BACKGROUND: Chronic abuse of methamphetamine produces deficits in hippocampal function, perhaps by altering hippocampal neurogenesis and plasticity. We examined how intravenous methamphetamine self-administration modulates active division, proliferation of late progenitors, differentiation, maturation, survival, and mature phenotype of hippocampal subgranular zone (SGZ) progenitors. METHODS: Adult male Wistar rats were given access to methamphetamine 1 hour twice weekly (intermittent short), 1 hour daily (short), or 6 hours daily (long). Rats received one intraperitoneal injection of bromodeoxyuridine (BrdU) to label progenitors in the synthesis (S) phase, and 28-day-old surviving BrdU-immunoreactive (IR) cells were quantified. Ki-67, doublecortin (DCX), and activated caspase-3 (AC-3) were used to visualize and quantify proliferating, differentiating, maturing, and apoptotic cells. Terminal corticosterone was measured to determine changes in adrenal steroids. RESULTS: Intermittent access to methamphetamine increased Ki-67 and DCX-IR cells, but opposing effects on late progenitors and postmitotic neurons resulted in no overall change in neurogenesis. Daily access to methamphetamine decreased all studied aspects of neurogenesis and reduced hippocampal granule neurons and volume, changes that likely are mediated by decreased proliferative and neurogenic capacity of the SGZ. Furthermore, methamphetamine self-administration relative to the amount of methamphetamine intake produced a biphasic effect on hippocampal apoptosis and reduced corticosterone levels. CONCLUSIONS: Intermittent (occasional access) and daily (limited and extended access) self-administration of methamphetamine impact different aspects of neurogenesis, the former producing initial pro-proliferative effects and the latter producing downregulating effects. These findings suggest that altered hippocampal integrity by even modest doses of methamphetamine could account for pronounced pathology linked to methamphetamine abuse.
BACKGROUND: Chronic abuse of methamphetamine produces deficits in hippocampal function, perhaps by altering hippocampal neurogenesis and plasticity. We examined how intravenous methamphetamine self-administration modulates active division, proliferation of late progenitors, differentiation, maturation, survival, and mature phenotype of hippocampal subgranular zone (SGZ) progenitors. METHODS: Adult male Wistar rats were given access to methamphetamine 1 hour twice weekly (intermittent short), 1 hour daily (short), or 6 hours daily (long). Rats received one intraperitoneal injection of bromodeoxyuridine (BrdU) to label progenitors in the synthesis (S) phase, and 28-day-old surviving BrdU-immunoreactive (IR) cells were quantified. Ki-67, doublecortin (DCX), and activated caspase-3 (AC-3) were used to visualize and quantify proliferating, differentiating, maturing, and apoptotic cells. Terminal corticosterone was measured to determine changes in adrenal steroids. RESULTS: Intermittent access to methamphetamine increased Ki-67 and DCX-IR cells, but opposing effects on late progenitors and postmitotic neurons resulted in no overall change in neurogenesis. Daily access to methamphetamine decreased all studied aspects of neurogenesis and reduced hippocampal granule neurons and volume, changes that likely are mediated by decreased proliferative and neurogenic capacity of the SGZ. Furthermore, methamphetamine self-administration relative to the amount of methamphetamine intake produced a biphasic effect on hippocampal apoptosis and reduced corticosterone levels. CONCLUSIONS: Intermittent (occasional access) and daily (limited and extended access) self-administration of methamphetamine impact different aspects of neurogenesis, the former producing initial pro-proliferative effects and the latter producing downregulating effects. These findings suggest that altered hippocampal integrity by even modest doses of methamphetamine could account for pronounced pathology linked to methamphetamine abuse.
Authors: B Czéh; T Michaelis; T Watanabe; J Frahm; G de Biurrun; M van Kampen; A Bartolomucci; E Fuchs Journal: Proc Natl Acad Sci U S A Date: 2001-10-02 Impact factor: 11.205
Authors: Henriette van Praag; Alejandro F Schinder; Brian R Christie; Nicolas Toni; Theo D Palmer; Fred H Gage Journal: Nature Date: 2002-02-28 Impact factor: 69.504
Authors: M Julia García-Fuster; Shelly B Flagel; S Taha Mahmood; Leah M Mayo; Robert C Thompson; Stanley J Watson; Huda Akil Journal: Neuropsychopharmacology Date: 2011-07-27 Impact factor: 7.853
Authors: Timothy W Whitfield; Joel E Schlosburg; Sunmee Wee; Adam Gould; Olivier George; Yanabel Grant; Eva R Zamora-Martinez; Scott Edwards; Elena Crawford; Leandro F Vendruscolo; George F Koob Journal: J Neurosci Date: 2015-03-11 Impact factor: 6.167
Authors: Alexander J Engelmann; Mark B Aparicio; Airee Kim; Jeffery C Sobieraj; Clara J Yuan; Yanabel Grant; Chitra D Mandyam Journal: Brain Struct Funct Date: 2013-02-27 Impact factor: 3.270
Authors: I K Tulloch; L Afanador; L Baker; D Ordonez; H Payne; I Mexhitaj; E Olivares; A Chowdhury; J A Angulo Journal: Neurotox Res Date: 2014-02-19 Impact factor: 3.911
Authors: Irina N Krasnova; Zuzana Justinova; Bruce Ladenheim; Subramaniam Jayanthi; Michael T McCoy; Chanel Barnes; John E Warner; Steven R Goldberg; Jean Lud Cadet Journal: PLoS One Date: 2010-01-20 Impact factor: 3.240