Pharmacokinetic aspects of naloxone-precipitated morphine withdrawal in male and female prepubertal mice.
It has been shown that the expression of the morphine (MOR) withdrawal syndrome precipitated by naloxone (NAL) is more intense in male mice than in females, but the reasons for this phenomenon remain uncertain. The purpose of the present study was to evaluate whether this sexual dimorphism might be due to differences in MOR and/or NAL plasma levels after a chronic treatment with MOR. Prepubertal Swiss male and female mice were rendered dependent by intraperitoneal (i.p.) injection of MOR (2 mg/kg), twice daily for 9 days. On day 10 dependent mice received NAL (6 mg/kg, i.p.) 60 min after MOR injection. Blood samples were taken at different times in order to determine MOR and NAL plasma levels by gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC), respectively. Pharmacokinetic analysis showed no differences between male and female mice either for MOR or for NAL. In conclusion, although males and females respond differentially to NAL-precipitated withdrawal, this dimorphic behavior would not be influenced by a pharmacokinetic factor.
Diaz
Silvina L
SL
Instituto de Investigaciones Farmacológicas (UBA-CONICET), Buenos Aires, Argentina.
Hermida
María P
MP
Joannas
Leonel D
LD
Olivera
Mónica
M
Ridolfi
Adriana
A
Villaamil
Edda C
EC
Balerio
Graciela N
GN
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009021:Morphine Dependence / Q000097:blood / Q000150:complications; D009270:Naloxone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics; D012737:Sex Factors; D012741:Sexual Maturation; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000378:metabolism*; D013997:Time Factors
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009270:Naloxone; D009020:Morphine