ACP-103, a 5-HT2A/2C inverse agonist, potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and nucleus accumbens

Li, Zhu; Ichikawa, Junichiro; Huang, Mei; Prus, Adam J.; Dai, Jin; Meltzer, Herbert Y.

doi:10.1007/s00213-005-0170-9

Cited by 58 publications

(43 citation statements)

References 34 publications

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“…On the other hand, haloperidol increased DA levels in the frontal cortex of Nur77 +/+ mice as previously reported (Li et al 2005), but this effect is blunted in Nur77 −/− mice. Since COMT is mandatory for DA clearance in the frontal cortex (Bilder et al 2004), one might expect that reduced COMT levels would have instead exacerbated haloperidol effects on DA levels in Nur77 −/− mice.…”

Section: Discussionsupporting

confidence: 88%

Nur77 Gene Knockout Alters Dopamine Neuron Biochemical Activity and Dopamine Turnover

Gilbert

Morissette

St-Hilaire

et al. 2006

Biological Psychiatry

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Section: Discussionsupporting

confidence: 88%

Nur77 Gene Knockout Alters Dopamine Neuron Biochemical Activity and Dopamine Turnover

Gilbert

Morissette

St-Hilaire

et al. 2006

Biological Psychiatry

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“…Recent data suggests that atypical antipsychotic medications change lipid metabolism (Ferno et al, 2005), an effect that may also be related to the weight gain associated with many atypical antipsychotics (Bartzokis, 2002). Other mechanisms are consistent with neurochemicallybased models that suggest increased prefrontal cortex dopaminergic neurotransmission underlies some of the beneficial effects of atypical antipsychotics (Barch and Carter, 2005;Eltayb et al, 2005;Li et al, 2005). Consistent with the possibility that this effect could be mitigated by oligodendrocytes, in vitro models have suggested that dopamine stimulation may be protective of oligodendrocytes (Belachew et al, 1999;Rosin et al, 2005) and/or promote the genesis of new cells (Van Kampen et al, 2004).…”

Section: Discussionmentioning

confidence: 65%

Differential effects of typical and atypical antipsychotics on brain myelination in schizophrenia

Bartzokis

Nuechterlein

et al. 2007

Schizophrenia Research

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Context-Imaging and post-mortem studies provide converging evidence that patients with schizophrenia have a dysregulated developmental trajectory of frontal lobe myelination even in adulthood. Atypical antipsychotics have been shown to have a wide spectrum of efficacy across multiple psychiatric diseases and to be particularly efficacious in treatment resistant cases of disorders such as schizophrenia.Objective-To test the a priori hypothesis that antipsychotic medications may differentially impact frontal lobe myelination in patients with schizophrenia.Design, setting, and participants-Participants ranged in age from 18-35 years, were all male, and were recruited by a single group of investigators using the same criteria. Two cohorts of subjects with schizophrenia early in their disease who were treated either with oral risperidone (Ris) or fluphenazine decanoate (Fd) were imaged in conjunction with cohorts of healthy controls. Each cohort was imaged using a different MRI instrument using identical imaging sequences. Main outcome measure-MRI measures of frontal lobe white matter volume.Results-We estimated differences due to differences in the MRI instruments used in the two studies in the two healthy control groups matched to the patient samples, adjusting for age and other covariates. We then statistically removed those differences (which we assumed were instrument artifacts) from the data in the schizophrenia samples by subtraction. Relative to the differences seen in controls, the two groups of schizophrenic patients differed in their pattern of frontal lobe structure with the Ris-treated group having significantly larger white matter volume than the Fd group.

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“…Shilliam and Dawson (2005) demonstrated that this increase was confined to the shell of the NAc and did not occur in the NAc core. We have previously shown that 5-HT 2C -receptor antagonism, in combination with D 2 -receptor antagonism, may contribute to the ability of these agents to enhance DA release in the NAc (Bonaccorso et al, 2002;Li et al, 2005). The potent 5-HT 2C antagonist, SB242084, significantly potentiated low-dose haloperidolinduced increase in DA release in the NAc .…”

