Comparison of brain metabolic activity patterns induced by ketamine, MK-801 and amphetamine in rats: support for NMDA receptor involvement in responses to subanesthetic dose of ketamine - PubMed (original) (raw)
Comparison of brain metabolic activity patterns induced by ketamine, MK-801 and amphetamine in rats: support for NMDA receptor involvement in responses to subanesthetic dose of ketamine
G E Duncan et al. Brain Res. 1999.
Abstract
Subanesthetic doses of NMDA receptor antagonists induce positive, negative and cognitive schizophrenia-like symptoms in healthy humans and precipitate psychotic reactions in stabilized schizophrenic patients. These findings suggest that defining neurobiologic effects induced by NMDA antagonists could guide the formulation of experimental models relevant to the pathophysiology of schizophrenia and antipsychotic drug action. Accordingly, the effects of subanesthetic doses of the non-competitive NMDA antagonists ketamine and MK-801 were examined on regional brain [14C]-2-deoxyglucose (2-DG) uptake in rats. The effects of these drugs were compared to those of amphetamine, in order to assess the potential role of generalized behavioral arousal, motor activity and dopamine release in brain metabolic responses to the NMDA antagonists. Subanesthetic doses of MK-801 and ketamine induced identical alterations in patterns of 2-DG uptake. The most pronounced increases in 2-DG for both NMDA antagonists were in the hippocampal formation and limbic cortical regions. By contrast, amphetamine treatment did not increase 2-DG uptake in these regions. In isocortical regions, ketamine and MK-801 reduced uptake in layers 3 and 4, creating a striking shift in the laminar pattern of 2-DG uptake in comparison to control conditions. After amphetamine, the fundamental laminar pattern of isocortical labeling was similar to saline-treated rats. Administration of ketamine and MK-801 decreased 2-DG uptake in the medial geniculate and inferior colliculus, whereas amphetamine tended to increase uptake in these regions. Since ketamine induced similar effects on regional 2-DG uptake as observed for the selective antagonists MK-801, the effects of ketamine are likely related to NMDA antagonistic properties of the drug. The distinct differences in brain 2-DG uptake induced by amphetamine and NMDA antagonists indicate that generalized behavioral arousal, and increased locomotor activity mediated by dopamine release, are not sufficient to account for the alterations in brain metabolic patterns induced by ketamine and MK-801. Thus, the dramatic alteration in regional 2-DG uptake induced by ketamine and MK-801 reflects a state selectively induced by reduced NMDA receptor function.
Similar articles
- Effects of ketamine, MK-801, and amphetamine on regional brain 2-deoxyglucose uptake in freely moving mice.
Miyamoto S, Leipzig JN, Lieberman JA, Duncan GE. Miyamoto S, et al. Neuropsychopharmacology. 2000 Apr;22(4):400-12. doi: 10.1016/S0893-133X(99)00127-X. Neuropsychopharmacology. 2000. PMID: 10700659 - Metabolic mapping of the rat brain after subanesthetic doses of ketamine: potential relevance to schizophrenia.
Duncan GE, Moy SS, Knapp DJ, Mueller RA, Breese GR. Duncan GE, et al. Brain Res. 1998 Mar 23;787(2):181-90. doi: 10.1016/s0006-8993(97)01390-5. Brain Res. 1998. PMID: 9518601 - Differential effects of clozapine and haloperidol on ketamine-induced brain metabolic activation.
Duncan GE, Leipzig JN, Mailman RB, Lieberman JA. Duncan GE, et al. Brain Res. 1998 Nov 23;812(1-2):65-75. doi: 10.1016/s0006-8993(98)00926-3. Brain Res. 1998. PMID: 9813244 - [Glutaminergic hypothesis of schizophrenia: clinical research studies with ketamine].
Mechri A, Saoud M, Khiari G, d'Amato T, Dalery J, Gaha L. Mechri A, et al. Encephale. 2001 Jan-Feb;27(1):53-9. Encephale. 2001. PMID: 11294039 Review. French. - Brain NMDA Receptors in Schizophrenia and Depression.
Adell A. Adell A. Biomolecules. 2020 Jun 23;10(6):947. doi: 10.3390/biom10060947. Biomolecules. 2020. PMID: 32585886 Free PMC article. Review.
Cited by
- Behavioral effects of ketamine and toxic interactions with psychostimulants.
Hayase T, Yamamoto Y, Yamamoto K. Hayase T, et al. BMC Neurosci. 2006 Mar 16;7:25. doi: 10.1186/1471-2202-7-25. BMC Neurosci. 2006. PMID: 16542420 Free PMC article. - Glutaminase-deficient mice display hippocampal hypoactivity, insensitivity to pro-psychotic drugs and potentiated latent inhibition: relevance to schizophrenia.
Gaisler-Salomon I, Miller GM, Chuhma N, Lee S, Zhang H, Ghoddoussi F, Lewandowski N, Fairhurst S, Wang Y, Conjard-Duplany A, Masson J, Balsam P, Hen R, Arancio O, Galloway MP, Moore HM, Small SA, Rayport S. Gaisler-Salomon I, et al. Neuropsychopharmacology. 2009 Sep;34(10):2305-22. doi: 10.1038/npp.2009.58. Epub 2009 Jun 10. Neuropsychopharmacology. 2009. PMID: 19516252 Free PMC article. - On the detection of cerebral metabolic depression in experimental traumatic brain injury using Chemical Exchange Saturation Transfer (CEST)-weighted MRI.
Tu TW, Ibrahim WG, Jikaria N, Munasinghe JP, Witko JA, Hammoud DA, Frank JA. Tu TW, et al. Sci Rep. 2018 Jan 12;8(1):669. doi: 10.1038/s41598-017-19094-z. Sci Rep. 2018. PMID: 29330386 Free PMC article. - Potential Roles for the GluN2D NMDA Receptor Subunit in Schizophrenia.
Vinnakota C, Hudson MR, Jones NC, Sundram S, Hill RA. Vinnakota C, et al. Int J Mol Sci. 2023 Jul 23;24(14):11835. doi: 10.3390/ijms241411835. Int J Mol Sci. 2023. PMID: 37511595 Free PMC article. Review. - Dissociable effects of antipsychotics on ketamine-induced changes in regional oxygenation and inter-regional coherence of low frequency oxygen fluctuations in the rat.
Li J, Ishiwari K, Conway MW, Francois J, Huxter J, Lowry JP, Schwarz AJ, Tricklebank M, Gilmour G. Li J, et al. Neuropsychopharmacology. 2014 Jun;39(7):1635-44. doi: 10.1038/npp.2014.10. Epub 2014 Jan 20. Neuropsychopharmacology. 2014. PMID: 24442094 Free PMC article.