Saboory_2014_Dev.Psychobiol_56_498

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 mug), atropine (0.25 or 1 mug), oxotremorine M (0.1 or 1 mug), or mecamylamine (2 or 8 mug). An intrahippocampal infusion of the indicated compound was administered 30 min before seizure induction (80mg/kg PTZ). Compared with the saline/oxotremorine (1 mug), saline/saline, and morphine/saline groups, the morphine/oxotremorine (1 mug) 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 mug) group compared to the saline/saline and morphine/saline groups. The severity of seizure was significantly decreased in the morphine/atropine (1 mug) group than in the saline/atropine (1 mug). Seizure severity was also decreased in the morphine/mecamylamine (2 mug) group than in the saline/mecamylamine (2 mug) group. Latency for death was significantly lower in the morphine/mecamylamine (2 mug) group compared with the saline/mecamylamine (2 mug) group. Mortality rates in the morphine/atropine (1 mug) and morphine/mecamylamine (2 mug) groups were significantly lower than those in the saline/atropine (1 mug) and saline/mecamylamine (2 mug) 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 mu-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. (c) 2013 Wiley Periodicals, Inc. Dev Psychobiol 56: 498-509, 2014.