Abstract
Rats were trained to bar-press in order to obtain electrical stimulation of the medial forebrain bundle through chronically implanted electrodes. Dose-response and time-effect curves were determined for morphine (1.0–30 mg/kg), levorphanol (0.1 to 3.0 mg/kg), methadone (0.1–3.0 mg/kg), meperidine (1.0–30 mg/kg), oxymorphone (0.03–1.0 mg/kg), and d-amphetamine (0.1–3.0 mg/kg). Dose-response and time-effect curves were also determined for morphine (1.0–30 mg/kg) in rats that had received multiple injections of morphine over a period of 3 days. All of the narcotic analgesics produced dose-related decreases in responding; the durations of these decreases were also dose-related. The relative potencies of the five narcotic analgesics with respect to the rate-decreasing effects for self-stimulation responding were: oxymorphone > levorphanol > methadone > morphine > meperidine. In morphine-tolerant rats the rate-decreasing effects of morphine on responding for self-stimulation were attenuated. These findings suggest that narcotic analgesics from diverse chemical families have a similar, predominantly depressant, effect on self-stimulation behavior and that the relative potencies of a series of narcotics for this effect are similar to those demonstrated for other properties of these drugs.
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References
Adams, W. J., Lorens, S. A., Mitchell, C. L.: Morphine enhances lateral hypothalamic self-stimulation. Proc. Soc. Exp. Biol. Med. 140, 770–771 (1972)
Bush, H. D., Bush, M. F., Miller, M. A., Reid, L. D.: Addictive agents and intracranial stimulation: daily morphine and lateral hypothalamic self-stimulation. Physiol. Psychol. 4, 79–85 (1976)
Domino, E. F., Wilson, A.: Effects of narcotic analgesic agonists and antagonists on rat brain acetylcholine. J. Pharmacol. Exp. Ther. 184, 18–32 (1973)
Edwards, A. L.: Experimental design in psychological research, pp. 130–154. New York: Holt, Rinehart and Winston 1968
German, D. C., Bowden, D. M.: Catecholamine systems as the neural substrate for intracranial self-stimulation: a hypothesis. Brain Res. 73, 381–419 (1974)
Glick, S. D., Rapaport, G.: Tolerance to the facilitatory effect of morphine on self-stimulation of the medial forebrain bundle of rats. Res. Commun. Chem. Pathol. Pharmacol. 9, 647–652 (1974)
Holtzman, S. G.: Tolerance to the stimulant effects of morphine and pentazocine on avoidance responding in the rat. Psychopharmacologia (Berl.) 39, 23–47 (1974)
Holtzman, S. G.: Comparison of the effects of morphine, pentazocine, cyclazocine and amphetamine on intracranial self-stimulation in the rat. Psychopharmacologia (Berl.) 46, 223–227 (1976)
Holtzman, S. G., Jewett, R. E.: Shock intensity as a determinant of the behavioral effects of morphine in the rat. Life Sci. 11, 1085–1091 (1972)
Jaffe, J. H., Martin, W. R.: Narcotic analgesics and antagonists. In: The pharmacological basis of therapeutics, L. S. Goodman and A. Gilman, eds., pp. 245–283, New York: MacMillan 1975
Lorens, S. A.: Comparison of the effects of morphine on hypothalamic and medial frontal cortex self-stimulation in the rat. Psychopharmacology 48, 217–224 (1976)
Lorens, S. A., Mitchell, C. L.: Influence of morphine on lateral hypothalamic self-stimulation in the rat. Psychopharmacologia (Berl.) 32, 271–277 (1973)
Olds, M. E.: Effectiveness of morphine and ineffectiveness of diazepam and phenobarbital on the motivational properties of hypothalamic self-stimulation behavior. Neuropharmacology 15, 117–131 (1976)
Pellegrino, L. J., Cushman, A. J.: A stereotaxic atlas of the rat brain. New York: Appleton-Century-Crofts 1967
Pert, A., Hulsebus, R.: Effect of morphine on intracranial self-stimulation behavior following brain amine depletion. Life Sci. 17, 19–20 (1975)
Rethy, C. R., Smith, C. B., Villarreal, J. E.: Effects of narcotic analgesics upon the locomotor activity and brain catecholamine content of the mouse. J. Pharmacol. Exp. Ther. 176, 472–479 (1971)
Schaefer, G. J., Holtzman, S. G.: Discriminative effects of morphine in the squirrel monkey. J. Pharmacol. Exp. Ther. 201, 67–75 (1977)
Schuster, C. R., Dockens, W. S., Woods J. H.: Behavioral variables affecting the development of amphetamine tolerance. Psychopharmacologia (Berl.) 9, 170–182 (1966)
Seevers, M. H., Deneau, G. A.: Physiological aspects of tolerance and physical dependence. In: Physiological pharmacology, W. S. Root and F. G. Hofmann, eds., vol. 1, pp. 565–640. New York: Academic Press 1963
Shannon, H. E., Holtzman, S. G.: Evaluation of the discriminative effects of morphine in the rat. J. Pharmacol. Exp. Ther. 198, 54–65 (1976)
Stein, L.: Self-stimulation of the brain and the central stimulant action of amphetamine. Fed. Proc. 23, 836–850 (1964)
Wauquier, A., Niemegeers, C. J. E.: Intracranial self-stimulation in rats as a function of various stimulus parameters. VI. Influence of fentanyl, piritramide, and morphine on medial forebrain bundle stimulation with monopolar electrodes. Psychopharmacologia (Berl.) 46, 179–183 (1976)
Winer, B. J.: Statistical principles in experimental design. New York: McGraw-Hill 1971
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Schaefer, G.J., Holtzman, S.G. Dose- and time-dependent effects of narcotic analgesics on intracranial self-stimulation in the rat. Psychopharmacology 53, 227–234 (1977). https://doi.org/10.1007/BF00492356
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DOI: https://doi.org/10.1007/BF00492356