Sex differences in development of morphine tolerance and dependence in the rat.
BACKGROUND
Several investigators have shown that male rodents are more sensitive than females to morphine's antinociceptive effects.


OBJECTIVE
The present study was conducted to determine whether this sex difference is stable after chronic morphine treatment.


RESULTS
Acutely administered morphine produced significantly greater hotplate and tail withdrawal antinociception in males than in females. In contrast, there were no sex differences in morphine's hotplate or tail withdrawal effects under repeated (1-week interval) dosing conditions. In a separate group of rats, after 2 weeks of twice-daily morphine treatment (10-20 mg/kg per injection), the ED50 for morphine's antinociceptive effects increased approximately 6.9-fold in males versus only 3.7-fold in females; chronic morphine treatment also disrupted the estrous cycle of females. In a separate group of rats treated with 10 mg/kg morphine twice daily for 5 days, treatment with naloxone (1.0 mg/kg) on day 6 produced greater withdrawal scores in males than in females.


CONCLUSIONS
These experiments demonstrate sex differences in development of tolerance to and dependence on morphine in the rat.
Craft
R M
RM
Department of Psychology, Washington State University, Pullman 99164-4820, USA. craft@wsunix.wsu.edu
Stratmann
J A
JA
Bartok
R E
RE
Walpole
T I
TI
King
S J
SJ
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004971:Estrus / Q000502:physiology; D005260:Female; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000503:physiopathology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D013997:Time Factors
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009270:Naloxone; D009020:Morphine