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.
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