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Titolo:
Effects of ketamine, MK-801, and amphetamine on regional brain 2-deoxyglucose uptake in freely moving mice
Autore:
Miyamoto, S; Leipzig, JN; Lieberman, JA; Duncan, GE;
Indirizzi:
Univ N Carolina, Dept Psychiat, Pharmacol & UNC Mental Hlth, Sch Med, Chapel Hill, NC 27599 USA Univ N Carolina Chapel Hill NC USA 27599 h Med, Chapel Hill, NC 27599 USA Univ N Carolina, Neurosci Clin Res Ctr, Sch Med, Chapel Hill, NC 27599 USAUniv N Carolina Chapel Hill NC USA 27599 h Med, Chapel Hill, NC 27599 USA
Titolo Testata:
NEUROPSYCHOPHARMACOLOGY
fascicolo: 4, volume: 22, anno: 2000,
pagine: 400 - 412
SICI:
0893-133X(200004)22:4<400:EOKMAA>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
CEREBRAL GLUCOSE-UTILIZATION; NONCOMPETITIVE NMDA ANTAGONIST; EMISSION TOMOGRAPHY PET; RAT PREFRONTAL CORTEX; HEALTHY-VOLUNTEERS; NUCLEUS-ACCUMBENS; INDUCED HYPERLOCOMOTION; DOPAMINE RELEASE; LOCOMOTOR STIMULATION; RECEPTOR ANTAGONISTS;
Keywords:
ketamine; animal model; schizophrenia; NMDA antagonist; limbic cortex; mice;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
86
Recensione:
Indirizzi per estratti:
Indirizzo: Miyamoto, S Univ N Carolina, Dept Psychiat, Pharmacol & UNC Mental Hlth, Sch Med, CB 7160, Chapel Hill, NC 27599 USA Univ N Carolina CB 7160 Chapel Hill NC USA 27599 NC 27599 USA
Citazione:
S. Miyamoto et al., "Effects of ketamine, MK-801, and amphetamine on regional brain 2-deoxyglucose uptake in freely moving mice", NEUROPSYCH, 22(4), 2000, pp. 400-412

Abstract

Although the pathophysiology of schizophrenia remains unclear, behavioral effects in humans induced by N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, provide direction for formulating new pharmacologic models of the illness. The purpose of the present study was to clarify the roles of NMDA receptor antagonism, as well as dopamine-releasing properties of ketamine, in regional brain metabolic activity and behavioral responses in mice. The effects of acute administration of ketamine (30 mg/kg, i.p.) were compared with those of the more selective non-competitive NMDA antagonist MK-801(0.3 and 0.5 mg/kg, i.p.), and amphetamine (4mg/kg, i.p.) on regional brain [C-14]-2-deoxyglucose (2-DG) uptake, by using a high resolution autoradiographic technique in the freely moving mice. Both ketamine and MK-801 induced substantial and similar neuroanatomically selective alterations in regional 2-DG uptake. Remarkable increases in 2-DG uptake in response to the NMDA antagonists were seen in limbic cortical regions, hippocampal formation, nucleus accumbens, select thalamic nuclei, and basolateral amygdala. The behavior of mice given amphetamine was similar to that of mice given MK-801. However, the brain activity patterns induced by amphetamine were distinctlydifferent from those observed after ketamine and MK-801 treatment. These results suggest that generalized behavioral activation and increased dopamine release are insufficient to account for the ketamine-induced alterations in regional uptake are likely related to a reduction in NMDA receptor function. The data also suggest that ketamine-induced changes in 2-DG uptake mayprovide a useful paradigm for translational research to better understand the pathophysiology of schizophrenia. (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.

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Documento generato il 22/01/20 alle ore 13:02:46