Abstract
Studies were undertaken to determine the effects of acute alterations in plasma glucose levels on the tail skin temperature (TST) response of morphine-dependent rats to naloxone-precipitated withdrawal. In morphine-dependent rats, treatment with dextrose at doses of 0.5 or 2.5 g/kg did not alter the normal 6.0±0.3° C TST response to naloxone. However, treatment with 5, 10 or 20 g dextrose/kg, which increased plasma glucose to 250 mg/dl or greater, blocked the TST response during morphine withdrawal. In contrast, an IV injection of 2.5 IU insulin (Na-porcine)/kg, which reduced plasma glucose for 2 h, caused a delayed TST response of 4.7±0.4° C in control rats and exaggerated the TST response normally observed in morphine-dependent rats treated with naloxone. Collectively, these data indicate that acute hyperglycemia can attenuate and hypoglycemia can enhance the skin vasodilation which accompanies precipitated morphine withdrawal. In view of our observation that naloxone-precipitated morphine withdrawal caused a marked increasee in blood glucose, the sympathetic activation associated with opiate withdrawal may be intended to elevate blood glucose and thereby limit the manifestation of the withdrawal response.
Similar content being viewed by others
References
Akunne HC, Soliman KFA (1988) Hyperglycemia suppression of morphine withdrawal signs in the rat. Psychopharmacology 96:1–6
Berglund LA, Millard WJ, Gabriel SM, Simpkins JW (1990) Opiate-thyroid hormone interactions in the regulation of TSH secretion in the rat. Neuroendocrinology (in press)
Brodie ME, Laverty R, McQueen EG (1983) Rapid changes in catecholamine function in mouse brain during morphine withdrawal. Res Commun Substance Abuse 4:59–67
Crowley JN, Lavery R, Roth RH (1979) Clonidine reversal of increased norepinephrine metabolites during morphine withdrawal. Eur J Pharmacol 57:247–250
Cryer PE, Gerich JE (1983) Relevance of glucose counterregulatory systems to patients with diabetes: critical roles of glucagon and epinephrine. Diabetes Care 6:95–99
Davis WM, Miya TS, Edward LD (1956) The influence of glucose and insulin pretreatment upon morphine analgesia in the rat. J Am Pharm Assoc 45:60–62
Eisenman AJ, Sloan JW, Martin WR, Jasinskin DR, Brooks J (1969) Catecholamine and 17-hydroxycorticosteroid excretion during a cycle of morphine dependence in man. J Psychiatr Res 7:19–28
Gabriel SM, Simpkins JW, Millard WJ (1985) Changes in pituitary hormone secretion and hypothalamic catecholamine metabolism during morphine withdrawal in the female rat. Brain Res 346:15–21
Gold MS, Redmond DE Jr, Kieber HD (1978) Clonidine blocks acute opiate-withdrawal symptoms. Lancet II:599–602
Holzbauer M, Vogt M (1954) The concentration of adrenaline in the peripheral blood during insulin hypoglycemia. Br J Pharmacol 9:249–252
Ichikawa Y, Nishikai M, Kawagie M, Yoshida K, Homma M (1972) Plasma corticotropin, cortisol and growth hormone responses to hypoglycemia in the morning and evening. J Clin Endocrinol Metab 34:895–898
Katovich MJ, O'Meara J (1987) Effects of chronic estrogen on the skin temperature response to naloxone in morphine-dependent rats. Can J Physiol Pharmacol 65:563–567
Katovich MJ, Simpkins JW, Berglund LA, O'Meara J (1986) Regional skin temperature changes in a rat model for the menopausal hot flush. Maturitas 8:67–76
Khalil Z, Marley PD, Livett BG (1986) Elevation in plasma catecholamines in response to insulin stress is under both neuronal and nonneuronal control. Endocrinology 119:159–167
Martin WR, Jasinski DR (1969) Physiological parameters of morphine dependence in man-tolerance, early abstinence, protracted abstinence. J Psychiatr Res 7:9–17
Martin WR, Eades CG, Thompson WO, Thompson JA, Flanary G (1974) Morphine physical dependence in the dog. J Pharmacol Exp Ther 189:759–771
Morley GK, Mooradian AD, Levine AS, Morley JE (1984) Mechanism of pain in diabetic peripheral neuropathy. Effect of glucose on pain perception in humans. Am J Med 77:79–82
Raz I, Hasdai D, Seltzer Z, Melmed RN (1988) Effect of hyperglycemia on pain perception and on efficacy of morphine analgesia in rats. Diabetes 37:1253–1259
Santiago JV, White NH, Skor DA, Levandoski LA, Bier DM, Cryer PE (1984) Defective glucose counterregulation, limits intensive therapy of diabetes mellitus. Am J Physiol 247:E215-E220
Shook E, Dewey W (1986) Morphine dependence and diabetes I. The development of morphine dependence in streptozotocindiabetic rats and spontaneous diabetic C57BL/KSJ mice. J Pharmacol Exp Ther 237:841–847
Shook JE, Kachur J, Brase DA, Dewey WL (1986) Morphine dependence and diabetes II. Alterations of normorphine potency in the guinea pig ileum and mouse vas deferens and of ileal morphine dependence by changes in glucose concentration. J Pharmacol Exp Ther 237:848–852
Simon GS, Dewey WC (1981) Narcotics and diabetes I. The effects of streptozotocin-induced diabetes on the antinociceptive potency of morphine. J Pharmacol Exp Ther 218:318–323
Simon GS, Borzelleca J, Dewey WL (1981) Narcotics and diabetes II. Streptozotocin-induced diabetes selectively alters the potency of certain narcotic analgesics. Mechanism of diabetes-morphine interaction. J Pharmacol Exp Ther 28:324–329
Simpkins JW, Katovich MJ (1989) Relationship between blood glucose and hot flushes in women and an animal model. In: Lomax P, Schonbaum E (eds) Thermoregulation: research and clinical applications. Karger, Basel, pp 95–100
Simpkins JW, Katovich MJ, Song I-C (1983) Similarities between morphine withdrawal in the rat and the menopausal hot flush. Life Sci 32:1957–1966
Smythe GA, Grunstein HS, Bradshaw JE, Nicholson MV, Compton PJ (1984) Relation between brain noradrenergic activity and blood glucose. Nature 308:65–67
Tepperman J (1981) Metabolic and endocrine physiology, 4th edn. Year Book Medical, Chicago, pp 206–221
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Simpkins, J.W., Katovich, M.J. & Millard, W.J. Glucose modulation of skin temperature responses during morphine withdrawal in the rat. Psychopharmacology 102, 213–220 (1990). https://doi.org/10.1007/BF02245924
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02245924