Skip to main content
Erschienen in: Brain Structure and Function 4/2019

12.02.2019 | Original Article

Regional elevations in microglial activation and cerebral glucose utilization in frontal white matter tracts of rhesus monkeys following prolonged cocaine self-administration

verfasst von: Hilary R. Smith, Thomas J. R. Beveridge, Susan H. Nader, Michael A. Nader, Linda J. Porrino

Erschienen in: Brain Structure and Function | Ausgabe 4/2019

Einloggen, um Zugang zu erhalten

Abstract

It has been shown that exposure to cocaine can result in neuroinflammatory responses. Microglia, the resident CNS immune cells, undergo a transition to an activated state when challenged. In rodents, and possibly humans, cocaine exposure activates microglia. The goal of this study was to assess the extent and magnitude of microglial activation in rhesus monkeys with an extensive history of cocaine self-administration. Male rhesus monkeys (N = 4/group) were trained to respond on a fixed-interval 3-min schedule of food or 0.3 mg/kg/injection cocaine presentation (30 reinforcers/session) for 300 sessions. At the end of the final session, monkeys were administered 2-[14C]deoxyglucose intravenously and 45 min later euthanized. Brain sections were used for autoradiographic assessments of glucose utilization and for microglia activation with [3H]PK11195, a marker for the microglial 18-kDa translocator protein. There were no group differences in gray matter [3H]PK11195 binding, while binding was significantly greater in cocaine self-administration animals as compared to food controls in 8 of the 11 white matter tracts measured at the striatal level. Binding did not differ from control at other levels. There were also significant increases in white matter local cerebral glucose utilization at the striatal level, which were positively correlated with [3H]PK11195 binding. The present findings demonstrate an elevation in [3H]PK11195 binding in forebrain white matter tracts of nonhuman primates with a prolonged history of cocaine self-administration. These elevations were also associated with greater cerebral metabolic rates. These data suggest that white matter deficits may contribute to behavioral, motivational, and cognitive impairments observed in cocaine abusers.
Literatur
Zurück zum Zitat Akira S, Takeda K (2004) Functions of toll-like receptors: lessons from KO mice. C R Biol 327:581–589CrossRefPubMed Akira S, Takeda K (2004) Functions of toll-like receptors: lessons from KO mice. C R Biol 327:581–589CrossRefPubMed
Zurück zum Zitat Crane AM, Porrino LJ (1989) Adaptation of the quantitative 2-[14C]deoxyglucose method for use in freely moving rats. Brain Res 499:87–92CrossRefPubMed Crane AM, Porrino LJ (1989) Adaptation of the quantitative 2-[14C]deoxyglucose method for use in freely moving rats. Brain Res 499:87–92CrossRefPubMed
Zurück zum Zitat Kuhlmann AC, Guilarte TR (2000) Cellular and subcellular localization of peripheral benzodiazepine receptors after trimethyltin neurotoxicity. J Neurochem 74:1694–1704CrossRefPubMed Kuhlmann AC, Guilarte TR (2000) Cellular and subcellular localization of peripheral benzodiazepine receptors after trimethyltin neurotoxicity. J Neurochem 74:1694–1704CrossRefPubMed
Zurück zum Zitat Lawson LJ, Perry VH, Dri P, Gordon S (1990) Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience 39:151–170CrossRefPubMed Lawson LJ, Perry VH, Dri P, Gordon S (1990) Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience 39:151–170CrossRefPubMed
Zurück zum Zitat Letchworth SR, Nader MA, Smith HR, Friedman DP, Porrino LJ (2001) Progression of changes in dopamine transporter binding site density as a result of cocaine self-administration in rhesus monkeys. J Neurosci 21:2799–2807CrossRefPubMedPubMedCentral Letchworth SR, Nader MA, Smith HR, Friedman DP, Porrino LJ (2001) Progression of changes in dopamine transporter binding site density as a result of cocaine self-administration in rhesus monkeys. J Neurosci 21:2799–2807CrossRefPubMedPubMedCentral
Zurück zum Zitat Lim KO, Choi SJ, Pomara N, Wolkin A, Rotrosen JP (2002) Reduced frontal white matter integrity in cocaine dependence: a controlled diffusion tensor imaging study. Biol Psychiatry 51:890–895CrossRefPubMed Lim KO, Choi SJ, Pomara N, Wolkin A, Rotrosen JP (2002) Reduced frontal white matter integrity in cocaine dependence: a controlled diffusion tensor imaging study. Biol Psychiatry 51:890–895CrossRefPubMed
