Physical dependence in the rat induced by slow release morphine: dose-response, time course and brain biogenic amines.

1. Physical dependence was induced in rats by administration of a slow release morphine emulsion (morphine SR), and assessed by scoring abstinence signs and temperature changes after i.p. administration of naloxone (5 mg/kg). Three groups of rats received doses of 75, 100 or 150 mg/kg of morphine SR. Dependence was evaluated in each of these groups after 24, 48 and 72 h. 2. The effect of these treatments at the different times on brain levels of serotonin, 5-hydroxyindoleacetic acid, noradrenaline and dopamine was determined. 3. A ceiling level of dependence was reached 24 h after 75 and 100 mg/kg and 48 h after 150 mg/kg of morphine SR. 4. These different treatments produced no significant effect on the brain levels of noradrenaline, dopamine or serotonin. The levels of 5-hydroxyindoleacetic acid were significantly raised in morphine-dependent rats and the changes correlated well with the changes in abstinence behaviour and temperature after naloxone. 5. The results suggest that a relationship exists between serotonin turnover and physical dependence on morphine.