Abstract
It has been suggested that anxiety may be a critical factor in certain forms of non-opioid environmental analgesia. In the present study, 5-min exposure to the elevated plus-maze test of anxiety (EPM) induced a mild, though enduring, elevation in tail-flick latencies in male mice. Pretreatment with the opiate antagonist naltrexone (0.1–10.0 mg/kg) failed to block EPM-induced antinociception; indeed, the highest dose actuallyenhanced the response. This effect could not be attributed to intrinsic analgetic activity of naltrexone. Rather, analysis of EPM behaviours suggested that it may have been secondary to an anxiogenic effect of the compound. The involvement of non-opioid substrates in this form of pain inhibition was further supported by the failure of chronic morphine treatment (7 days; 7.5 mg/kg) to alter either the antinociceptive or behavioural response to EPM exposure. Irrespective of treatment history, mice showed a retest EPM profile of enhanced anxiety, with tail-flick data suggesting a major contribution of anticipatory factors. Several important methodological variables are discussed and findings are contrasted with parallel studies on non-opioid defeat analgesia.
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References
Amir S (1986) Catalepsy induced by body pinch: relation to stress-induced analgesia. Ann NY Acad Sci 467:226–237
Amit Z, Galina ZH (1986) Stress-induced analgesia: adaptive pain suppression. Physiol Rev 66:1091–1120
Baldwin HA, File SE (1988) Reversal of increased anxiety during benzodiazepine withdrawal: evidence for an anxiogenic endogenous ligand for the benzodiazepine receptor. Brain Res Bull 20:603–606
Bolles RC, Fanselow MS (1980) A perceptual-defensive-recuperative model of fear and pain. Behav Brain Sci 3:291–323
Critchley MAE, Handley SL (1987) Effects in the X-maze anxiety model of agents acting at 5-HT1 and 5-HT2 receptors. Psychopharmacology 93:502–506
Fanselow MS (1986) Conditioned fear-induced opiate analgesia: a competing motivational state theory of stress analgesia. An NY Acad Sci 467:40–54
Handley SL, Mithani S (1984) Effects of alpha-adrenoceptor agonists and antagonists in a maze-exploration model of “fear”-motivated behaviour. Naunyn-Schmiedeberg's Arch Pharmacol 327:1–5
Johnston A, File SE (1988) Profiles of the antipanic compounds, triazolobenzodiazepines and phenelzine, in two animal tests of anxiety. Psychiatry Res 25:81–90
Katz RJ (1988) Endorphins, exploration and activity. In: Rodgers RJ, Cooper SJ (eds) Endorphins, opiates and behavioural processes. Wiley, Chichester, pp 249–268
Kavaliers M, Innes DGL (1988a) Scent-induced non-opioid analgesia in the deer mouse,Peromyscus maniculatus: involvement of benzodiazepine systems. Physiol Behav 42:131–135
Kavaliers M, Innes DGL (1988b) Novelty-induced analgesia in deer mice(Peromyscus maniculatus): sex and population differences. Behav Neural Biol 49:54–60
Kelly DD (ed) (1986) Stress-induced analgesia. NY Academy of Sciences, New York, vol 467
Liebsekind JC, Geisler GJ, Urca G (1976) Evidence pertaining to an endogenous mechanism of pain inhibition in the central nervous system. In: Zotterman Y (ed) Sensory functions of the skin in primates. Pergamon Press, London, pp 561–573
Lister RG (1987) The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology 92:180–185
Miczek KA, Thompson ML, Shuster L (1982) Opiate-like analgesia in defeated mice. Science 215:1520–1522
Montgomery KC (1958) The relation between fear induced by novelty stimulation and exploratory behaviour. J Comp Physiol Psychol 48:254–260
Morato S, Castrechini P (1989) Effects of floor surface and environmental illumination on exploratory activity in the elevated plus-maze. Braz J Med Biol Res 22:707–710
Moser PC (1989) An evaluation of the elevated plus-maze test using the novel anxiolytic buspirone. Psychopharmacology 99:48–53
Mucha RF, Walker MJK (1987) Aversive property of opioid receptor blockade in drug naive mice. Psychopharmacology 93:483–488
Pellow S, File SE (1986) Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat. Pharmacol Biochem Behav 24:525–529
Pellow S, Chopin P, File SE, Briley M (1985) Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 14:149–167
Rago L, Kiivet R-A, Harro J, Pold M (1988) Behavioural differences in an elevated plus-maze: correlation between anxiety and decreased number of GABA and benzodiazepine receptors in mouse cerebral cortex. Naunyn-Schmiedeberg's Arch Pharmacol 337:675–678
Randall JI, Rodgers RJ (1987) Adaptive pain inhibition in murine resident-intruder interactions. Int J Neurosci 41:251–259
Rodgers RJ, Randall JI (1985a) Social conflict analgesia: studies on naloxone antagonism and morphine cross-tolerance in male DBA/2 mice. Pharmacol Biochem Behav 23:883–888
Rodgers RJ, Randall JI (1985b) Strain differences in behaviourally-induced antinociception and morphine analgesia in male mice. Br J Pharmacol 84:105P
Rodgers RJ, Randall JI (1986a) Acute non-opioid analgesia in defeated male mice. Physiol Behav 36:947–950
Rodgers RJ, Randall JI (1986b) Resident's scent: a critical factor in acute analgesic reaction to defeat experience in male mice. Physiol Behav 37:317–322
Rodgers RJ, Randall JI (1987) Benzodiazepine ligands, nociception and “defeat” analgesia in male mice. Psychopharmacology 91:305–315
Rodgers RJ, Randall JI (1988) Environmentally-induced analgesia: situational factors, mechanisms and significance. In: Rodgers RJ, Cooper SJ (eds) Endorphins, opiates and behavioural processes. Wiley, Chichester, pp 107–142
Rodgers RJ Shepherd JK (1988) Effects of endogenous anxiolytic adrenal steroid, α-THDOC, on non-opioid defeat analgesia in male mice: interaction with Ro15-1788. J Psychopharmacol 2:269–278
Rodgers RJ, Shepherd JK (1989a) 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), inhibits non-opioid analgesia in defeated mice: influence of route of injection. Psychopharmacology 97:163–165
Rodgers RJ, Shepherd JK (1989b) Prevention of the analgesic consequences of social defeat in male mice by 5-HT1A anxiolytics, buspirone, gepirone and ipsapirone. Psychopharmacology 99:374–380
Rodgers RJ, Shepherd JK, Randall JI (1990) Highly potent effects of 5-HT3 anxiolytic, GR38032F, on defeat analgesia in mice. Neuropharmacology 29:17–23.
Siegfried B, Netto CA, Izquierdo I (1987) Exposure to novelty induces naltrexone-reversible analgesia in rats. Behav Neurosci 101:436–438
Soderpalm S, Hjorth S, Engel JA (1989) Effects of 5-HT1A receptor agonists andl-5-HTP in Montgomery's conflict test. Pharmacol Biochem Behav 32:259–265.
Tricklebank MD, Curzon G (1984) Stress-induced analgesia. Wiley, Chichester
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Lee, C., Rodgers, R.J. Antinociceptive effects of elevated plus-maze exposure: influence of opiate receptor manipulations. Psychopharmacology 102, 507–513 (1990). https://doi.org/10.1007/BF02247133
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DOI: https://doi.org/10.1007/BF02247133