Morphine-induced behavioral disruption in rats chronically depleted of brain dopamine

The ability of rats, chronically depleted of brain dopamine (DA), to develop tolerance to morphine (120 mg/kg, s.c.) given twice daily was studied using a food-reinforced operant procedure (FR-10). DA was depleted via the administration of 6-OHDA (150 ug, ict.) and desmethylimipramine (DMI; 25 mg/kg, ip.) to rats 14 days of age. This procedure resulted in a 61% depletion of brain DA when these rats were 120 days of age, while norepinephrine levels were not significantly affected. The response rates of DA-depleted and vehicle (ict.) + DMI treated controls were equally suppressed by various acute doses of morphine, but the DA-depleted group appeared to develop tolerance to the higher morphine dosage regimen (120 mg/kg, b.i.d) faster than the control group. In addition, DA-depleted rats exhibited a greater suppression of response rates 24 hr after the cessation of morphine treatment.