of this D-amino acid to modulate cognition and gating abilities, which are thought, when altered, to be in...

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“…Furthermore, animal research indicates that an interaction of dopamine and NMDA receptor activation (Tseng and O'Donnell, 2004) might be affected by antipsychotic medication (Centonze et al, 2004). This could be an interesting target for future translational pharmacological research, which might help to identify specific factors underlying the variability of treatment responses.…”

Section: Discussionmentioning

confidence: 99%

Reduced Prefrontal-Parietal Effective Connectivity and Working Memory Deficits in Schizophrenia

et al. 2012

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The neural mechanisms behind cognitive deficits in schizophrenia still remain unclear. Functional neuroimaging studies on working memory (WM) yielded inconsistent results, suggesting task performance as a moderating variable of prefrontal activation. Beyond regional specific activation, disordered integration of brain regions was supposed as a critical pathophysiological mechanism of cognitive deficits in schizophrenia. Here, we first hypothesized that prefrontal activation implicated in WM depends primarily on task performance and therefore stratified participants into performance subgroups. Second, in line with the dysconnectivity hypothesis, we asked whether connectivity in the prefrontal-parietal network underlying WM is altered in all patients. We used functional magnetic resonance imaging in human subjects (41 schizophrenia patients, 42 healthy controls) and dynamic causal modeling to examine effective connectivity during a WM task. In line with our first hypothesis, we found that prefrontal activation was differentially modulated by task performance: there was a significant task by group by performance interaction revealing an increase of activation with performance in patients and a decrease with performance in controls. Beyond that, we show for the first time that WM-dependent effective connectivity from prefrontal to parietal cortex is reduced in all schizophrenia patients. This finding was independent of performance. In conclusion, our results are in line with the highly influential hypothesis that the relationship between WM performance and prefrontal activation follows an inverted U-shaped function. Moreover, this study in a large sample of patients reveals a mechanism underlying prefrontal inefficiency and cognitive deficits in schizophrenia, thereby providing direct experimental evidence for the dysconnectivity hypothesis.

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Chronic Haloperidol Promotes Corticostriatal Long-Term Potentiation by Targeting Dopamine D2L Receptors

Cited by 91 publications

References 75 publications

Genetic triple dissociation reveals multiple roles for dopamine in reinforcement learning

Genetic triple dissociation reveals multiple roles for dopamine in reinforcement learning

d-Aspartate Prevents Corticostriatal Long-Term Depression and Attenuates Schizophrenia-Like Symptoms Induced by Amphetamine and MK-801

Reduced Prefrontal-Parietal Effective Connectivity and Working Memory Deficits in Schizophrenia

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