Chronomodulation of withdrawal signs in morphine-dependent rats

Male Sprague-Dawley rats (200-250 g) were segregated into 12 groups (n=5). Six groups were injected with morphine sulphate (10,20,30,50 mg/kg,ip) on days 1, 2, 3 and 4 respectively. The specified dose of morphine was given in two divided doses daily at 1000 h (light) and 2200 h (dark) for four consecutive days. The remaining six groups received saline. On day 5, the rats from saline and morphine treated groups were injected with naloxone (50 mg/kg, ip) at 0600 h, 1000 h, 1400 h, 1800 h, 2200 h, or 0200 h to precipitate the withdrawal signs during the light and dark phases of the 24 h period. Withdrawal signs were monitored for the following 30 min. Diarrhea, tremor, teeth chattering and crying (vocalization) were exhibited exclusively by the morphine-dependent rats. Escape attempts and restless activity were observed mostly in morphine-dependent groups, except for a limited response by controls at 0200 h or 0600 h. The percentage response of other signs such as hunch-back posture, piloerection, stereotypic jumping, urination and salivation in morphine-treated groups was significantly higher than controls (p<0.05). Manifestation of these signs of morphine withdrawal over a 24 h light-dark cycle is addressed.