Methamphetamine binge administration during late adolescence induced enduring hippocampal cell damage following prolonged withdrawal in rats.
NeuroToxicology. 2018-05-01; 66: 1-9
DOI: 10.1016/j.neuro.2018.02.016
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García-Cabrerizo R(1), Bis-Humbert C(1), García-Fuster MJ(2).
Author information:
(1)IUNICS, University of the Balearic Islands, Palma, Spain; Balearic Islands
Health Research Institute (IdISBa), Palma, Spain.
(2)IUNICS, University of the Balearic Islands, Palma, Spain; Balearic Islands
Health Research Institute (IdISBa), Palma, Spain. Electronic address:
.
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.
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