Abstract
The present study examined the effects of naloxone on acquisition and expression of morphine-induced conditioned place preference (CPP). Three groups of rats were given morphine (5 mg/kg, SC), both morphine and naloxone (1 mg/kg, SC), or saline paired with a distinctive environment. On alternating days they were given saline paired with another distinctive environment. After four exposures to each environment, the animals were given a preference test in which they had access to both environments simultaneously while under the influence of either naloxone (1 mg/kg, SC) or saline. Morphine-conditioned animals showed CPP evident as an increased amount of time spent in the drug-associated environment relative to saline controls. Rats given both naloxone and morphine during conditioning, and saline on the test day, did not show CPP. In contrast, morphine-conditioned animals given naloxone on the test day showed stronger CPP than morphine-conditioned animals given saline. These findings indicate that naloxone blocks the acquisition, but enhances the expression of morphine-induced CPP. In a separate experiment, the effects of naloxone on locomotor activity were determined during the CPP test. The results indicated that naloxone decreased locomotor activity. In morphine-conditioned animals only, naloxone also produced an increase in the amount of time per entry in the drug-associated environment. The results suggest that naloxone may enhance morphine-induced CPP by decreasing locomotor activity that may otherwise compete with expression of CPP.
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References
Bardo MT, Miller JS, Neisewander JL (1984) Conditioned place preference with morphine: The effect of extinction training on the reinforcing CR. Pharmacol Biochem Behav 21:545–549
Beach HD (1957) Morphine addiction in rats. Can J Psychol 11:104–112
Blander H, Hunt T, Blair R, Amit Z (1984) Conditioned place preference: An evaluation of morphine's positive reinforcing properties. Psychopharmacology 84:124–127
Bozarth MA (1987) Conditioned place preference: a parametric analysis using systemic heroin injections. In: Bozarth MA (ed) Methods of assessing the reinforcing properties of abused drugs. Springer, Berlin Heidelberg New York, pp 241–273
Drawbaugh R, Lal H (1974) Reversal by narcotic antagonist of a narcotic action elicited by a conditional stimulus. Nature 247:65–67
Ettenberg A, Pettit HO, Bloom FE, Koob GF (1982) Heroin and cocaine self-administration in rats: mediation by separate neural systems. Psychopharmacology 78:204–209
Grabowski J, Cherek DR (1983) Conditioning factors in opiate dependence. In: Smith JE, Lane JD (eds) The neurobiology of opiate reward processes. Elsevier, Amsterdam, pp 175–210
Katz RJ, Gormezano G (1979) A rapid and inexpensive technique for assessing the reinforcing effects of opiate drugs. Pharmacol Biochem Behav 11:231–233
Koob GF, Pettit HO, Ettenberg A, Bloom FE (1984) Effects of opiate antagonists and their quartenary derivatives on heroin self-administration in the rat. J Pharmacol Exp Ther 229:481–486
Kumar R (1972) Morphine dependence in rats: secondary reinforcement from environmental stimuli. Psychopharmacologia 25:332–338
Lal H, Miksic S, Drawbaugh R, Numan R, Smith N (1976a) Alleviation of narcotic withdrawal syndrome by conditioned stimuli. Pavlov J Biol Sci 11:251–262
Lal H, Miksic S, Smith N (1976b) Naloxone antagonism of conditioned hyperthermia: an evidence for release of endogenous opioid. Life Sci 18:971–975
Mucha RF, Iversen SD (1984) Reinforcing properties of morphine and naloxone revealed by conditioned place preferences: a procedural examination. Psychopharmacology 82:241–247
Neisewander JL, Bardo MT (1987) Expression of morphine-conditioned hyperactivity is attenuated by naloxone and pimozide. Psychopharmacology 93:314–319
O'Brien CP, Ternes JW, Grabowski J, Ehrman R (1981) Classically conditioned phenomena in human opiate addiction. In: Thompson T, Johanson C (eds) Behavioral pharmacology of human drug dependence. National Institute on Drug Abuse, DHHS, Washington DC, Publication No. (ADM) 81-1137, pp 107–115
Rossi NA, Reid LD (1976) Affective states associated with morphine injections. Physiol Psychol 4:269–274
Stewart J, de Wit H, Eikelboom R (1984) Role of unconditioned and conditioned drug effects in the self-administration of opiates and stimulants. Psychol Rev 91:251–268
van der Kooy D (1987) Place conditioning: a simple and effective method for assessing the motivational properties of drugs. In: Bozarth MA (ed) Methods of assessing the reinforcing properties of abused drugs. Springer, Berlin Heidelberg New York, pp 229–240
Vezina P, Stewart J (1987a) Conditioned locomotion and place preference elicited by tactile cues paired exclusively with morphine in an open field. Psychopharmacology 91:375–380
Vezina P, Stewart J (1987b) Morphine conditioned place preference and locomotion: the effect of confinement during training. Psychopharmacology 93:257–260
Wei E, Loh HH, Way EL (1973) Quantitative aspects of precipitated abstinence in morphine-dependent rats. J Pharmacol Exp Ther 184:398–403
Wikler A, Pescor FT (1967) Classical conditioning of a morphine abstinence phenomenon, reinforcement of opioid drinking behavior and ‘relapse’ in morphine addicted rats. Psychopharmacologia 10:255–284
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Neisewander, J.L., Pierce, R.C. & Bardo, M.T. Naloxone enhances the expression of morphine-induced conditioned place preference. Psychopharmacology 100, 201–205 (1990). https://doi.org/10.1007/BF02244406
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DOI: https://doi.org/10.1007/BF02244406