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.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D003216:Conditioning, Operant / Q000187:drug effects*; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D004361:Drug Tolerance; D006801:Humans; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D012055:Reinforcement Schedule; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D013997:Time Factors
D006892:Hydroxydopamines; D009020:Morphine; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine