Electrophysiological Interactions between Striatal Glutamatergic and Dopaminergic Systems

West, Anthony R.; Floresco, Stan; Charara, Ali; Rosenkranz, J. Amiel; Grace, Anthony A.

doi:10.1196/annals.1300.004

Cited by 100 publications

(89 citation statements)

References 124 publications

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“…The hypofrontality phenomenon has been potentially related to the disease process- (Lieberman et al, 1997;West et al, 2003;Laruelle, 2000) or drug-(Kalivas and Volkow, 2005) related diminished dopaminergic tone with corresponding decrease in the tonic glutamatergic activity.…”

Section: Neural and Motivational Changes In Schizophrenia And In Sudsmentioning

confidence: 99%

“…The limbic hyperdopaminergic state is further amplified through the long-term plasticity (Pierce and Kalivas, 1997) process of endogenous sensitization (Lieberman et al, 1997;Laruelle, 2000;Chambers et al, 2001;West et al, 2003). This is an autonomous, selfsustaining feedforward loop whereby a trivial event (eg, psychosocial stress) can mount escalating dopamine releases in the striatum, further worsening symptoms of psychosis (Laruelle, 2000).…”

Section: Neural and Motivational Changes In Schizophrenia And In Sudsmentioning

confidence: 99%

Section: Neurobiology Of Systems Mediating Food Rewardmentioning

confidence: 99%

“…Neuroimaging findings k Responsivity to natural rewards (summarized in Table 2) k In basal activity and in responsivity to drugs and natural rewards Little et al, 1999;Martin-Soelch et al, 2001a;Martin-Soelch et al, 2001b;Martin-Solch et al, 2001;Volkow et al, 2002a) Putative mechanisms k In tonic dopamine (Moore et al, 1999) owing to k in basal cortical dopaminergic and glutamatergic output (Lieberman et al, 1997;Laruelle, 2000;West et al, 2003) Altered tonic/phasic dopamine interaction caused by repeated drug administration (Grace, 2000;Goto and Grace, 2005) Motivational correlates k Sensitivity and responsivity to natural rewards and reinforcers (Table 2), that is, 'reward deficiency' (Comings and Blum, 2000) k Sensitivity and responsivity to natural rewards and reinforcers (Volkow et al, 2004a, b), that is, 'reward deficiency' (Comings and Blum, 2000) mActivity…”

Section: Neuroimaging Findingsmentioning

confidence: 99%

“…A closely related concept, derived from primate work, is the aberrant learning theory suggesting that learning of new rewards is encoded via interactions between tonic (baseline) and phasic spikes in dopaminegic neurons; phasic firing predicts new rewards (Schultz, 2001). Hence, neural adaptations to excessive dopaminergic trafficking in response to drugs (Breiter et al, 1997) or during psychotic episodes (Grace, 1991;Lieberman et al, 1997;Laruelle, 2000;West et al, 2003) may lead to low signal-to-noise detection capability for natural rewards along with 'profound overlearning of the motivational significance of cues that [either] predict delivery of drugs ' (Hyman, 2005) or are associated with psychotic contents resulting in 'aberrant salience ' (Kapur, 2003) for drug-or psychosis-related stimuli (detailed in the following sections).Mesolimbic dopaminergic pathways projecting from the vental tegmental area (VTA) to the nucleus accumbens (NAc), along with the LH, amygdala, and prefrontal cortex (PFC; Goldstein and Volkow, 2002;Volkow et al, 2004a), are responsible for the incentive motivational aspects of reward function. These are collectively termed 'wanting' processes (Kelley and Berridge, 2002;Pecina et al, 2003;Kelley, 2004b) and include conditioned learning of stimulus-reward association (McClure et al, 2003;Tobler et al, 2003;Berridge, 2004;Wise, 2004), reward prediction, and attribution of incentive salience to rewarding stimuli .…”

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confidence: 99%

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Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Elman

Borsook

Lukas

2006

Neuropsychopharmacol

138

142

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Obesity is highly prevalent among patients with schizophrenia and is associated with detrimental health consequences. Although excessive consumption of fast food and pharmacotherapy with such second-generation antipsychotic agents (SGAs) as clozapine and olanzapine has been implicated in the schizophrenia/obesity comorbidity, the pathophysiology of this link remains unclear. Here, we propose a mechanism based on brain reward function, a relevant etiologic factor in both schizophrenia and overeating. A comprehensive literature search on neurobiology of schizophrenia and of eating behavior was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) energy homeostasis, (2) food reward and hedonics, (3) reward function in schizophrenia, and (4) metabolic effects of the SGAs. A mesolimbic hyperdopaminergic state may render motivational/incentive reward system insensitive to low salience/palatability food. This, together with poor cognitive control from hypofunctional prefrontal cortex and enhanced hedonic impact of food, owing to exaggerated opioidergic drive (clinically manifested as pain insensitivity), may underlie unhealthy eating habits in patients with schizophrenia. Treatment with SGAs purportedly improves dopamine-mediated reward aspects, but at the cost of increased appetite and worsened or at least not improved opiodergic capacity. These effects can further deteriorate eating patterns. Pathophysiological and therapeutic implications of these insights need further validation via prospective clinical trials and neuroimaging studies. INTRODUCTIONObesity has reached pandemic proportions and it is rapidly surpassing smoking as a number one killer in the industrialized world (Sturm, 2002;Skidmore and Yarnell, 2004). Its annual cost to the American society is staggering, and is estimated to be around $117 billion owing to related illnesses and loss of productivity (National Institute of Diabetes and Digestive and Kidney Diseases, 2005).In schizophrenia, obesity is twice as prevalent as in the general public, afflicting over half this patient population (Allison et al, 1999a;Dixon et al, 2000; American Diabetes Association, 2004;Marder et al, 2004;Wirshing, 2004). Besides negative psychosocial impacts (distorted selfesteem and societal stigmatization) and medications noncompliance, schizophrenics appear to be particularly susceptible to the detrimental medical sequelae of obesity such as the 'Metabolic Syndrome', which is a cluster of cardiovascular risk factors, including abdominal adiposity, insulin resistance, impaired, glucose tolerance, dyslipidemia, and hypertension (McKee et al, 1986;Mukherjee et al, 1996;Brown et al, 2000;Haupt and Newcomer, 2002;Ryan and Thakore, 2002;Ryan et al, 2003;Holt et al, 2004;Kohen, 2004;Marder et al, 2004;Lieberman et al, 2005).Excessive body weight gain (BWG) could be attributed to a constellation of endocrine, molecular, genetic, demographic, and lifestyle-related factors. Provided that a common tra...

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Section: Neural and Motivational Changes In Schizophrenia And In Sudsmentioning

confidence: 99%