Comparative analysis of acute and chronic administration of haloperidol and clozapine using [3H] 2-deoxyglucose metabolic mapping

Wotanis, Jill; Hanák, S; Wettstein, Joseph G.; Black, Mark D.

doi:10.1016/s0920-9964(02)00230-x

Cited by 11 publications

(10 citation statements)

References 44 publications

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“…The effects of administration of clozapine and haloperidol were relatively small in contrast to the other findings reported here, remaining broadly in line with previous studies (Duncan et al, 1998a, Cochran et al, 2002, Wotanis et al, 2003. Clozapine and haloperidol also had minimal effect on mPFC-mVS coherence when administered alone.…”

Section: Discussionsupporting

confidence: 91%

Dissociable Effects of Antipsychotics on Ketamine-Induced Changes in Regional Oxygenation and Inter-Regional Coherence of Low Frequency Oxygen Fluctuations in the Rat

Ishiwari

Conway

et al. 2014

Neuropsychopharmacol

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Typical and atypical antipsychotics have been shown to alleviate N-methyl-D-aspartate (NMDA) receptor antagonist-induced BOLD signals in healthy humans and animals to differing degrees; factors that might relate to their different molecular mechanisms and clinical profiles. Recent studies have also extended these investigations to the analysis of resting state functional connectivity measures of BOLD signals in different brain regions. Using constant potential amperometry, we examined the effects of the NMDA receptor antagonist S-(+)-ketamine on tissue oxygen levels in medial prefrontal cortex (mPFC) and medial ventral striatum (mVS), and temporal coherence of low-frequency oxygen fluctuations between these regions in freely moving rats. Furthermore, we assessed the extent to which the atypical antipsychotic clozapine and the typical antipsychotic haloperidol could modulate the effects of S-(+)-ketamine on these measures. Acute S-(+)-ketamine (5-25 mg/kg) produced dose-dependent increases in both tissue O2 levels and coherence. Although effects of clozapine and haloperidol alone were relatively minor, their effects on ketamine-induced signals were markedly more distinct. Clozapine dose-dependently attenuated the absolute S-(+)-ketamine (25 mg/kg) O2 signal in both regions, and also attenuated ketamine-induced increases in regional coherence. Haloperidol had no effect on the absolute ketamine O2 signal yet potentiated increases in regional coherence. The dissociable effects of haloperidol and clozapine on ketamine-induced hyperoxygenation and mPFC-mVS coherence elucidate potentially important mechanistic differences between these classes of pharmacology. This study demonstrates for the first time that in vivo amperometry can measure both regional brain tissue O2 levels and inter-regional coherence, advancing BOLD-like measurements of functional connectivity into awake, unconstrained animals.

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Section: Discussionsupporting

confidence: 91%

Dissociable Effects of Antipsychotics on Ketamine-Induced Changes in Regional Oxygenation and Inter-Regional Coherence of Low Frequency Oxygen Fluctuations in the Rat

Ishiwari

Conway

et al. 2014

Neuropsychopharmacol

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“…This has also been reported after acute administration of D2 but not D1 DA receptor antagonists [89], and after lesions of the nigrostriatal system [90] [91]. HAL also reportedly decreases 2-DG uptake in the raphe [92] [85] , and while this area does not express D2 receptors, it does receive more extensive glutamatergic innervation from the STN than previously thought [93]. HAL also reportedly decreases 2-DG uptake in the raphe [92] [85] , and while this area does not express D2 receptors, it does receive more extensive glutamatergic innervation from the STN than previously thought [93].…”

Section: -Deoxyglucose (2-dg) Uptakesupporting

confidence: 64%

“…Second, treatment with clozapine (which is not associated with acute EPS or chronic orofacial dyskinesias in animal models) was found to have a similar profile of 2-DG uptake in the GP and SN [84], M1 and GP [75] [85]. Second, treatment with clozapine (which is not associated with acute EPS or chronic orofacial dyskinesias in animal models) was found to have a similar profile of 2-DG uptake in the GP and SN [84], M1 and GP [75] [85].…”

Section: -Deoxyglucose (2-dg) Uptakementioning

confidence: 97%

“…The effects of acute HAL treatment on 2-DG uptake were found to be age-dependent in the rat, with HAL-induced decreases in LCGU being most pronounced in 33 month old rats [83]. In two studies directly comparing acute (1mg/kg), and chronic (0.5 or 1.0 mg/kg/day, for 21 days) HAL treatment on 2-DG uptake, an adaptation to HAL has been reported, with fewer regions being effected and the magnitude of decreased 2-DG uptake being reduced after 21 days of HAL treatment [92] [85]. Fig.…”

Section: -Deoxyglucose (2-dg) Uptakementioning

confidence: 99%

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Neurobiological Basis of Dyskinetic Effects Induced by Antipsychotics: the Contribution of Animal Models

Creed¹,

Nóbrega²

2013

Current Medicinal Chemistry

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Tardive dyskinesia (TD) is a movement disorder characterized by abnormal involuntary facial movements induced by chronic therapy with classical antipsychotic medications. Currently, there is no satisfactory pharmacotherapy for TD, which represents a major limitation to therapy with classical antipsychotics. In order to develop or optimize therapies for TD, and to develop new APDs with lower indices of motor side effects, the pathology underlying TD must first be understood. The use of animal models has been used to further this objective. Here, we review different preparations that have been used to model TD and discuss the contribution of neuroimaging studies conducted in these models. Studies in animal models have lead to several hypotheses of TD pathology, although none has yet emerged as the ultimate underlying cause of this syndrome. We discuss alterations in functional indices, neuron and synapse morphology and changes in specific neurotransmitter systems that have been described in animal models of TD, and outline how these findings have contributed to our understanding of antipsychotic-induced dyskinesias. We conclude that several non-mutually exclusive theories of TD are supported by animal studies, including increases in oxidative stress leading to structural and functional changes in specific neurotransmitter systems. Elucidating the mechanisms underlying TD neuropathology partly through the use of animal models will lead to the development of APDs with superior side effect profiles or more effective therapies for TD.

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“…Therefore, the allocation of subjects to each of these three groups was nonrandomized, but based on the medication prescribed by the in-charge clinician at the time of MRI scan. According to the existing literature on brain changes following administration of antipsychotics (Chakos et al, 1994;Cohen et al, 2003;Christensen et al, 2004;Grunder et al, 2003;Honey et al, 1999;Huang et al, 1999;Miller et al, 1997aMiller et al, , b, 2001Wotanis et al, 2003), the mean length of treatment of 8 weeks of our sample would be sufficient to observe brain changes in association with antipsychotic use.…”

Section: Pharmacological Treatmentmentioning

confidence: 97%

Different Effects of Typical and Atypical Antipsychotics on Grey Matter in First Episode Psychosis: the ÆSOP Study

Dazzan

Morgan

Orr

et al. 2005

Neuropsychopharmacol

248

160

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Typical antipsychotic drugs act on the dopaminergic system, blocking the dopamine type 2 (D2) receptors. Atypical antipsychotics have lower affinity and occupancy for the dopaminergic receptors, and a high degree of occupancy of the serotoninergic receptors 5-HT2A. Whether these different pharmacological actions produce different effects on brain structure remains unclear. We explored the effects of different types of antipsychotic treatment on brain structure in an epidemiologically based, nonrandomized sample of patients at the first psychotic episode. Subjects were recruited as part of a large epidemiological study (AESOP: aetiology and ethnicity in schizophrenia and other psychoses). We evaluated 22 drug-free patients, 32 on treatment with typical antipsychotics and 30 with atypical antipsychotics. We used high-resolution MRI and voxel-based methods of image analysis. The MRI analysis suggested that both typical and atypical antipsychotics are associated with brain changes. However, typicals seem to affect more extensively the basal ganglia (enlargement of the putamen) and cortical areas (reductions of lobulus paracentralis, anterior cingulate gyrus, superior and medial frontal gyri, superior and middle temporal gyri, insula, and precuneus), while atypical antipsychotics seem particularly associated with enlargement of the thalami. These changes are likely to reflect the effect of antipsychotics on the brain, as there were no differences in duration of illness, total symptoms scores, and length of treatment among the groups. In conclusion, we would like to suggest that even after short-term treatment, typical and atypical antipsychotics may affect brain structure differently.

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Comparative analysis of acute and chronic administration of haloperidol and clozapine using [3H] 2-deoxyglucose metabolic mapping

Cited by 11 publications

References 44 publications

Dissociable Effects of Antipsychotics on Ketamine-Induced Changes in Regional Oxygenation and Inter-Regional Coherence of Low Frequency Oxygen Fluctuations in the Rat

Dissociable Effects of Antipsychotics on Ketamine-Induced Changes in Regional Oxygenation and Inter-Regional Coherence of Low Frequency Oxygen Fluctuations in the Rat

Neurobiological Basis of Dyskinetic Effects Induced by Antipsychotics: the Contribution of Animal Models

Different Effects of Typical and Atypical Antipsychotics on Grey Matter in First Episode Psychosis: the ÆSOP Study

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