Abstract
These experiments examined the effects of a benzodiazepine (midazolam) on rats' sensitivity-reactivity to the heated floor of a hot-plate apparatus. Rats were either previously exposed to the heated floor, or naive to the hot-plate apparatus, while control rats were familiarized with the apparatus in the absence of pain. A low dose (0.63 or 1.25 mg/kg) of midazolam attenuated the conditioned hypoalgesic response resulting from pre-exposure to a heated floor, but did not affect the hypoalgesic response elicited by exposure to a novel hot-plate apparatus nor the “baseline” sensitivity-reactivity among control rats. A high dose (2.5 mg/kg) of midazolam resulted in a naloxone-insensitive increase in both the conditioned and the novelty-induced hypoalgesia, and provoked a small, but naloxone-reversible increase in paw-lick latencies among control rats. The results were taken to mean that exposure to the heated floor results in hypoalgesic responses as a consequence of fear conditioning and the reinstatement of novelty. Midazolam was assumed to attenuate conditioned hypoalgesia by reducing fear but at the high dose to augment the hypoalgesic effects of novelty.
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References
Bardo MT, Hughes RA (1979) Exposure to a nonfunctional hot-plate as a factor in the assessment of morphine-induced analgesia and analgesic tolerance in rats. Pharmacol Biochem Behav 10:481–485
Bolles RC, Fanselow MS (1980) A perceptual-defensive-recuperative model of fear and pain. Behav Brain Sc 3:291–323
Chance WT (1980) Autoanalgesia: opiate and non-opiate mechanisms. Neurosci Biobehav Rev 4:55–67
Chance WT, Krynock GM, Rosecrans JA (1978) Antinociception following lesion-induced hyperemotionality and conditioned fear. Pain 4:234–252
Chance WT, White AC, Krynock GM, Rosecrans JA (1979) Autoanalgesia: Acquisition, blockade and relationship to opiate binding. Eur J Pharmacol 58:461–468
Clavier N, Lombard MC, Besson JM (1992) Benzodiazepines and pain: Effects of midazolam on the activities of nociceptive nonspecific dorsal horn neurons in the rat spinal cord. Pain 48:61–71
Davis M (1979) Diazepam and flurazepam: Effects on conditioned fear as measured with the potentiated startle paradigm. Psychopharmacology 62:1–7
Fanselow MS (1986) Conditioned fear-induced opiate analgesia: A competing motivational state theory of stress analgesia. Ann NY Acad Sci 467:40–54
Fanselow MS, Baackes MP (1982) Conditioned fear-induced opiate analgesia on the formalin test: evidence for two aversive motivational systems. Learn Motiv 13:200–221
Fanselow MS, Helmstetter FJ (1988) Conditional analgesia, defensive freezing, and benzodiazepines. Behav Neurosci 102:233–243
File SE (1980) The use of social interaction as a method for detecting anxiolytic activity of chlordiazepoxide-like drugs. J Neurosci Methods 2:219–238
Foo H, Westbrook RF (1991) Naloxone-induced hypoalgesia: Effects of heat, cold and novelty. Q J Exp Psychol 43B:137–156
Gray JA (1982) The neuropsychology of anxiety: an enquiry into the functions of the septo-hippocampal system. Oxford University Press, Oxford
Greeley JD, Westbrook RF (1990) Some effects of exposure to a heat stressor upon the rat's subsequent reactions to that stressor. Q J Exp Psychol 42B:241–265
Haefely WE (1990) The GABAA-benzodiazepine receptor: biology and pharmacology. In: Burrows GD, Roth M, Noyes Jr (eds) Handbook of anxiety, vol 3: The neurobiology of anxiety. Elsevier, New York
Hays WL (1972) Statistics for the social sciences. Holt, Rinehart and Winston, New York
Kinscheck IB, Watkins LR, Mayer DJ (1984) Fear is not critical to classically conditioned analgesia: the effects of periaqueductal grey lesions and administration of chlordiazepoxide. Brain Res 298:33–44
Lau CE, Falk JL, Tang M (1990) Motor performance decrement by midazolam: antagonism by RO 15-1788 and CGS 8216. Pharmacol Biochem Behav 36:139–143
Maier SF (1990) Diazepam modulation of stress-induced analgesia depends on the type of analgesia. Behav Neurosci 104:339–247
Miczek KA (1973) Effects of scopolamine, amphetamine and benzodiazepines on conditioned suppression. Pharmacol Biochem Behav 1:401–411
Miller RG (1966) Simultaneous statistical inference. McGraw Hill, New York
Niv D, Davidovich S, Geller E, Urca G (1988) Analgesic and hyperalgesic effects of midazolam: Dependence on route of administration. Anesth Analg 67:1169–1173
Nowakowska E, Chodera A (1991) Studies on the involvement of opioid mechanism in the locomotor effects of benzodiazepines in rats. Pharmacol Biochem Behav 38:265–266
Pascoe JP, Gallagher M, Kapp BS (1983) Benzodiazepine effects on heart rate conditioning in the rabbit. Psychopharmacology 79:256–261
Rodger RS (1967) Type II errors and their decision basis. Br J Math Statist Psychol 20:187–204
Ross RT (1985) Blocking and unblocking of conditioned analgesia. Learn and Motiv 16:173–189
Ross RT (1986) Pavlovian second-order conditioned analgesia. J Exp Psychol Anim Behav Proc 12:32–39
Ross RT, Randich A (1985) Associative aspects of conditioned analgesia evoked by a discrete CS Anim Learn Behav 13:419–431
Rushton R, Steinberg H (1966) Combined effects of chlordiazepoxide and dexamphetamine on activity in rats in an unfamiliar environment. Nature 211:1312–1313
Tenen SS (1967) Recovery time as a measure of CER strength: effects of benzodiazepines, amobarbital, chlorpromazine and amphetamine. Psychopharmacologia 12:1–17
Terman GW, Shavit Y, Lewis JW, Cannon JT, Liebeskind JC (1984) Intrinsic mechanisms of pain inhibition: Activation by stress. Science 226:1270–1277
Walsh TJ, McLamb RL, Tilson HA (1986) A comparison of the effects of RO15, 1788 and chlordiazepoxide on hot-plate latencies, acoustic startle, and locomotor activity. Psychopharmacology 88:514–519
Westbrook RF, Greeley JD, Nabke CP, Swinbourne AL (1991a) Aversive conditioning in the rat: Effects of a benzodiazepine and of an opioid agonist and antagonist on conditioned hypoalgesia and fear. J Exp Psychol Anim Behav Proc 17:219–230
Westbrook RF, Greeley JD, Nabke CP, Swinbourne AL, Harvey A (1991b) Effects of morphine and naloxone upon the reactions of rats to a heat stressor. Q J Exp Psychol 43B:323–346
Zambotti F, Zonta N, Tammiso R, Conci F, Hafner B, Zecca L, Ferrario P, Mantegazza P (1991) Effects of diazepam on nociception in rats. Naunyn-Schmiedeberg's Arch Pharmacol 344:84–89
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Harris, J.A., McGregor, I.S. & Westbrook, R.F. Low and high doses of midazolam differentially affect hypoalgesia in rats conditioned to a heat stressor. Psychopharmacology 111, 62–68 (1993). https://doi.org/10.1007/BF02257408
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DOI: https://doi.org/10.1007/BF02257408