Abstract
The effect of 15 min/day of immobilization (IM) stress on oral self-administration (SA) of morphine (0.5 mg/ml) or fentanyl (25 µg/ml) and withdrawal was examined in rats. In addition, the role of conditioning factors in these effects was assessed. For each drug, four groups of subjects were exposed for 50 days to IM stress prior to the drug SA period [Paired-Stress (P-S) groups], to IM stress prior to the drug SA period on half of the days and after the drug SA period on the rest of the days [Partial Paired-Stress (PP-S) groups], to IM stress several hours after the drug SA period [Unpaired-Stress (UP-S) groups], or to no IM stress [Control (C) groups]. The P-S and PP-S groups increased their drug SA during choice days in which both the opioid solution and water were available, and tended to manifest a more severe withdrawal syndrome after a naloxone challenge compared with the UP-S and C groups. Reinstatement of the opioid SA under conditions of paired-stress or no stress was further examined after 3 weeks without exposure to either stress or drugs. The paired stress animals had higher levels of drug SA and manifested a more severe withdrawal syndrome than those tested without stress. These results indicate that the learned association between exposure to stress and the drug availability may mediate, in part, the stress-induced enhancement of opioid SA and withdrawal effects.
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References
Alexander BK, Hadaway PF (1982) Opiate addiction: the case of an adaptive orientation. Psychol Bull 92:367–381
Appelbaum BD, Holtzman SP (1984) Characterization of stress-induced potentiation of opioid effects in the rats. J Pharmacol Exp Ther 231:555–565
Barrett JE (1987) Nonpharmacological factors determining the behavioral effects of drugs. In: Meltzer HY (ed) Psychopharmacology: the third generation of progress. Raven Press, New York, pp 1493–1501
Buckingham JC, Cooper TA (1984) Differences in hypothalamic-pituitary-adrenocortical activity in the rat after acute and prolonged treatment with morphine. Neuroendocrinology 38:411–417
Cox BM (1988) Peripheral actions mediated by opioid receptors. In: Pasternak GW (ed) The opiate receptors. Humana Press, Clifton, NJ, pp 357–422
Dib B (1985) A study of intrathecal self-injection of morphine by rats, and the difficulties entailed. Pain 23:177–185
Dib B, Duclaux R (1982) Intracerebroventricular self-injection of morphine in response to pain in rats. Pain 13:395–406
Eikelboom R, Stewart J (1982) Conditioning of drug-induced physiological responses. Psychol Rev 89:507–528
Grunberg NE, Baum A (1985) Biological commonalities of stress and substance abuse. In: Shiffman S, Wills TA (eds) Coping and substance abuse. Academic Press, Orlando, pp 25–62
Hinson RE, Poulos CX, Thomas W, Cappell H (1986) Pavlovian conditioning and addictive behavior: relapse to oral self-administration of morphine. Behav Neurosci 100:368–375
Houser VP (1978) The effects of drugs on behavior controlled by aversive stimuli. In: Blackman DE, Sanger DJ (eds) Contemporary research in behavioral pharmacology. Plenum Press, New York, pp 69–157
Jaffe JH (1985) Drug dependence. In: Kaplan HI, Sadock BJ (eds) Comprehensive textbook of psychiatry (4th edn). Williams and Wilkins, Baltimore, pp 987–1033
Kalivas PW, Stewart J (1991) Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity. Brain Res Rev 16:223–244
Kant GJ, Leu JR, Anderson SM, Mougey EH (1987) Effects of chronic stress on plasma corticosterone, ACTH and prolactin. Physiol Behav 40:775–779
Koob GF, Bloom FE (1988) Cellular and molecular mechanisms of drug dependence. Science 242:715–723
Kosten TR, Rounsaville BJ, Kleber HD (1986) A 2.5-year follow-up of depression, life crises, and treatment effects on abstinence among opioid addicts. Arch Gen Psychiatry 43:733–739
Leyton M, Stewart J (1990) Preexposure to foot-shock sensitizes the locomotor response to subsequent systemic morphine and intranucleus accumbens amphetamine. Pharmacol Biochem Behav 37:303–310
Linseman MA (1977) Naloxone-precipitated withdrawal as a function of the morphine-naloxone interval. Psychopharmacology 54:159–164
Mackintosh NJ (1983) Conditioning and associative learning. Oxford University Press, New York
Miczek KA, Thompson ML, Shuster L (1986) Analgesia following defeat in an aggressive encounter: development of tolerance and changes in opioid receptors. Ann NY Acad Sci 467:15–29
Mirin SM, Meyer RE, McNamee BH, McDougale BA (1976) Psychopathology, craving, and mood during heroin acquisition: an experimental study. Int J Addict 11:525–544
O'Brien CP, Ehrman RN, Ternes JW (1986) Classical conditioning in human opioid dependence. In: Goldberg SR, Stolerman IP (eds) Behavioral analysis of drug dependence. Academic Press, New York, pp 329–356
O'Doherty F (1991) Is drug use a response to stress? Drug Alcohol Depend 29:97–106
O'Doherty F, Davies BJ (1987) Life events and addiction: a critical review. Br J Addict 82:127–137
Piazza PV, Deminiere JM, Maccari S, Le Moal M, Mormede P, Simon H (1991) Individual vulnerability to drug-self-administration: action of corticosterone on dopaminergic systems as possible pathophysiological mechanism. In: Willner P, Scheel-Kruger J (eds) The mesolimbic dopaminergic system: from motivation to action. Wiley, New York, pp 473–495
Selye H (1956) The stress of life. McGraw-Hill, New York
Shaham Y, Alvares K, Nespor SM, Grunberg NE (1992) Effect of stress on oral morphine and fentanyl self-administration in rats. Pharmacol Biochem Behav 41:615–619
Shaham Y, Klein LC, Alvares K, Grunberg NE. Effect of stress on oral fentanyl consumption in rats in an operant self-administration paradigm. Pharmacol Biochem Behav (in press)
Shiffman S, Wills TA (1985) Coping and substance abuse. Academic Press, Orlando
Siegel S (1989) Pharmacological conditioning and drug effects. In Goudie AJ, Emmett-Oglesby MW (eds) Psychoactive drugs tolerance and sensitization. Humana Press, Clifton NJ, pp 115–180
Sobrero PA, Bouton ME (1989) Effects of stimuli present during oral morphine administration on withdrawal and subsequent consumption. Psychobiology 17:179–190
Stewart J, Vezina P (1988) Conditioning and behavioral sensitization. In: Kalivas PW, Barnes CD (eds) Sensitization in the nervous system. Telford Press, Caldwell NJ, pp 207–224
Stolerman IP, Kumar R (1970) Preferences for morphine in rats: validation of an experimental model of dependence. Psychopharmacologia 17:137–150
Whitehead CC (1974) Methadone pseudowithdrawal syndrome: paradigm for a psychopharmacological model of opiate addiction. Psychosom Med 36:189–198
Wikler A, Pescor FT (1967) Classical conditioning of a morphine abstinence phenomenon, reinforcement of opioid-drinking behavior and “relapse” in morphine-addicted rats. Psychopharmacologia 20:255–284
Williams JL, Drugan RC, Maier SF (1984) Exposure to uncontrollable stress alters withdrawal from morphine. Behav Neurosci 98:836–846
Wise RA, Bozarth MA (1987) A psychomotor stimulant theory of addiction. Psychol Rev 94:469–492
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Shaham, Y. Immobilization stress-induced oral opioid self-administration and withdrawal in rats: role of conditioning factors and the effect of stress on “relapse” to opioid drugs. Psychopharmacology 111, 477–485 (1993). https://doi.org/10.1007/BF02253539
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DOI: https://doi.org/10.1007/BF02253539