Section: Da Effluxmentioning

confidence: 95%

“…ASE, in this study, at doses less than 0.5 mg/kg, also showed preferential increase in cortical and HIP DA efflux compared with in the NAc. This action is due, in part, to blockade of 5-HT 2A receptors in the cerebral cortex and relatively weaker or negligible occupation of D 2 and D 1 receptors (Matsubara et al, 1993), since it can be mimicked by the combination of potent 5-HT 2A antagonism and weak blockade of D 2 receptors (Liegeois et al, 2002;Bonaccorso et al, 2002;Li et al, 2005). As reported by Schotte et al (1996), these agents, including clozapine, risperidone, 9-hydroxyrisperidone (paliperidone), olanzapine, pipamperone, quetiapine, sertindole, ziprasidone, and zotepine, also have higher occupancy in the rat cortex and striatum of 5-HT 2A than D 2 receptors, respectively, at all but the highest doses studied.…”

Section: Da Effluxmentioning

confidence: 99%

“…The relatively high occupancy of 5-HT 2A compared with the D 2 receptor may be critically important for some atypical antipsychotic drug actions, such as low EPS and efficacy in treatment-resistant schizophrenia (Meltzer et al, 1989(Meltzer et al, , 2003(Meltzer et al, , 2008. This profile has also been proposed as an important component of the preferential release of cortical DA by relatively specific ligands for these receptors, for example, M 100907, SR 43469B, or ACP-103, and haloperidol (Liegeois et al, 2002;Bonaccorso et al, 2002;Li et al, 2005), as well as clozapine, olanzapine, risperidone, and other atypical antipsychotic drugs, which are more potent 5-HT 2A than D 2 antagonists (Kuroki et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Asenapine Increases Dopamine, Norepinephrine, and Acetylcholine Efflux in the Rat Medial Prefrontal Cortex and Hippocampus

Huang

Dai

et al. 2008

Neuropsychopharmacol

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Atypical antipsychotic drugs, which are more potent direct acting antagonists of brain serotonin (5-HT) 2A than dopamine (DA) D 2 receptors, preferentially enhance DA and acetylcholine (ACh) efflux in the rat medial prefrontal cortex (mPFC) and hippocampus (HIP), compared with the nucleus accumbens (NAc). These effects may contribute to their ability, albeit limited, to improve cognitive function and negative symptoms in patients with schizophrenia. Asenapine (ASE), a new multireceptor antagonist currently in development for the treatment of schizophrenia and bipolar disorder, has complex serotonergic properties based upon relatively high affinity for multiple serotonin (5-HT) receptors, particularly 5-HT 2A and 5-HT 2C receptors. In the current study, the effects of ASE on DA, norepinephrine (NE), 5-HT, ACh, glutamate, and g-aminobutyric acid (GABA) efflux in rat mPFC, HIP, and NAc were investigated with microdialysis in awake, freely moving rats. ASE at 0.05, 0.1, and 0.5 mg/kg (s.c.), but not 0.01 mg/kg, significantly increased DA efflux in the mPFC and HIP. Only the 0.5 mg/kg dose enhanced DA efflux in the NAc. ASE, at 0.1 and 0.5 mg/kg, significantly increased ACh efflux in the mPFC, but only the 0.5 mg/kg dose of ASE increased HIP ACh efflux. ASE did not increase ACh efflux in the NAc at any of the doses tested. The effect of ASE (0.1 mg/kg) on DA and ACh efflux was blocked by pretreatment with WAY100635, a 5-HT 1A antagonist/D 4 agonist, suggesting involvement of indirect 5-HT 1A agonism in both the actions. ASE, at 0.1 mg/kg, increased NE, but not 5-HT, efflux in the mPFC and HIP. ASE, at 0.1 mg/kg (s.c.), had no effect on glutamate and GABA efflux in either the mPFC or NAc. These findings indicate that ASE is similar to clozapine and other atypical antipsychotic drugs in preferentially increasing the efflux of DA, NE, and ACh in the mPFC and HIP compared with the NAC, and suggests that, like these agents, it may also improve cognitive function and negative symptoms in patients with schizophrenia.

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ACP-103, a 5-HT2A/2C inverse agonist, potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and nucleus accumbens

Cited by 58 publications

References 34 publications

Nur77 Gene Knockout Alters Dopamine Neuron Biochemical Activity and Dopamine Turnover

Nur77 Gene Knockout Alters Dopamine Neuron Biochemical Activity and Dopamine Turnover

Differential effects of typical and atypical antipsychotics on brain myelination in schizophrenia

Asenapine Increases Dopamine, Norepinephrine, and Acetylcholine Efflux in the Rat Medial Prefrontal Cortex and Hippocampus

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