Abstract
Studies examining differential sensitivity to psychoactive drugs in mice suggest that genotype may play a critical role. Furthermore, an involvement of genotype in mediating individual differences in sensitivity to the rewarding effects of several drugs of abuse has also been postulated. The aim of this study was to examine the conditioned rewarding and dopamine-releasing effects of morphine in two outbred rat strains commonly used in addiction research. Additionally, the behavioural and neuroendocrine responses of these strains to the stress of novelty were also examined. Basal locomotor activity was higher in Wistar rats than Sprague-Dawley following exposure to a novel environment. In contrast, elevations in plasma corticosteroid levels following novelty exposure did not differ between the two strains. In a counterbalanced place preference conditioning procedure, increasing doses of morphine (1.0–10.0 mg/kg SC) produced significant conditioned place preferences (CPP) in both Wistar and Sprague-Dawley strains. However, Wistar rats required a significantly larger dose of morphine (5.0 mg/kg) to produce a significant CPP than the Sprague-Dawley rats. In the latter strain, CPP occurred with doses of 3.0 mg/kg and greater. In parallel microdialysis experiments, both strains showed significant dose-related increases in dopamine release in the nucleus accumbens following acute morphine challenge (1.0–10.0 mg/kg SC). Again in Wistar rats, a larger dose of morphine was necessary to produce a significant increase in comparison to Sprague-Dawley rats. These results show that genetically distinct rat strains can show differential sensitivity to opioids, more specifically to drug-seeking responses.
Similar content being viewed by others
References
Ambrosio E, Goldberg SR, Elmer GI (1993) Acquisition and extinction of opioid — reinforced behaviour as a function of genotype: relationships to locomotor activity, stress and acute opioid sensitivity. NIDA Monograph, US Government Printing Office, Washington DC (in press)
Belknap JK (1990) Physical dependence induced by the voluntary consumption of morphine in inbred mice. Pharmacol Biochem Behav 35:311–315
Belknap JK, Crabbe JC (1992) Chromosome mapping of gene loci affecting morphine and amphetamine responses in BXD recombinant inbred mice. In: Kalivas P, Samson H (eds) The neurobiology of alcohol and drug addiction. New York Academy of Sciences, New York
Belknap JK, Noordewier B, Lame M (1989) Genetic dissociation of multiple morphine effects among C57BL/6J, DBA/2J and C3H/HeJ inbred mouse strains. Physiol Behav 46:69–74
Belknap JK, Crabbe JC, Young ER (1993) Voluntary consumption of ethanol in 15 inbred mouse strains. Psychopharmacology 112:503–510
Carboni E, Imperato A, Perrezzani L, Di Chiara G (1989) Amphetamine, cocaine, phencyclidine and nomifensine increase extracellular dopamine concentrations preferentially in the nucleus accumbens of freely moving rats. J Neurosci 28:653–661
Carr GD, Phillips AG, Fibiger HC (1988) Independence of amphetamine reward from locomotor stimulation demonstrated by conditioned place preference. Psychopharmacology 94:221–226
Carr GD, Fibiger HC, Phillips AG (1989) Conditioned place preference as a measure of drug reward. In: Liebman JM, Cooper SJ (eds) The neuropharmacological basis of reward. Clarendon Press, Oxford, pp 264–319
Crabbe JC, McSwigan JD, Belknap JK (1985) The role of genetics in substance abuse. In: Galizio M, Maisto SA (eds) Determinants of substance abuse: biological psychological, and environmental factors. Plenum Press, New York, pp 13–64
Cunningham CL, Niehus DR, Malott DH, Prather LK (1992) Genetic differences in the rewarding and activating effects of morphine and ethanol. Psychopharmacology 107:385–393
Di Chiara G, Imperato A (1988a) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci USA 85:5274–5278
Di Chiara G, Imperato A (1988b) Opposite effects of Mu and Kappa opiate agonists on dopamine release in the nucleus accumbens and in the dorsal caudate of freely moving rats. J Pharmacol Exp Ther 244:1067–1080
Elmer GI, Meisch RA, Goldberg SR, George FR (1990) Ethanol self-administration in long sleep and short sleep mice indicates reinforcement is not inversely related to neurosensitivity. J Pharmacol Exp Ther 254:1054–1062
George FR, Goldberg SR (1989) Genetic approaches to the analysis of the addiction process. Trends Pharmacol Sci 10:78–83
