title: The long-term effects of neonatal morphine administration on the pentylenetetrazol seizure model in rats: the role of hippocampal cholinergic receptors in adulthood.
abstract: Early life exposure to opiates may affect neuropathological conditions, such as epilepsy, during adulthood. We investigated whether neonatal morphine exposure affects pentylenetetrazol (PTZ)-induced seizures in adulthood. Male rats were subcutaneously injected with morphine or saline on postnatal days 8-14. During adulthood, each rat was assigned to 1 of the following 10 sub-groups: saline, nicotine (0.1, 0.5, or 1 μg), atropine (0.25 or 1 μg), oxotremorine M (0.1 or 1 μg), or mecamylamine (2 or 8 μg). An intrahippocampal infusion of the indicated compound was administered 30 min before seizure induction (80 mg/kg PTZ). Compared with the saline/oxotremorine (1 μg), saline/saline, and morphine/saline groups, the morphine/oxotremorine (1 μg) group showed a significantly increased latency to the first epileptic behavior. The duration of tonic-clonic seizures was significantly lower in the morphine/oxotremorine (1 μg) group compared to the saline/saline and morphine/saline groups. The severity of seizure was significantly decreased in the morphine/atropine (1 μg) group than in the saline/atropine (1 μg). Seizure severity was also decreased in the morphine/mecamylamine (2 μg) group than in the saline/mecamylamine (2 μg) group. Latency for death was significantly lower in the morphine/mecamylamine (2 μg) group compared with the saline/mecamylamine (2 μg) group. Mortality rates in the morphine/atropine (1 μg) and morphine/mecamylamine (2 μg) groups were significantly lower than those in the saline/atropine (1 μg) and saline/mecamylamine (2 μg) groups, respectively. Chronic neonatal morphine administration attenuated PTZ-induced seizures, reduced the mortality rate, and decreased the impact of the hippocampal cholinergic system on seizures and mortality rate in adult rats. Neonatal morphine exposure induces changes to μ-receptors that may lead to activation of GABAergic neurons in the hippocampus. This pathway may explain the anti-convulsant effects of morphine observed in our study.
authors.affiliation: Faculty of Medicine, Department of Physiology, Neurophysiology Research Center, Urmia University of Medical Sciences, Urmia, Iran.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Saboory
authors.forename: Morteza
authors.initials: M
authors.lastname: Gholami
authors.forename: Samad
authors.initials: S
authors.lastname: Zare
authors.forename: Shiva
authors.initials: S
authors.lastname: Roshan-Milani
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D010433:Pentylenetetrazole; D051381:Rats; D017208:Rats, Wistar; D011950:Receptors, Cholinergic / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D011950:Receptors, Cholinergic; D009020:Morphine; D010433:Pentylenetetrazole
keywords: cholinergic receptors; hippocampus; morphine; rat; seizure