Acute d-amphetamine challenge in schizophrenia: Effects on cerebral glucose utilization and clinical symptomatology

Wolkin, Adam; Sanfilipo, Michael; Angrist, Burton; Duncan, Erica; Wieland, Susan; Wolf, Alfred P.; Brodie, Jonathan D.; Cooper, Thomas B.; Laska, Eugene; Rotrosen, John

doi:10.1016/0006-3223(94)90629-7

Cited by 32 publications

(15 citation statements)

References 40 publications

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“…At a low dose of 0.5 mg/kg i.p. D-amphetamine, comparable to what has been used in human studies when measuring rCBF or rCMR glc with PET (Devous et al, 2001;Wolkin et al, 1994), k* was increased in the nucleus accumbens and some layer IV of neocortical regions. This effect is consistent with a high D 2 -like receptor density in the nucleus accumbens, and with the reported lowdose activation of rCMR glc in this region.…”

Section: Discussionmentioning

confidence: 90%

“…Thus, one might image D 2 -like receptor-mediated activation of AA metabolism in human brain diseases thought to have disturbed DA neurotransmission, such as Parkinson disease (Chalon et al, 1999;Hayakawa et al, 1998Hayakawa et al, , 2001Ross et al, 2001), cocaine abuse (Ross et al, 1996), attention deficit hyperactivity disorder and schizophrenia (Matochik et al, 1993;Wolkin et al, 1994). Not only might amphetamine be used in this regard, but so might apomorphine, a D 1 /D 2 -like agonist, considering prior imaging of rCMR glc or rCBF in animals and humans given one or the other drug (Cleghorn et al, 1991;Devous et al, 2001;Ernst et al, 1997;McCulloch and Harper, 1977a;McCulloch et al, 1982;Wolkin et al, 1994). In Parkinson disease, for example, based on behavioral and fatty acid animal studies, we would predict increased k* responses to apomorphine because of increased expression of D 2 -like receptors in the basal ganglia, but reduced responses to amphetamine, because of reduced pre-synaptic dopaminergic elements (Chalon et al, 1999;Guttman, 1992;Hayakawa et al, 2001;Metz and Whishaw, 2002).…”

Section: Discussionmentioning

confidence: 99%

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D-Amphetamine Stimulates D₂Dopamine Receptor-Mediated Brain Signaling Involving Arachidonic Acid in Unanesthetized Rats

Bhattacharjee

Chang

White

et al. 2006

J Cereb Blood Flow Metab

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In rat brain, dopaminergic D 2 -like but not D 1 -like receptors can be coupled to phospholipase A 2 (PLA 2 ) activation, to release the second messenger, arachidonic acid (AA, 20:4n-6), from membrane phospholipids. In this study, we hypothesized that D-amphetamine, a dopamine-releasing agent, could initiate such AA signaling. The incorporation coefficient, k* (brain radioactivity/integrated plasma radioactivity) for AA, a marker of the signal, was determined in 62 brain regions of unanesthetized rats that were administered i.p. saline, D-amphetamine (2.5 or 0.5 mg/kg i.p.), or the D 2 -like receptor antagonist raclopride (6 mg/kg, i.v.) before saline or 2.5 mg/kg D-amphetamine. After injecting [1-14 C]AA intravenously, k* was measured by quantitative autoradiography. Compared to saline-treated controls, D-amphetamine 2.5 mg/kg i.p. increased k* significantly in 27 brain areas rich in D 2 -like receptors. Significant increases were evident in neocortical, extrapyramidal, and limbic regions. Pretreatment with raclopride blocked the increments, but raclopride alone did not alter baseline values of k*. In independent experiments, D-amphetamine 0.5 mg/kg i.p. increased k* significantly in only seven regions, including the nucleus accumbens and layer IV neocortical regions. These results indicate that D-amphetamine can indirectly activate brain PLA 2 in the unanesthetized rat, and that activation is initiated entirely at D 2 -like receptors. D-Amphetamine's lowdose effects are consistent with other evidence that the nucleus accumbens, considered a reward center, is particularly sensitive to the drug.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

D-Amphetamine Stimulates D₂Dopamine Receptor-Mediated Brain Signaling Involving Arachidonic Acid in Unanesthetized Rats

Bhattacharjee

Chang

White

et al. 2006

J Cereb Blood Flow Metab

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“…In the past, conventional experimental models of schizophrenia focused on the effects of d-amphetamine, primarily because these and other psychostimulants directly increased dopamine (DA) release and induced a paranoid psychotic state in healthy controls similar to schizophrenia (Angrist and Gershon 1970;Wolkin et al 1994). However, more recent models of schizophrenia focus on the effects of PCP and other NMDA antagonists, which produce psychoses that also incorporate the negative symptoms associated with schizophrenic illness (Javitt and Zukin 1991;Krystal et al 1994).…”

Section: To Explore the Role Of Endogenous Gaba In Nmda Antagonist Inmentioning

confidence: 99%

Gamma Vinyl-GABA Differentially Modulates NMDA Antagonist-Induced Increases in Mesocortical Versus Mesolimbic DA Transmission

Schiffer

Gerasimov

Hofmann

et al. 2001

Neuropsychopharmacology

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To explore the role of endogenous GABA in NMDA antagonist induced dopamine (DA) release, we used in vivo microdialysis to study the effects of pretreatment with ␥ -vinyl GABA (GVG) on phencyclidine (PCP)-inducedN-methyl-D-aspartate (NMDA) glutamate-receptor antagonists like phencyclidine (PCP) and ketamine, traditionally considered substances of abuse, have more recently assumed a compelling role in exploratory paradigms of schizophrenic psychoses (Javitt and Zukin 1991). In the past, conventional experimental models of schizophrenia focused on the effects of d-amphetamine, primarily because these and other psychostimulants directly increased dopamine (DA) release and induced a paranoid psychotic state in healthy controls similar to schizophrenia (Angrist and Gershon 1970;Wolkin et al. 1994). However, more recent models of schizophrenia focus on the effects of PCP and other NMDA antagonists, which produce psychoses that also incorporate the negative symptoms associated with schizophrenic illness (Javitt and Zukin 1991;Krystal et al. 1994). The psychotomimetic properties of NMDA antagonists provide a clinical foundation from which we can design novel treatment strategies targeted at diminishing aberrant neurochemical behavior. Investigations of the neurochemical interactions associated with NMDA antagonist-induced pathologies share the common denominator of increased subcortical DA concentrations and from this, many investigations have attempted to elucidate the events that produce abnormal DA activity. NMDA antagonists block excitatory amino acid (EAA) transmission at the NMDA receptor complex (Yamamoto et al. 1999). From this, many explanations suggest a hypo-glutamatergic state where diminished glutamatergic activity fails to activate the large number of inhibitory gamma aminobutyric acid (GABA) interneurons in the prefrontal cortex (PFC) (Yonezawa et al. 1998) or ventral tegmental area (VTA) (Bonci and Malenka 1999). This may produce dysfunctional cortical regulation of subcortical DA systems (Farber et al. 1998;Grace 1991). Indeed, local application of GABA receptor agonists dramatically reduces PCP-induced increases in PFC Yonezawa et al. 1998) and NAcc DA Wu et al. 1999).On the other hand, a solid body of evidence indicates that a hyperactive glutamatergic state mediates increases in DA activity secondary to NMDA antagonist administration. Microdialysis studies have demonstrated concurrent increases in glutamatergic and dopaminergic activity in the PFC, Nacc, and VTA in response to an NMDA antagonist challenge (Moghaddam et al. 1997;Karreman et al. 1996;Svensson et al. 1997;Takahata and Moghaddam 1998). Unanticipated increases in glutamatergic activity in response to NMDA antagonism were attributed to increased synaptic availability of glutamate at non-NMDA alpha-amino-3-hydroxy-5-metyloisoxazolo-4-propionate (AMPA)/kainate glutamate receptors.Consistent with this hypothesis, systemic and local pretreatment with AMPA/kainate glutamate receptor antagonists reduced or completely blocked dopaminergic responsi...

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“…Positive symptoms induced by amphetamines and cocaine include auditory hallucinations, thought disorder and grandiose delusions, and chronic amphetamine users have been found to score highly on the Positive and Negative Syndrome Scale (PANSS) [Angrist and Gershon, 1970;Harris and Batki, 2000;Wolkin et al 1994;Angrist et al 1974]. However, in a recent survey of effects associated with amphetamine use, we found that schizophrenia-like effects were relatively rare in regular users, and that experienced users ranked amphetamine behind ketamine and alcohol in terms of its propensity to cause thought disorder, and behind cannabis, psilocybin and ketamine in terms of likelihood of inducing hallucinations and delusions [Carhart-Harris et al 2013a].…”

Section: Dopaminergicmentioning

confidence: 99%

Drug models of schizophrenia

Steeds

Carhart‐Harris

Stone

2014

Therapeutic Advances in Psychopharmacology

113

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Schizophrenia is a complex mental health disorder with positive, negative and cognitive symptom domains. Approximately one third of patients are resistant to currently available medication. New therapeutic targets and a better understanding of the basic biological processes that drive pathogenesis are needed in order to develop therapies that will improve quality of life for these patients. Several drugs that act on neurotransmitter systems in the brain have been suggested to model aspects of schizophrenia in animals and in man. In this paper, we selectively review findings from dopaminergic, glutamatergic, serotonergic, cannabinoid, GABA, cholinergic and kappa opioid pharmacological drug models to evaluate their similarity to schizophrenia. Understanding the interactions between these different neurotransmitter systems and their relationship with symptoms will be an important step towards building a coherent hypothesis for the pathogenesis of schizophrenia.

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Acute d-amphetamine challenge in schizophrenia: Effects on cerebral glucose utilization and clinical symptomatology

Cited by 32 publications

References 40 publications

D-Amphetamine Stimulates D₂Dopamine Receptor-Mediated Brain Signaling Involving Arachidonic Acid in Unanesthetized Rats

D-Amphetamine Stimulates D₂Dopamine Receptor-Mediated Brain Signaling Involving Arachidonic Acid in Unanesthetized Rats

Gamma Vinyl-GABA Differentially Modulates NMDA Antagonist-Induced Increases in Mesocortical Versus Mesolimbic DA Transmission

Drug models of schizophrenia

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Acute d-amphetamine challenge in schizophrenia: Effects on cerebral glucose utilization and clinical symptomatology

Cited by 32 publications

References 40 publications

D-Amphetamine Stimulates D2Dopamine Receptor-Mediated Brain Signaling Involving Arachidonic Acid in Unanesthetized Rats

D-Amphetamine Stimulates D2Dopamine Receptor-Mediated Brain Signaling Involving Arachidonic Acid in Unanesthetized Rats

Gamma Vinyl-GABA Differentially Modulates NMDA Antagonist-Induced Increases in Mesocortical Versus Mesolimbic DA Transmission

Drug models of schizophrenia

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Product

Resources

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D-Amphetamine Stimulates D₂Dopamine Receptor-Mediated Brain Signaling Involving Arachidonic Acid in Unanesthetized Rats

D-Amphetamine Stimulates D₂Dopamine Receptor-Mediated Brain Signaling Involving Arachidonic Acid in Unanesthetized Rats