Demonstration of physical dependence following chronic continuous methadone delivery via osmotic minipumps in pregnant rats.

Abstract:

:The effects of a 14-day (gestation days 7-20) chronic methadone (6.3-9.0 mg/kg/day) infusion via osmotic minipumps were studied on the induction of physical dependence in both pregnant and nonpregnant female rats. Following continued methadone exposure, an acute injection of naloxone (2.0 mg/kg, SC) produced the following symptoms of withdrawal in both pregnant and nonpregnant methadone-exposed rats: increased frequency of head shakes, teeth-chattering and face-rubbing episodes, as well as the induction of burrowing, diarrhea, facial tremor, squeaking and vaginal sniffing. Increased fetal movement in the maternal abdomen was also observed in the pregnant rats. In the saline-exposed pregnant controls, naloxone failed to induce a significant effect. In addition, brain and plasma methadone levels during the various stages of pregnancy (gestation days 8-20) were determined. The methadone levels in plasma were initially variable (gestation days 8-12) but became more constant (approximately 50 ng/ml) from gestation day 14 to 20. Methadone brain levels also followed a similar pattern, except that the brain methadone content was at least 20-fold greater than plasma concentrations at any given time. Thus, relative to the high brain levels, the present data suggest that acute changes in methadone plasma concentration may not be a good index of pharmacological effect.

journal_name

Neurotoxicol Teratol

authors

Darmani NA,Saady JJ,Schnoll SH,Martin BR

doi

10.1016/0892-0362(91)90046-y

subject

Has Abstract

pub_date

1991-11-01 00:00:00

pages

627-30

issue

6

eissn

0892-0362

issn

1872-9738

journal_volume

13

pub_type

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