Does the dopamine hypothesis explain schizophrenia?

Lau, Chi-Ieong; Wang, Han-Cheng; Hsu, Jung-Lung; Liu, Mu-En

doi:10.1515/revneuro-2013-0011

Cited by 77 publications

(53 citation statements)

References 39 publications

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“…In recent years, there has been growing interest in gaining better understanding of the neural correlates of risk/reward-based decision-making due to growing awareness that variability in decision-making is both a core feature and a potential risk factor for the development of a variety of psychiatric disorders (Christopher et al, 2013; Lau et al, 2013; Morales and Pickel 2012; Park and Kang 2013; Porcelli et al, 2011). Findings from recent preclinical and human neuroimaging studies suggest that dysregulation in brain DA neurotransmission may underlie some of these relationships (Griffiths, Morris, Balleine 2014; Sweitzer, Donny, Hariri 2012).…”

Section: 0 Discussionmentioning

confidence: 99%

“…Derangements in corticolimbic DA function seem to be an underlying feature of most neuropsychiatric disorders characterized by maladaptive decision making (Christopher et al, 2013; Lau et al, 2013; Morales and Pickel 2012; Park and Kang 2013; Porcelli et al, 2011). Nevertheless, there is still a paucity of research to delineate the precise role that regional brain DA function may play in decision-making in either clinical or non-clinical populations.…”

Section: 0 Introductionmentioning

confidence: 99%

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Risky decision-making and ventral striatal dopamine responses to amphetamine: A positron emission tomography [11C]raclopride study in healthy adults

et al. 2015

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Recent functional magnetic resonance imaging (fMRI) studies have provided compelling evidence that corticolimbic brain regions are integrally involved in human decision-making. Although much less is known about molecular mechanisms, there is growing evidence that the mesolimbic dopamine (DA) neurotransmitter system may be an important neural substrate. Thus far, direct examination of DA signaling in human risk-taking has centered onl gambling disorder. Findings from several positron emission tomography (PET) studies suggest that dysfunctions in mesolimbic DA circuits may play an important role in gambling behavior. Nevertheless, interpretation of these findings is currently hampered by a need for better understanding of how individual differences in regional DA function influence normative decision-making in humans. To further our understanding of these processes, we used [11C]raclopride PET to examine associations between ventral striatal (VS) DA responses to amphetamine (AMPH) and risky decision-making in a sample of healthy young adults with no history of psychiatric disorder, Forty-five male and female subjects, ages 18–29 years, completed a computerized version of the IOWA Gambling Task. Participants then underwent two 90-minute PET studies with high specific activity [11C]raclopride. The first scan was preceded by intravenous saline; the second, by intravenous AMPH (0.3 mg/kg). Findings of primary analyses showed that less advantageous decision-making was associated with greater right VS DA release; the relationship did not differ as a function of gender. No associations were observed between risk-taking and left VS DA release or baseline D2/D3 receptor availability in either hemisphere. Overall, the results support notions that variability in striatal DA function may mediate inter-individual differences in risky decision-making in healthy adults, further suggesting that hypersensitive DA circuits may represent a risk pathway in this population.

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Section: 0 Discussionmentioning

confidence: 99%

Section: 0 Introductionmentioning

confidence: 99%

Risky decision-making and ventral striatal dopamine responses to amphetamine: A positron emission tomography [11C]raclopride study in healthy adults

et al. 2015

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“…Degeneration of DA-expressing neurons underlies the deficits in movement initiation and posture experienced by Parkinson’s disease patients (Lang and Lozano, 1998a; b). Dysregulation of DA neurons underlies the positive symptoms of schizophrenia (Moore et al, 1999; Goto and Grace, 2007; Lau et al, 2013). In view of the broad spectrum of brain functions in which the DAergic (DA) ventral mesencephalic tegmentum has a role and its clinicopathologic significance, it is critically important to understand its interconnections, both intrinsic and with other parts of the brain.…”

