Abstract
On the basis that the medial forebrain bundle system of the anterior brainstem is a major component of the system whose activity is positive affect, it is submitted that any drug that would increase activity in that system has a high risk of becoming the focus of an addiction. When an increase in activity of that system is a contingency of an act (such as imbibing, inhaling, snorting, or injecting), then that act will occur more and more frequently (i.e., positive reinforcement occurs) and this is a basis for an addiction. The potential for a drug to increase activity in the system is often manifested by measuring the lever pressing of rats for a fixed intensity of electrical stimulation of the system. Drugs, therefore, can be screened for their addiction likelihood by observing their effects on pressing for brain stimulation.
The term “abuse liability” is extraordinarily confusing, particularly in the context of this chapter. Discussing all of the problems with the term is beyond the scope of this chapter. It will be sufficient to say here, first, we are concerned with addiction liability. Second, the word liability has two meanings: likelihood and debt. In this context, and perhaps the entire book, it seems that we are attempting to assess addiction likelihood rather than addiction debt or abuse (albeit a likely consequence of addiction). Consequently, my topic is the use of procedures involving ICS in establishing likelihood of addiction. In accordance with modern theory of addiction, particularly opioid addiction (Smith & Lane, 1983), an addiction likelihood, in turn, is strongly related to the potential for a drug to be positively reinforcing.
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References
Adams, W. J., Lorens, S. A., & Mitchell, C. L. (1972). Morphine enhances lateral hypothalamic self-stimulation in the rat. Proceedings of the Society of Experimental Biology and Medicine, 140, 770–771.
Amir, S., Solomon, R., & Amit, Z. (1979). The effect of acute and chronic naloxone administration on motor activation in the rat. Neuropharmacology, 18, 171–173.
Beaman, C., Hunter, G. A., & Reid, L. D. (1984). Diprenorphine, an antagonist of opioid-analgesia elicits a positive affective state in rats. Bulletin of the Psychonomic Society, 22, 354–355.
Becker, B. M., & Reid, L. D. (1977). Changes in pressing for intracranial stimulation (ICS) after prolonged ICS. Physiological Psychology, 5, 58–62.
Belluzzi, J. D., & Stein, L. (1977). Enkephalin may mediate euphoria and drive-reduction reward. Nature, 266, 556–558.
Bermudez-Rattoni, F., Cruz-Morales, S., & Reid, L. D. (1983). Addictive agents and intracranial stimulation (ICS): Novel antagonist and agonists of morphine and pressing for ICS. Pharmacology Biochemistry & Behavior, 18, 777–784.
Bogacz, J., Laurent, J., & Olds, J. (1965). Dissociation of self-stimulation and epileptiform activity. Electroencephalography & Clinical Neurophysiology, 19, 75–87.
Bower, G. H., & Miller, N. E. (1958). Rewarding and punishing effects from stimulating the same place in the rat’s brain. Journal of Comparative and Physiological Psychology, 51, 669–674.
Bozarth, M. A. (1978). Intracranial self-stimulation as an index of opioid addiction liability: An evaluation. Unpublished master’s thesis, Rensselaer Polytechnic Institute, Troy, NY.
Bozarth, M. A. (1983). Opiate reward mechanisms mapped by intracranial self-administration. In J. E. Smith & J. D. Lane (Eds.), Neurobiology of opiate reward mechanisms (pp. 331–359). Amsterdam: Elsevier/North Holland Biomedical Press.
Bozarth, M. A., Gerber, G. J., & Wise, R. A. (1980). Intracranial self-stimulation as a technique to study the rewarding properties of drugs of abuse. Pharmacology Biochemistry & Behavior, 13(Suppl. 1), 245–247.
Bozarth, M. A., & Reid, L. D. (1977). Addictive agents and intracranial stimulation (ICS): Naloxone blocks morphine’s acceleration of pressing for ICS. Bulletin of the Psychonomic Society, 10, 478–480.
Breuker E., Dingledine R., & Iversen, L. L. (1976). Evidence for naloxone and opiates as GABA antagonists. British Journal of Pharmacology, 120, 458.
Brown, D. R., & Holtzman, S. E. (1981). Suppression of drinking by naloxone in the rat: A further characterization. European Journal of Pharmacology, 69, 331–340.
Buckwalter, M. M., Gibson, W. E., Reid, L. D., & Porter, P. B. (1967). Combining positive and negative intracranial reinforcement. Journal of Comparative and Physiological Psychology, 65, 329–331.
Bush, E. D., Bush, M. F., Miller, M. A., & Reid, L. D. (1976). Addictive agents and intracranial stimulation: Daily morphine and lateral hypothalamic self-stimulation. Physiological Psychology, 4, 79–85.
