Methamphetamine binge administration during late adolescence induced enduring hippocampal cell damage following prolonged withdrawal in rats.

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dc.contributor.author García-Cabrerizo, R.
dc.contributor.author Bis-Humbert, C.
dc.contributor.author García-Fuster, M.J.
dc.date.accessioned 2019-11-13T08:01:22Z
dc.identifier.uri http://hdl.handle.net/11201/150289
dc.description.abstract [eng] A recent study from our laboratory demonstrated that binge methamphetamine induced hippocampal cell damage (i.e., impaired cell genesis) in rats when administered specifically during late adolescence (postnatal day, PND 54-57) and evaluated 24 h later (PND 58). The results also suggested a possible role for brain-derived neurotrophic factor (BDNF) regulating cell genesis and survival. This subsequent study evaluated whether these effects persisted in time as measured following prolonged withdrawal. Male Sprague-Dawley rats were treated (i.p.) with BrdU (2 × 50 mg/kg, 3 days, PND 48-50) followed by a binge paradigm (3 pulses/day, every 3 h, 4 days, PND 54-57) of methamphetamine (5 mg/kg, n = 14, M) or saline (0.9% NaCl, 1 ml/kg, n = 12, C). Following 34 days of forced withdrawal (PND 91), rats were killed 45 min after a challenge dose of saline (Sal: C-Sal, n = 6; M-Sal, n = 7) or methamphetamine (Meth: C-Meth, n = 6; M-Meth, n = 7). Neurogenesis markers (Ki-67: cell proliferation; NeuroD: early neuronal survival; BrdU: prolonged cell survival, 41-43 days old cells) were evaluated by immunohistochemistry while neuroplasticity markers (BDNF and Fos forms) were evaluated by Western blot. The main results showed that a history of methamphetamine administration (PND 54-57) induced enduring hippocampal cell damage (i.e., observed on PND 91) by decreasing cell survival (BrdU + cells) and mature-BDNF (m-BDNF) protein content, associated with neuronal survival, growth and differentiation. Interestingly, m-BDNF regulation paralleled hippocampal c-Fos protein content, indicating decreased neuronal activity, and thus reinforcing the persisting negative effects induced by methamphetamine in rat hippocampus following prolonged withdrawal.
dc.format application/pdf
dc.relation.isformatof Versió postprint del document publicat a: https://doi.org/10.1016/j.neuro.2018.02.016
dc.relation.ispartof Neurotoxicology, 2018, vol. 66, p. 1-9
dc.subject.classification 57 - Biologia
dc.subject.other 57 - Biological sciences in general
dc.title Methamphetamine binge administration during late adolescence induced enduring hippocampal cell damage following prolonged withdrawal in rats.
dc.type info:eu-repo/semantics/article
dc.type info:eu-repo/semantics/acceptedVersion
dc.date.updated 2019-11-13T08:01:22Z
dc.date.embargoEndDate info:eu-repo/date/embargoEnd/2026-12-31
dc.embargo 2026-12-31
dc.subject.keywords Methamphetamine
dc.subject.keywords Withdrawal
dc.subject.keywords Neurotoxicity
dc.subject.keywords neurogenesis
dc.subject.keywords Neuroplasticity
dc.rights.accessRights info:eu-repo/semantics/embargoedAccess
dc.identifier.doi https://doi.org/10.1016/j.neuro.2018.02.016


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