Genetic differences in morphine sensitivity, tolerance and withdrawal in rats.
Significant genetic differences in the endogenous opioid system and in response to a variety of noxious stimuli are present in rodents. We now compared the response to noxious heat with the hot plate test, morphine sensitivity and the development of tolerance and dependence to morphine in spontaneously hypertensive (SHR), Wistar-Kyoto (WK) and Sprague-Dawley (SD) rats. Significant differences were observed in basal nociception among the three strains, where SHRs were hypoalgesic compared to WK and SD. The antinociceptive effect of morphine varied among strains (SD>SHR>WK) as did the rate of tolerance development (10 mg/kg morphine 2/day for 4 days) where WK>SD=SHR. SHR rats developed hyperalgesia following morphine administration during the course of tolerance development. Furthermore, although naloxone (2 mg/kg) precipitated withdrawal symptoms in all tolerant rats, the panorama of symptoms varied among the three strains. Thus, there are significant genetic differences in a variety of effect of opiates.
Hoffmann
O
O
Department of Medical Laboratory Sciences and Technology, Division of Clinical Neurophysiology, Huddinge University Hospital, S-141 86 Huddinge, Sweden.
Plesan
A
A
Wiesenfeld-Hallin
Z
Z
D000818:Animals; D004351:Drug Resistance / Q000235:genetics; D004361:Drug Tolerance / Q000235:genetics; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics; D011921:Rats, Inbred WKY / Q000235:genetics; D017207:Rats, Sprague-Dawley / Q000235:genetics; D012684:Sensory Thresholds / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000235:genetics*; D013697:Thermosensing / Q000187:drug effects / Q000502:physiology
D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D009020:Morphine