Casper, N. J., & Reid, L. (1975). Complex contingencies. Physiological Psychology, 3, 9–13.
Collaer, M. L., Magnuson, D. J., & Reid, L. D. (1977). Addictive agents and intracranial stimulation (ICS): Pressing for ICS before and after self-administration of sweetened morphine solutions. Physiological Psychology, 5, 425–428.
Collins, R. J., Weeks, J. R., Cooper, M. M., Good, P. I., & Russell, R. R. (1984). Prediction of abuse liability of drugs using IV self-stimulation by rats. Psychopharmacology, 82, 6–13.
Cooper, S. J., & Holtzman, S. E. (1983). Patterns of drinking in the rat following administration of opiate antagonists. Pharmacology Biochemistry & Behavior, 19, 505–511.
Cox, B. M. (1983). Endogenous opioid peptides: A guide to structures and terminology. Life Sciences, 31, 1645–1658.
Crow, T. J. (1970). Enhancement by cocaine of intracranial self-stimulation in the rat. Life Science, 9, 375–381.
Cruz-Morales, S., & Reid, L. D. (1980). Addictive agents and intracranial stimulation (ICS): Morphine, naloxone, and pressing for amygdaloid ICS. Bulletin of the Psychonomic Society, 16, 199–200.
Deneau, G. A., Yanagita, T., & Seevers, M. H. (1969). Self-administration of psychoactive substances by the monkey: A measure of psychological dependence. Psychopharmaco 1 ogia, 16, 30–48.
Deutsch, J. A., & Howarth, C. I. (1963). Some tests of a theory of intracranial self-stimulation. Psychological Review, 70, 446–460.
Esposito, R., & Kornetsky, C. (1977). Morphine lowering of self-stimulation thresholds: Lack of tolerance with long-term administration. Science, 195, 189–191.
Esposito, R., & Kornetsky, C. (1978). Opioids and rewarding brain stimulation. Neuroscience, & Biobehavioral Reviews, 2, 115–122.
Farber, P. D., & Reid, L. D. (1976). Addictive agents and intracranial stimulation (ICS): Daily morphine and pressing for combinations of positive and negative ICS. Physiological Psychology, 4, 262–268.
Franklin, K. B. J., & Robertson, A. (1982). Effects and interactions of naloxone and amphetamine on self-stimulation of the prefrontal cortex and dorsal tegmentum. Pharmacology Biochemistry & Behavior, 16, 433–436.
Gerber, G. J., Bozarth, M. A., & Wise, R. A. (1981). Small-dose intravenous heroin facilitates hypothalamic self-stimulation without response suppression in rats. Life Science, 28, 557–562.
Gibson, W. E., Reid, L. D., Sakai, M., & Porter, P. B. (1965). Intracranial reinforcement compared with sugar-water reinforcement. Science, 148, 1357–1358.
Glick, S. D., Weaver, L. M., & Meibach, R. C. (1982). Asymmetrical effects of morphine and naloxone on reward mechanisms. Psychopharmacology, 78, 219–224.
Goldstein, A. (1978). Opiate receptors and opioid peptides: A ten year overview. In M. A. Lipton, A. DiMascio, K. F. Killam (Eds.), Psychopharmacology: A generation of progress (pp. 1157–1563). New York: Raven Press.
Heath, R. G. (1964). Pleasure response of human beings to direct stimulation of the brain: Physiologic and psychodynamic consideration. In R. G. Heath (Ed.), The role of pleasure in behavior (pp. 219–243). New York: Hoeber.
Hipps, P. P., Eveland, M. R., Meyer, E. R., Sherman, W. R., & Cicero, T. J. (1976). Moss fragmentography of morphine: Relationship between brain levels’ and analgesic activity. Journal of Pharmacology and Experimental Therapeutics, 196, 642–648.
Holtzman, S. G. (1976). Comparison of the effect of morphine, pentazocine, cyclazocine and amphetamine on intra-cranial self-stimulation in the rat. Psychopharmacologia, 46, 223–227.
Hunsicker, J. P., & Reid, L. D. (1974). The “priming effect” in conventionally reinforced rats. Journal of Comparative and Physiological Psychology, 87, 618–621.
Hunter, G. A., Jr., & Reid, L. D. (1983). Assaying addiction liability of opioids. Life Sciences, 33(Suppl. 1), 393–396.
Iversen, S. D. (1983). Brain endorphins and reward function: Some thoughts and speculation. In J. E. Smith & J. D. Lane (Eds.), Neurobiology of opiate reward mechanisms (pp. 439–468). Amsterdam: Elsevier/North Holland Biomedical Press.
