title: Neonatal morphine administration leads to changes in hippocampal BDNF levels and antioxidant enzyme activity in the adult life of rats.
abstract: It is know that repeated exposure to opiates impairs spatial learning and memory and that the hippocampus has important neuromodulatory effects after drug exposure and withdrawal symptoms. Thus, the aim of this investigation was to assess hippocampal levels of BDNF, oxidative stress markers associated with cell viability, and TNF-α in the short, medium and long term after repeated morphine treatment in early life. Newborn male Wistar rats received subcutaneous injections of morphine (morphine group) or saline (control group), 5 μg in the mid-scapular area, starting on postnatal day 8 (P8), once daily for 7 days, and neurochemical parameters were assessed in the hippocampus on postnatal days 16 (P16), 30 (P30), and 60 (P60). For the first time, we observed that morphine treatment in early life modulates BDNF levels in the medium and long term and also modulates superoxide dismutase activity in the long term. In addition, it was observed effect of treatment and age in TNF-α levels, and no effects in lactate dehydrogenase levels, or cell viability. These findings show that repeated morphine treatment in the neonatal period can lead to long-lasting neurochemical changes in the hippocampus of male rats, and indicate the importance of cellular and intracellular adaptations in the hippocampus after early-life opioid exposure to tolerance, withdrawal and addiction.
authors.affiliation: Pain Pharmacology and Neuromodulation Laboratory: Animal Models, Department of Pharmacology, Institute of Basic Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Rua Sarmento Leite, 500 sala 202, Porto Alegre, RS, 90050-170, Brazil.
authors.forename: J R
authors.initials: JR
authors.lastname: Rozisky
authors.forename: G
authors.initials: G
authors.lastname: Laste
authors.forename: I C
authors.initials: IC
authors.lastname: de Macedo
authors.forename: V S
authors.initials: VS
authors.lastname: Santos
authors.forename: R
authors.initials: R
authors.lastname: Krolow
authors.forename: C
authors.initials: C
authors.lastname: Noschang
authors.forename: C
authors.initials: C
authors.lastname: Vanzella
authors.forename: K
authors.initials: K
authors.lastname: Bertoldi
authors.forename: G A
authors.initials: GA
authors.lastname: Lovatel
authors.forename: I C C
authors.initials: IC
authors.lastname: de Souza
authors.forename: I R
authors.initials: IR
authors.lastname: Siqueira
authors.forename: C
authors.initials: C
authors.lastname: Dalmaz
authors.forename: W
authors.initials: W
authors.lastname: Caumo
authors.forename: I L S
authors.initials: IL
authors.lastname: Torres
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D014409:Tumor Necrosis Factor-alpha; D009020:Morphine; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase