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Using novelty-induced grooming as a marker of stress response and clonidine as an anti-stress drug, present study tested the hypothesis that intermittent injection of morphine may induce stress and allow some withdrawal during each interval (Houshyar et al. 2003). Male Wistar rats were injected s.c. with saline or morphine twice daily (08:30 and 18:30) for 4 days with increasing doses (10, 20, 30, 40 mg/kg/injection/day). On days 1–4, animals were given tap water with or without 5 μg/ml clonidine (18:30–8:30). On day 5, at the time of morning injections, animals were observed for 5 minutes for grooming and spontaneous withdrawal [14-h withdrawal assessed with global withdrawal score (GWS)]. Then, animals were injected s.c. with morphine (40 mg/kg) or saline and 2 hours later with naloxone (1 mg/kg) and observed for 15 minutes for withdrawal symptoms. Data were analyzed using ANOVA and Bonferroni test. Morphine and morphine+clonidine groups spent less time in grooming and produced marked GWS and naloxoneprecipitated withdrawal signs. Present study could not demonstrate an increase in grooming refl ecting stress before the next dose of intermittent use of morphine, but provides evidence that the injection regimen allows manifestations of partial morphine withdrawal. Clonidine, possibly due to insuffi cient water intake, could not prevent withdrawal signs. Further experimentation may provide more data to clarify spontaneous withdrawal associated with the treatment regimen.
Prolonged or repeated seizures have been shown to cause spontaneous recurrent seizures, increased anxiety‑related behavior, locomotor hyperactivity, impaired functions of learning and memory, and neuronal damage in the hippocampus and other brain regions in animals. Mice and rats treated with antimuscarinic drugs after fasting for two days or less develop convulsions after being allowed to eat ad libitum. To address whether such behavioral and neuroanatomic changes occur following these convulsions, mice treated i.p. with saline (control) or 2.4 mg/kg atropine and given food after 24 h of fasting were grouped according to seizure scores for behavioral and histological analysis. Following convulsions, the occurrence of spontaneous recurrent seizures was observed for 30 days. Motor activity and grooming behavior were assessed in the open field, and memory was assessed using the novel object recognition test 4 and 7 days after onset of convulsions, respectively. Animals allocated for the histological analysis were decapitated 7 days after onset of convulsions and hippocampal slices were evaluated for the percentage of degenerating neurons stained with Fluoro‑Jade C. Spontaneous recurrent seizures, locomotor alterations, anxiety‑related behavior, memory impairment, and neuronal loss in the granular layer of the dentate gyrus were not detected in the animals with seizure score 1–2 or 3–5. These results are in accordance with those related to the absence of behavioral changes, cognitive deficits, and hippocampal neuronal damage after single brief seizures in animals and patients with epilepsy.
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