Individual differences in the hotplate test and effects of habituation on sensitivity to morphine.
Hotplate studies rarely match subjects into groups and often use high temperatures that are less sensitive to the effects of mild analgesics. Subjects may not be matched into groups because it has not been clearly demonstrated that there are reliable and robust individual differences in performance on the hotplate, and out of concern that the testing required to match subjects into groups might reduce the sensitivity of the task to mild analgesics by producing 'behavioral tolerance'. Higher hotplate temperatures may be preferred because they reduce variability in response latencies, and it may be assumed that this precludes the need to match subjects into groups. The results of the present study demonstrate that there are reliable and robust differences among individuals tested on the hotplate, regardless of whether the hotplate is 50 degrees C or 55 degrees C (alpha's > 0.90). The present results also confirm that lower hotplate temperatures are much more sensitive to the effects of mild analgesics: increased response latencies following a low dose of morphine (3 mg/kg) could be reliably detected with only 8 rats at 50 degrees C, while the same dose would not be detected reliably at 55 degrees C unless more than 55 rats were tested. Finally, there was no evidence that habituation to the hotplate produced 'behavioral tolerance' or reduced the sensitivity of the test to the effects of morphine. These findings suggest that hotplate studies should match subjects into groups and use lower hotplate temperatures in order to increase the sensitivity of the test, but also out of an ethical obligation to minimize the intensity of the noxious stimulus and the number of animals exposed to it.
Plone
M A
MA
Cyto Therapeutics Inc., Providence, RI 02906, USA.
Emerich
D F
DF
Lindner
M D
MD
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004361:Drug Tolerance; D006185:Habituation, Psychophysiologic; D006358:Hot Temperature; D007206:Individuality; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects*; D011594:Psychometrics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects*; D013696:Temperature
D000701:Analgesics, Opioid; D009020:Morphine