Neuropeptides, Dopamine, and Schizophreniaa

Nemeroff, Charles B.; Bissette, Garth

doi:10.1111/j.1749-6632.1988.tb42113.x

Cited by 34 publications

(15 citation statements)

References 86 publications

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“…Behavioral, neurochemical, and electrophysiological studies, have demonstrated that CCK can modulate dopamine activity in the mesolimbic system where both known CCK receptor subtypes, CCK A and CCK B , have been identified (for review see Crawley 1991). This has led to speculation that CCK may play a role in the pathophysiology of schizophrenia (Nemeroff and Bissette 1992;Nair et al 1986). Support for this has come from studies showing significantly lower CCK levels in the cerebrospinal fluid (Beinfeld and Garver 1991;Verbanck et al 1984) and postmortem brains (Schalling et al 1990) of drugfree schizophrenia patients as compared to matched controls.…”

mentioning

confidence: 88%

Antipsychotic Potential of CCK-Based Treatments: An Assessment Using the Prepulse Inhibition Model of Psychosis

Feifel

Reza

Robeck

1999

Neuropsychopharmacology

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confidence: 88%

Antipsychotic Potential of CCK-Based Treatments: An Assessment Using the Prepulse Inhibition Model of Psychosis

Feifel

Reza

Robeck

1999

Neuropsychopharmacology

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“…Opiates levels tend to parallel the severity of psychosis (Terenius et al, 1976;Lindstrom et al, 1978;Rimon et al, 1980;Marchesi et al, 1995), suggesting involvement of this neurochemical effect in schizophrenia neuropathology (Volavka et al, 1979;Schmauss and Emrich, 1985;Nemeroff and Bissette, 1988).…”

Section: Abnormal Opioidergic Function May Impair Liking Processes Inmentioning

confidence: 99%

“…On the basis of the hypothesis that opioidergic mechanisms are involved in the pathophysiology and symptoms of schizophrenia (Volavka et al, 1979;Schmauss and Emrich, 1985;Nemeroff and Bissette, 1988), opioid antagonists were evaluated for potential antipsychotic efficacy in numerous clinical trials (McNicholas and Martin, 1984;Nemeroff and Bissette, 1988;Welch and Thompson, 1994). On the whole, they were safe and well tolerated and resulted in significant improvements of various aspects of schizophrenic symtomatology such as positive and deficit symptoms, polydipsia, alcoholism, and tardive dyskinesia in some (Watson et al, 1978;Lehmann et al, 1979;Berger et al, 1981;Nishikawa et al, 1994a, b;Marchesi et al, 1995;Petrakis et al, 2004;Wonodi et al, 2004), but not all (Volavka et al, 1977;Pickar et al, 1982) participants.…”

Section: Opioid Antagonists May Improve Hedonic Deficits In Patients mentioning

confidence: 99%

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

133

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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“…Subsequently, several other common psychomotor disorders, including schizophrenia and Tourette's syndrome, have been linked to alterations in neostriatal dopaminergic signaling (Nemeroff and Bissette, 1988;Erenberg, 1992). In recent years, significant progress has been made in characterizing the membrane receptors transducing the signals of dopamine in the neostriatum and the brain in general.…”

Section: Abstract: Medium Spiny Neurons; Single-cell Pcr; Voltage CLmentioning

confidence: 99%

“…Because of the strong correlation between peptide expression and projection site, medium spiny neurons were divided into three groups on the basis of expression of mRNA for enkephalin (ENK) and substance P (SP The signaling pathways activated by dopamine in the neostriatum have been the subject of intense study since it was discovered that the loss of dopamine leads to the psychomotor symptoms of Parkinson's disease (Hornykiewcz, 1973). Subsequently, several other common psychomotor disorders, including schizophrenia and Tourette's syndrome, have been linked to alterations in neostriatal dopaminergic signaling (Nemeroff and Bissette, 1988;Erenberg, 1992). In recent years, significant progress has been made in characterizing the membrane receptors transducing the signals of dopamine in the neostriatum and the brain in general.…”

mentioning

confidence: 99%

Coordinated Expression of Dopamine Receptors in Neostriatal Medium Spiny Neurons

Surmeíer

Yan

Song

1997

Advances in Pharmacology

164

196

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In recent years, the distribution of dopamine receptor subtypes among the principal neurons of the neostriatum has been the subject of debate. Conventional anatomical and physiological approaches have yielded starkly different estimates of the extent to which D 1 and D 2 class dopamine receptors are colocalized. One plausible explanation for the discrepancy is that some dopamine receptors are present in physiologically significant numbers, but the mRNA for these receptors is not detectable with conventional techniques. To test this hypothesis, we examined the expression of DA receptors in individual neostriatal neurons by patch-clamp and RT-PCR techniques. Because of the strong correlation between peptide expression and projection site, medium spiny neurons were divided into three groups on the basis of expression of mRNA for enkephalin (ENK) and substance P (SP The signaling pathways activated by dopamine in the neostriatum have been the subject of intense study since it was discovered that the loss of dopamine leads to the psychomotor symptoms of Parkinson's disease (Hornykiewcz, 1973). Subsequently, several other common psychomotor disorders, including schizophrenia and Tourette's syndrome, have been linked to alterations in neostriatal dopaminergic signaling (Nemeroff and Bissette, 1988;Erenberg, 1992). In recent years, significant progress has been made in characterizing the membrane receptors transducing the signals of dopamine in the neostriatum and the brain in general. How these receptors are distributed among the principal neuronal cell types in the neostriatum has been the subject of debate (Surmeier et al., 1993). This controversy stems primarily from discrepancies in the results obtained from functional studies on the one hand and anatomical studies on the other. The most compelling anatomical data are in situ hybridization studies suggesting that D 1a and D 2 mRNA are segregated primarily in the two major efferent neostriatal populations (Gerfen, 1992; LeMoine and Bloch, 1995). In particular, D 1a receptor mRNA is found in substance P-expressing (SP) neurons projecting to the substantia nigra, whereas D 2 receptor mRNA is found in enkephalin-expressing (ENK) neurons projecting exclusively to the globus pallidus. More recent immunocytochemical work supports this conclusion (Hersch et al., 1995), although others have reported significant degrees of receptor protein colocalization .Functional studies, on the other hand, repeatedly have observed responses to D 1 and D 2 class agonists that are difficult to explain if these receptor classes are not colocalized (Uchimura et al., 1986;Akaike et al., 1987;Cepeda et al., 1993; for review, see Surmeier et al., 1993). The most compelling evidence comes from patch-clamp studies of acutely isolated neostriatal neuronswhere synaptic interactions have been removed-showing neuromodulatory effects of both D 1 and D 2 class agonists in the same cell (Surmeier et al., 1992). In this study, it was also shown that neurons projecting axons to the substantia nigra coexp...

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Neuropeptides, Dopamine, and Schizophreniaa

Cited by 34 publications

References 86 publications

Antipsychotic Potential of CCK-Based Treatments: An Assessment Using the Prepulse Inhibition Model of Psychosis

Antipsychotic Potential of CCK-Based Treatments: An Assessment Using the Prepulse Inhibition Model of Psychosis

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

Coordinated Expression of Dopamine Receptors in Neostriatal Medium Spiny Neurons

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