Zurück zum Zitat Paxinos G, Huang XF, Toga AW (2000) The rhesus monkey brain in stereotaxic coordinates. Academic Press, San Diego Paxinos G, Huang XF, Toga AW (2000) The rhesus monkey brain in stereotaxic coordinates. Academic Press, San Diego
Zurück zum Zitat Porrino LJ, Lyons D, Miller MD, Smith HR, Friedman DP, Daunais JB, Nader MA (2002) Metabolic mapping of the effects of cocaine during the initial phases of self-administration in the nonhuman primate. J Neurosci 22:7687–7694CrossRefPubMedPubMedCentral Porrino LJ, Lyons D, Miller MD, Smith HR, Friedman DP, Daunais JB, Nader MA (2002) Metabolic mapping of the effects of cocaine during the initial phases of self-administration in the nonhuman primate. J Neurosci 22:7687–7694CrossRefPubMedPubMedCentral
Zurück zum Zitat Ren L, Lubrich B, Biber K, Gebicke-Haerter PJ (1999) Differential expression of inflammatory mediators in rat microglia cultured from different brain regions. Brain Res Mol Brain Res 65:198–205CrossRefPubMed Ren L, Lubrich B, Biber K, Gebicke-Haerter PJ (1999) Differential expression of inflammatory mediators in rat microglia cultured from different brain regions. Brain Res Mol Brain Res 65:198–205CrossRefPubMed
Zurück zum Zitat Schmahmann JD, Pandya DN (2006) Fiber pathways of the brain. Oxford University Press, Oxford, New YorkCrossRef Schmahmann JD, Pandya DN (2006) Fiber pathways of the brain. Oxford University Press, Oxford, New YorkCrossRef
Zurück zum Zitat Schmid CD, Sautkulis LN, Danielson PE et al (2002) Heterogeneous expression of the triggering receptor expressed on myeloid cells-2 on adult murine microglia. J Neurochem 83:1309–1320CrossRefPubMedPubMedCentral Schmid CD, Sautkulis LN, Danielson PE et al (2002) Heterogeneous expression of the triggering receptor expressed on myeloid cells-2 on adult murine microglia. J Neurochem 83:1309–1320CrossRefPubMedPubMedCentral
Zurück zum Zitat Sokoloff L, Reivich M, Kennedy C et al (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28:897–916CrossRefPubMed Sokoloff L, Reivich M, Kennedy C et al (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28:897–916CrossRefPubMed
Zurück zum Zitat Staley JK, Mash DC (1996) Adaptive increase in D3 dopamine receptors in the brain reward circuits of human cocaine fatalities. J Neurosci 16:6100–6106CrossRefPubMedPubMedCentral Staley JK, Mash DC (1996) Adaptive increase in D3 dopamine receptors in the brain reward circuits of human cocaine fatalities. J Neurosci 16:6100–6106CrossRefPubMedPubMedCentral
Zurück zum Zitat Stephenson DT, Schober DA, Smalstig EB, Mincy RE, Gehlert DR, Clemens JA (1995) Peripheral benzodiazepine receptors are colocalized with activated microglia following transient global forebrain ischemia in the rat. J Neurosci 15:5263–5274CrossRefPubMedPubMedCentral Stephenson DT, Schober DA, Smalstig EB, Mincy RE, Gehlert DR, Clemens JA (1995) Peripheral benzodiazepine receptors are colocalized with activated microglia following transient global forebrain ischemia in the rat. J Neurosci 15:5263–5274CrossRefPubMedPubMedCentral
Zurück zum Zitat Tanaka K, Nogawa S, Suzuki S, Dembo T, Kosakai A (2003) Upregulation of oligodendrocyte progenitor cells associated with restoration of mature oligodendrocytes and myelination in peri-infarct area in the rat brain. Brain Res 989:172–179CrossRefPubMed Tanaka K, Nogawa S, Suzuki S, Dembo T, Kosakai A (2003) Upregulation of oligodendrocyte progenitor cells associated with restoration of mature oligodendrocytes and myelination in peri-infarct area in the rat brain. Brain Res 989:172–179CrossRefPubMed
Metadaten
Titel
Regional elevations in microglial activation and cerebral glucose utilization in frontal white matter tracts of rhesus monkeys following prolonged cocaine self-administration
verfasst von
Hilary R. Smith
Thomas J. R. Beveridge
Susan H. Nader
Michael A. Nader
Linda J. Porrino
Publikationsdatum
12.02.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Brain Structure and Function / Ausgabe 4/2019
Print ISSN: 1863-2653
Elektronische ISSN: 1863-2661
DOI
https://doi.org/10.1007/s00429-019-01846-4

Weitere Artikel der Ausgabe 4/2019

Brain Structure and Function 4/2019 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Neu im Fachgebiet Neurologie

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.