Jacobowitz, D. M., & Palkovits, M. (1974). Topographic atlas of catecholamine acetylcholinesterase-containing neurons in the rat brain. I. Forebrain (telencephalon, diencephalon). Journal of Comparative Neurology, 157, 13–28.
Kamei, G., Yoshinobu, M., & Schimizu, M. (1974). Effects of psychotropic drugs on hypothalamic self-stimulation behavior in rats. Japanese Journal of Pharmacology, 24, 613–619.
Katz, R. J. (1980). The temporal structure of motivation. Behavioral and Neural Biology, 30, 148–159.
Katz, R. J. (1981). Identification of a novel class of central reward sites showing a delayed and cumulative response to opiate blockade. Pharmacology Biochemistry & Behavior, 15, 131–134.
Kayan, S., Woods, L. A., & Mitchell, C. L. (1971) Morphine-induced hyperalgesia in rats tested on the hot plate. Journal of Pharmacology and Experimental Therapeutics, 177, 509–513.
Keesey, (1964). Duration of stimulation and reward properties of hypothalamic stimulation. Journal of Comparative and Physiological Psychology, 58, 201–207.
Kimble, G. A. (1961). Hilgard and Marquis’ conditioning and learning. New York: Appleton-Century-Crofts.
Koob, G. F., Spector, N. H., & Meyerhoff, J. L. (1975). Effects of heroin on lever pressing for intracranial self-stimulation, food, and water in the rat. Psychopharmaco1ogia, 42, 231–234.
Liebman, J. M. (1983). Discriminating between reward and performances: A critical review of intracranial self-stimulation methodology. Neuroscience & Behavioral Reviews, 7, 45–72.
Lorens, S. A., & Mitchell, C. L. (1973). Influence of morphine on lateral hypothalamic self-stimulation in the rat. Psychopharmacologia, 32, 271–277.
Lorens, S. A., & Sainati, S. M. (1978). Naloxone blocks the excitatory effect of ethanol and chlordiazepoxide on lateral hypothalamic self-stimulation behavior. Life Sciences, 23, 1359–1364.
Marcus, R., & Kornetsky, C. (1974). Negative and positive intracranial reinforcement thresholds: Effects of morphine. Psychopharmacologia, 38, 1–13.
Mclntire, R. W., & Wright, J. E. (1965). Parameters related to response rate for septal and medial forebrain bundle stimulation. Journal of Comparative and Physiological Psychology, 59, 131–134.
Miller, D. E., Reid, L. D., & Porter, P. B. (1967). Delayed punishment of positively reinforced bar presses. Psychological Reports, 22, 1073–1077.
Mucha, R. F., & Iversen, S. D. (1985). Reinforcing properties of morphine and naloxone revealed by conditioned place preference: A procedural examination. Psychopharmacology, 82, 241–247.
Nelsen, J. M., & Kornetsky, C (1972). Morphine induced EEG changes in central motivational systems: Evidence for single dose tolerance. Fifth International Congress of Pharmacology, 166.
Olds, J. (1962). Hypothalamic substrates of reward. Physiological Reviews, 42, 554–604.
Olds, J., & Milner, P. (1954). Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain. Journal of Comparative and Physiological Psychology, 47, 419–427
Olds, J., & Travis, R. P. (1960). Effects of chlorpromazine, meprobamate, pentobarbital and morphine on self-stimulation. Journal of Pharmacology and Experimental Therapeutics, 128, 397–404.
Olds, M. E. (1966). Facilitory action of diazepam and chlordiazepoxide on hypothalamic reward behavior. Journal of Comparative Physiology and Psychology, 62, 136–140.
Olds, M. E. (1970). Comparative effects of amphetamine, scopolamine, chlordiazepoxide and diphenylhydantoin on operant and extinction behaviour with brain stimulation and food reward. Neuropharmaco1ogy, 9, 519–532.
Pearl, J., Aceto, M. D., & Harris, L. D. (1968). Prevention of writhing and other effects of narcotics and narcotic antagonists in mice. Journal of Pharmacology and Experimental Therapeutics, 160, 217–230.
Perry, W., Esposito, R. U., & Kornetsky, C. (1981). Effects of chronic naloxone treatment on brain-stimulation reward. Pharmacology Biochemistry & Behavior, 14, 247–250.
Pert, A. (1975). Effects of opiates on rewarding and aversive brain stimulation in the rat. Problems of Drug Dependence, 963–973.
Pilcher, C. W. T., Jones, S. M., & Browne, J. (1982). Rhythmic nature of naloxone-induced aversions and nociception in rats. Life Sciences, 31, 1249–1252.
