ABSTRACT
After 60 days of treating both sexes with daily oral doses of 15 mg/kg methadone hydrochloride, Wistar rats were mated. Drug treatment of females continued until the weaning of their pups. The body weight of pups was reduced compared to controls up to weaning, and viability was significantly decreased. Ontogeny of reflexes was delayed, and exploration in an open-field arena was reduced up to 2 weeks of age, but then increased above controls. Defecation in the open-field arena was lessened. When only the sire received methadone, only the increase in exploratory behavior and the decrease in defecation occurred. Breeding offspring (F1) of which both parents had methadone treatment gave F2 generation offspring for which neonatal mortality was significantly elevated and defecation in the open-field arena was lessened at 21 days. No changes clearly traceable to methadone were found in the subsequent F3 generation. Some F3 generation rats were treated with methadone and bred in the same manner as the original parental generation. The resulting pups, having the genealogy twice-exposed to methadone, were not significantly different from those whose immediate parents only received the drug.
Subject(s)
Behavior, Animal/drug effects , Growth Disorders/chemically induced , Growth/drug effects , Methadone/adverse effects , Reproduction/drug effects , Animals , Birth Weight/drug effects , Body Weight/drug effects , Brain/growth & development , Female , Growth Disorders/genetics , Humans , Lactation/drug effects , Male , Methadone/pharmacology , Organ Size/drug effects , Pedigree , Pregnancy , Pregnancy, Animal/drug effects , Rats , Rats, Inbred StrainsABSTRACT
The changes in effects on motor activity of rats upon repeated (48 day) dosing with four narcotic analgesics were determined. The following were administered IP once daily in a.m.: morphine sulfate (MOR), 20 mg/kg: dl-methadone HCl (MET), 5 mg/kg: meperidine HCl (MEP), 10 mg/kg; and pentazocine lactate (PEN), 20 mg/kg. Motility was measured in photocell actometers every 4 days for 6 hr after dosing. Activity was elevated after the initial dose as follows: for MOR at hours 3-5, for MET at hours 2-5, for MEP and PEN at hours 2-3. Time of peak response showed no systematic change over days. For all 4 drugs there occurred, upon repeated dosing, a considerable increase in motility over the initial acute response. For MOR the greatest increment occurred between days 12 and 16, but regression analysis showed a strong linear trend of increasing activity from day 1 through day 48. For MET and MEP, activity rose considerably between days 4 and 12 to a maximum, after which the activity trended downward for MET, but showed no continuing fall or climb for MEP. For PEN the greatest increases were from days 4 to 8 and 44 to 48, with an intervening period of relative stability. These results seem to be more readily explainable in terms of increasing sensitivity to the motor excitatory actions of these agents than merely by a development of tolerance to motor-inhibitory actions.