George FR, Elmer GI, Meisch RA, Goldberg SR (1991) Orally delivered cocaine functions as a positive reinforcer in C57BL/6J mice. Pharmacol Biochem Behav 38:897–903
Gilbert DB, Cooper SJ (1983)β-phenylethylamine,d-amphetamine, and 1-amphetamine-induced place preference conditioning in rats. Eur J Pharmacol 95:311–314
Guitart X, Beitner-Johnson D, Marby DW, Kosten T, Nestler EJ (1992) Fischer and Lewis rat strains differ in basal levels of neurofilament proteins and their regulation by chronic morphine in the mesolimbic dopamine system. Synapse 12:242–253
Guitart X, Kogan JH, Berhow M, Terwilliger RZ, Aghajanian GK, Nestler EJ (1993) Lewis and Fischer rat strains display differences in biochemical, electrophysiological and behavioural parameters: studies in the nucleus accumbens and locus coeruleus of drug naive and morphine-treated animals. Brain Res 611:7–17
Harfstrand A, Fuxe K, Cintra A, Agnati LF, Zini I, Wikstrom A, Okret S, Yu Z, Goldstein M, Steinbusch H, Verhofstrand A, Gustafsson J (1986) Glucocorticoid receptor immunoreactivity in monoaminergic neurons of rat brain. Proc Natl Acad Sci USA 83:9779–9783
Hooks MS, Jones GH, Smith AD, Neill DB, Justice JB (1991) Individual differences in locomotor activity and sensitization. Pharmacol Biochem Behav 38:467–470
Hooks MS, Colvin AC, Juncos JL, Justice JB, Jr (1992) Individual differences in basal and cocaine-stimulated extracellular dopamine in the nucleus accumbens using quantitative microdialysis. Brain Res 587:306–312
Koob GF, Goeders NE (1989) Neuroanatomical substrates of drug self-administration. In: Liebman JM, Cooper SJ (eds) The neuropharmacological basis of reward. Oxford Science Publications, Oxford, pp 214–263
Mucha RF, Iversen SD (1984) Reinforcing properties of morphine and naloxone revealed by conditioned place preferences: a procedural examination. Psychopharmacology 82:241–247
Oliveiro A, Castellano C, Elefttherou BE (1975) Morphine sensitivity and tolerance: A genetic investigation in the mouse. Psychopharmacologia 42:219–224
Piazza PV, Deminière J-M, LeMoal M, Simon H (1989) Factors that predict individual vulnerability to amphetamine self-administration. Science 245:1511–1513
Piazza PV, Maccari S, Deminière J-M, LeMoal M, Mormede P, Simon H (1991) Corticosterone levels determine individual vulnerability to amphetamine self-administration. Proc Natl Acad Sci 88:2088–2092
Racagni G. Bruno F, Iuliano E, Paoletti R (1979) Differential sensitivity to morphine-induced analgesia and motor activity in two inbred strains of mice: Behavioural and biochemical correlations. J Pharmacol Exp Theor 209:111–116
Rouge-Pont F, Piazza PV, Kharouby M, LeMoal M, Simon H (1993) Higher and longer stress-induced increase in dopamine concentrations in the nucleus accumbens of animals predisposed to amphetamine self-administration. A microdialysis study. Brain Res 602:169–174
Shippenberg TS, Herz A (1987) Place preference conditioning reveals the involvement of D1-dopamine receptors in the motivational properties ofμ- andκ-opioid agonists. Brain Res 436:169–172
Shippenberg TS, Bals-Kubik R, Herz A (1987) Motivational properties of opioids: evidence that an activation of d-receptors mediates reinforcement processes. Brain Res 436:234–239
Shippenberg TS, Emmett-Oglesby MW, Herz A (1989) Morphine-induced place conditioning is not confounded by drug-induced alterations in locomotor activity. Pharmacol Biochem Behav 32:129–132
Shoaib M, Spanagel R, Stoehr T, Shippenberg TS (1993) Strain differences in the rewarding and dopamine-releasing effects of morphine in rats. NIDA Monograph, US Government Printing Office, Washington DC (in press)
Spanagel R, Shippenberg TS (1993) Modulation of morphine-induced sensitisation by endogenous kappa opioid systems in the rat. Neurosci Lett 153:232–236
Spanagel R, Herz A, Bals-Kubik R, Shippenberg TS (1991)β-endorphin-induced locomotor stimulation and reinforcement are associated with an increase in dopamine release in the nucleus accumbens. Psychopharmacology 104:51–56
Spanagel R, Herz A, Shippenberg TS (1992) Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proc Natl Acad Sci USA 89:2046–2050
Wise RA, Bozarth MA (1987) A psychomotor stimulant theory of addiction. Psychol Rev 94:469–492
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Shoaib, M., Spanagel, R., Stohr, T. et al. Strain differences in the rewarding and dopamine-releasing effects of morphine in rats. Psychopharmacology 117, 240–247 (1995). https://doi.org/10.1007/BF02245193
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02245193