FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2784673699> ?p ?o ?g. }

• W2784673699 endingPage "2042" @default.
• W2784673699 startingPage "2029" @default.
• W2784673699 abstract "Abstinence from methamphetamine addiction enhances proliferation and differentiation of neural progenitors and increases adult neurogenesis in the dentate gyrus (DG). We hypothesized that neurogenesis during abstinence contributes to context-driven drug-seeking behaviors. To test this hypothesis, the pharmacogenetic rat model (GFAP-TK rats) was used to conditionally and specifically ablate neurogenesis in the DG. Male GFAP-TK rats were trained to self-administer methamphetamine or sucrose and were administered the antiviral drug valganciclovir (Valcyte) to produce apoptosis of actively dividing GFAP type 1 stem-like cells to inhibit neurogenesis during abstinence. Hippocampus tissue was stained for Ki-67, NeuroD, and DCX to measure levels of neural progenitors and immature neurons, and was stained for synaptoporin to determine alterations in mossy fiber tracts. DG-enriched tissue punches were probed for CaMKII to measure alterations in plasticity-related proteins. Whole-cell patch-clamp recordings were performed in acute brain slices from methamphetamine naive (controls) and methamphetamine experienced animals (+/-Valcyte). Spontaneous EPSCs and intrinsic excitability were recorded from granule cell neurons (GCNs). Reinstatement of methamphetamine seeking enhanced autophosphorylation of CaMKII, reduced mossy fiber density, and induced hyperexcitability of GCNs. Inhibition of neurogenesis during abstinence prevented context-driven methamphetamine seeking, and these effects correlated with reduced autophosphorylation of CaMKII, increased mossy fiber density, and reduced the excitability of GCNs. Context-driven sucrose seeking was unaffected. Together, the loss-of-neurogenesis data demonstrate that neurogenesis during abstinence assists with methamphetamine context-driven memory in rats, and that neurogenesis during abstinence is essential for the expression of synaptic proteins and plasticity promoting context-driven drug memory.SIGNIFICANCE STATEMENT Our work uncovers a mechanistic relationship between neurogenesis in the dentate gyrus and drug seeking. We report that the suppression of excessive neurogenesis during abstinence from methamphetamine addiction by a confirmed phamacogenetic approach blocked context-driven methamphetamine reinstatement and prevented maladaptive changes in expression and activation of synaptic proteins and basal synaptic function associated with learning and memory in the dentate gyrus. Our study is the first to demonstrate an interesting and dysfunctional role of adult hippocampal neurogenesis during abstinence to drug-seeking behavior in animals self-administering escalating amounts of methamphetamine. Together, these results support a direct role for the importance of adult neurogenesis during abstinence in compulsive-like drug reinstatement." @default.
• W2784673699 created "2018-02-02" @default.
• W2784673699 creator A5007498089 @default.
• W2784673699 creator A5014849995 @default.
• W2784673699 creator A5018178903 @default.
• W2784673699 creator A5025912984 @default.
• W2784673699 creator A5041667614 @default.
• W2784673699 creator A5042670875 @default.
• W2784673699 creator A5042946521 @default.
• W2784673699 creator A5053609203 @default.
• W2784673699 creator A5063151112 @default.
• W2784673699 creator A5071217324 @default.
• W2784673699 creator A5089091971 @default.
• W2784673699 date "2018-01-23" @default.
• W2784673699 modified "2023-10-17" @default.
• W2784673699 title "Neurogenesis during Abstinence Is Necessary for Context-Driven Methamphetamine-Related Memory" @default.
• W2784673699 cites W1434936574 @default.
• W2784673699 cites W1535485604 @default.
• W2784673699 cites W1540177567 @default.
• W2784673699 cites W1570708643 @default.
• W2784673699 cites W1573584522 @default.
• W2784673699 cites W1585828943 @default.
• W2784673699 cites W1594067951 @default.
• W2784673699 cites W1670625131 @default.
• W2784673699 cites W173488229 @default.
• W2784673699 cites W1823225248 @default.
• W2784673699 cites W1910377508 @default.
• W2784673699 cites W1932663338 @default.
• W2784673699 cites W1963724707 @default.
• W2784673699 cites W1963940970 @default.
• W2784673699 cites W1966868706 @default.
• W2784673699 cites W1968840425 @default.
• W2784673699 cites W1969766346 @default.
• W2784673699 cites W1970006557 @default.
• W2784673699 cites W1973025447 @default.
• W2784673699 cites W1974960577 @default.
• W2784673699 cites W1978607952 @default.
• W2784673699 cites W1979686013 @default.
• W2784673699 cites W1983038420 @default.
• W2784673699 cites W1994754601 @default.
• W2784673699 cites W1994886004 @default.
• W2784673699 cites W1995792679 @default.
• W2784673699 cites W1996090115 @default.
• W2784673699 cites W1996456984 @default.
• W2784673699 cites W1998294971 @default.
• W2784673699 cites W2000512824 @default.
• W2784673699 cites W2000907890 @default.
• W2784673699 cites W2001515438 @default.
• W2784673699 cites W2002085774 @default.
• W2784673699 cites W2002112050 @default.
• W2784673699 cites W2010928535 @default.
• W2784673699 cites W2011685861 @default.
• W2784673699 cites W2019179420 @default.
• W2784673699 cites W2019888004 @default.
• W2784673699 cites W2022014092 @default.
• W2784673699 cites W2032307875 @default.
• W2784673699 cites W2033952499 @default.
• W2784673699 cites W2035723358 @default.
• W2784673699 cites W2037158512 @default.
• W2784673699 cites W2040903782 @default.
• W2784673699 cites W2042010146 @default.
• W2784673699 cites W2046705260 @default.
• W2784673699 cites W2049275104 @default.
• W2784673699 cites W2050305231 @default.
• W2784673699 cites W2059412338 @default.
• W2784673699 cites W2063707272 @default.
• W2784673699 cites W2064038456 @default.
• W2784673699 cites W2065535725 @default.
• W2784673699 cites W2066848874 @default.
• W2784673699 cites W2067856703 @default.
• W2784673699 cites W2071181288 @default.
• W2784673699 cites W2082683998 @default.
• W2784673699 cites W2084434011 @default.
• W2784673699 cites W2085298636 @default.
• W2784673699 cites W2087847776 @default.
• W2784673699 cites W2089353787 @default.
• W2784673699 cites W2089394861 @default.
• W2784673699 cites W2092201474 @default.
• W2784673699 cites W2098761499 @default.
• W2784673699 cites W2103524361 @default.
• W2784673699 cites W2105179071 @default.
• W2784673699 cites W2115290127 @default.
• W2784673699 cites W2129789527 @default.
• W2784673699 cites W2130169724 @default.
• W2784673699 cites W2135046848 @default.
• W2784673699 cites W2136108338 @default.
• W2784673699 cites W2139450672 @default.
• W2784673699 cites W2148727841 @default.
• W2784673699 cites W2149901479 @default.
• W2784673699 cites W2150357694 @default.
• W2784673699 cites W2151316369 @default.
• W2784673699 cites W2161800657 @default.
• W2784673699 cites W2163239886 @default.
• W2784673699 cites W2166192872 @default.
• W2784673699 cites W2166687069 @default.
• W2784673699 cites W2166759337 @default.
• W2784673699 cites W2194447116 @default.
• W2784673699 cites W2273912701 @default.

• next