EFFECTS OF MORPHINE AND NALOXONE ON BEHAVIOR IN THE HOT PLATE TEST - AN ETHOPHARMACOLOGICAL STUDY IN THE RAT

The objectives of this study were: i) to analyse the effects of morphi ne and naloxone on the rat's behaviour in the hot plate test using an ethological approach, and ii) to compare the effectiveness of repeated versus single test paradigms. Animals received either morphine (0, 3, 6 or 9 mg/kg SC) or naloxone (0, 0.01, 0.1 or 1 mg/kg SC). For repeat ed hot plate measures, rats were tested before and 60, 120, 180 and 24 0 min following morphine treatment, as well as 30, 60, 90 and 120 min after naloxone injection. For the single test schedule, rats were test ed only once 60 min after morphine or 30 min after naloxone administra tion, or at 60, 120, 180, 240 and 300 min after 9 mg/kg morphine treat ment. Behaviour was videotaped and analysed by an ethogram and etholog ical techniques. A cluster analysis revealed that the most frequently displayed patterns could be categorised into exploratory sniffing reac tions (walk-sniff, immobile-sniff) and noxious-evoked elements, includ ing primary (paw-licking, stamping), escape (jumping, leaning posture) and independent (hindleg-withdrawal) patterns. During repeated tests, morphine treatment induced: i) a maximum hypoalgesic effect 60 min po st-injection (noxious-evoked patterns were significantly reduced), and ii) an unexpected ''thermal hyperreactivity rebound effect'' after 12 0 min (paw-licking and hindleg-withdrawal were enhanced), although cha nges in hindpaw-licking are more indicative of a hyperalgesic rebound effect. Most changes were quite similar during the single test schedul e at 60 and 120 min after morphine injection. With regard to naloxone treatment, jumping latency was significantly decreased during the repe ated test schedule, but not on single exposure to the plate. Other ele ments were facilitated, however, in the single test (stamping, leaning posture, hindleg-withdrawal). The results indicated that both repeate d and single tests paradigms are of value for testing the effects of m orphine and naloxone on rats. However, under our conditions the single test paradigm gave a better picture of the overall effects of the dru g. Learning as well as habituation and sensitization may mask certain effects during repeated tests. In conclusion, an ethological analysis of the rat's behaviour in the hot plate test following administration of morphine and naloxone has been validated in this study.