Section: Introductionmentioning

confidence: 99%

An update on the connections of the ventral mesencephalic dopaminergic complex

et al. 2014

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This review covers the intrinsic organization and afferent and efferent connections of the midbrain dopaminergic complex, comprising the substantia nigra, ventral tegmental area and retrorubral field, which house, respectively, the A9, A10 and A8 groups of nigrostriatal, mesolimbic and mesocortical dopaminergic neurons. In addition, A10dc (dorsal, caudal) and A10rv (rostroventral) extensions into, respectively, the ventrolateral periaqueductal gray and supramammillary nucleus are discussed. Associated intrinsic and extrinsic connections of the midbrain dopaminergic complex that utilize gamma-aminobutyric acid (GABA), glutamate and neuropeptides and various co-expressed combinations of these compounds are considered in conjunction with the dopamine-containing systems. A framework is provided for understanding the organization of masssive afferent systems descending and ascending to the midbrain dopaminergic complex from the telencephalon and brainstem, respectively. Within the context of this framework, the basal ganglia direct and indirect output pathways are treated in some detail. Findings from rodent brain are briefly compared with those from primates, including human. Recent literature is emphasized, including traditional experimental neuroanatomical and modern gene transfer and optogenetic studies. An attempt was made to provide sufficient background and cite a representative sampling of earlier primary papers and reviews so that people new to the field may find this to be a relatively comprehensive treatment of the subject.

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“…While the dopamine and glutamate hypotheses of schizophrenia are often presented as two independent central dogmas to understanding schizophrenia (Abi-Dargham 2004;Angrist et al 1974;Brisch et al 2014;Carlsson 1988;Gilmour et al 2012;Krystal et al 2003;Lau et al 2013;Tamminga 1998), the reality is schizophrenia is a heterogeneous disorder and therefore, it is very likely that elements of both hypotheses are correct. Accordingly, the sensitivity of rPAL to glutamatergic and dopaminergic challenges may be useful in the search for novel pharmacological treatments for schizophrenia, especially if the profiles of these impairments differ as this may allow the modeling of different underlying pathologies and symptom clusters (positive versus cognitive), within the same testing environment.…”

Section: Introductionmentioning

confidence: 99%

MK-801 and amphetamine result in dissociable profiles of cognitive impairment in a rodent paired associates learning task with relevance for schizophrenia

et al. 2015

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Rationale Paired associates learning (PAL) has been suggested to be predictive of functional outcomes in first episode psychosis and of conversion from mild cognitive impairment to Alzheimer's disease. An automated touch screen-based rodent PAL (rPAL) task has been developed and is sensitive to manipulations of the dopaminergic and glutamatergic system. Accordingly, rPAL when used with pharmacological models of schizophrenia, like NMDA receptor blockade with MK-801 or dopaminergic stimulation with amphetamine, may have utility as a translational model of cognitive impairment in schizophrenia.Objective The purpose of this study was to determine if amphetamine-and MK-801-induced impairment represent distinct models of cognitive impairment by testing their sensitivity to common antipsychotics and determine the relative contributions of D1 versus D2 receptors on performance of PAL. Method Rats were trained in rPAL and were then treated with MK-801, amphetamine, risperidone, haloperidol, quinpirole, SK-82958, or SCH-23390 alone and in combination. Results While both amphetamine and MK-801 caused clear impairments in accuracy, MK-801 induced a profound Bperseverative^type behavior that was more pronounced when compared to amphetamine. Moreover, amphetamineinduced impairments, but not the effects of MK-801, could be reversed by antipsychotics as well as the D1 receptor antagonist SCH-23390, suggesting a role for both the D1 and D2 receptor in the amphetamine impairment model. Conclusions These data suggest that amphetamine and MK-801 represent dissociable models of impairment in PAL, dependent on different underlying neurobiology. The ability to distinguish dopaminergic versus glutamatergic effects on performance in rPAL makes it a unique and useful tool in the modeling of cognitive impairments in schizophrenia.

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Does the dopamine hypothesis explain schizophrenia?

Cited by 77 publications

References 39 publications

Risky decision-making and ventral striatal dopamine responses to amphetamine: A positron emission tomography [11C]raclopride study in healthy adults

Risky decision-making and ventral striatal dopamine responses to amphetamine: A positron emission tomography [11C]raclopride study in healthy adults

An update on the connections of the ventral mesencephalic dopaminergic complex

MK-801 and amphetamine result in dissociable profiles of cognitive impairment in a rodent paired associates learning task with relevance for schizophrenia

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