Pollerberg, G. E., Costa, T., Sherman, G. T., Herz, A., & Reid, L. D. (1983). Opioid antinociception and positive reinforcement are mediated by different types of opioid receptors. Life Sciences, 33, 1549–1559.
Reid, L. D. (1967). Reinforcement from direct stimulation of the brain. Unpublished doctoral dissertation, University of Utah, Salt Lake City.
Reid, L. D., & Bozarth, M. A. (1978). Addictive agents and pressing for intracranial stimulation (ICS): The effects of various opioids on pressing for ICS. Problems of Drug Dependence, 729–741.
Reid, L. D., Gibson, W. E., Gledhill, S. M., & Porter, P. B. (1964). Anticonvulsant drugs and self-stimulation behavior. Journal of Comparative and Physiological Psychology, 58, 353–356.
Reid, L. D., & Porter, P. B. (1965). Reinforcement from direct electrical stimulation of the brain. Rocky Mountain Psychologist, 1, 3–22.
Reid, L. D., & Siviy, S. M. (1982). Administration of antagonists of morphine and endorphin reveal endorphinergic involvement in reinforcement processes. In J. E. Smith & J. D. Lane (Eds.), Neurobiology of opiate reward mechanisms (pp. 257–279). Amsterdam: Elsevier/North Holland Biomedical Press.
Riley, A. L., & Baril, L. L. (1 976). Conditioned taste aversion: A bibliography. Animal Learning & Behavior, 4(Suppl.), 15–35.
Rossi, N. A., & Reid, L. D. (1976). Affective states associated with morphine injections. Physiological Psychology, 4, 269–274.
Sakai, M., Reid, L. D., & Porter, P. B. (1965). Why is reinforcing brain stimulation turned off? In Proceedings of the 73rd Annual Convention of the American Psychological Society (pp. 155–156).
Sandberg, D. E., & Segal, M. (1978). Pharmacological analysis of analgesia and self-stimulation elicited by electrical stimulation of catecholamine nuclei in the rat brain. Brain Research, 152, 529–542.
Schnitzer, S. B., Reid, L. D., & Porter, P. B. (1965). Electrical intracranial stimulation as a primary reinforcer for cats. Psychological Reports, 16, 335–338.
Schuster, C. R., & Thompson, T. (1969). Self-administration of and behavioral dependence on drugs. Annual Review of Pharmacology, 9, 483–502.
Simon, E. J. (1982). History. In J. B. Malick & R. M. S. Bell (Eds.), Endorphins: Chemistry, physiology, pharmacology, and clinical relevance (pp. 1–8). New York: Marcel Decke
Siviy, S. M., Calcagnetti, D. J., & Reid, L. D. (1982). A temporal analysis of naloxone’s suppressant effect on drinking. Pharmacology Biochemistry & Behavior, 16, 173–175.
Smith, J. E., Co, C., & Läne, J. D. (1984). Limbic acetylcholine turnover rates correlated with rat morphine-seeking behaviors. Pharmacology Biochemistry & Behavior, 20, 429–442.
Smith, J. E., & Lane, J. D. (Eds.) (1983). Neurobiology of opiate reward mechanisms. Amsterdam: Else vi er /North Holland Biomedical Press.
Snyder, S. H. (1980). Brain peptides as neurotransmitters. Science, 209, 976–983.
Solomon, R. L., & Corbit, J. D. (1974). An opponent process theory of motivation: Temporal dynamics of affect. Psychological Review, 81, 119–145.
Stapleton, J. H. (1979). Naloxone suppression of intracranial self-stimulation: Evidence for the involvement of endogenous opioids in the modulation of intracranial reward. Unpublished master’s thesis, Rensselaer Polytechnic Institute, Troy, NY.
Stapleton, J. M., Merriman, V. J., Coogle, C. L., Gelbard, S. D., & Reid, L. D. (1979). Naloxone reduces pressing for intracranial stimulation of sites in the periaqueductal gray area, accumbens nucleus, substantia nigra, and lateral hypothalamus. Physiological Psychology, 7, 427–436.
Stein, L. (1962). Effects and interactions of imipramine, chlorpromazine, reserpine, and amphetamine on self-stimulation: Possible neurophysiological basis of depression. In J. Wortis (Ed.), Recent advances in biological psychiatry (pp. 288–308). New York: Plenum Press.
Stein, L. (1978). Reward transmitters: Catecholamines and opioid peptides. In M. A. Lipton, A. DiMa&cio, & K. F. Killam (Eds.), Psychopharmacology: A generation of progress (pp. 569–581). New York: Raven Press.
Stein, L., & Ray, O. S. (1960). Brain stimulation reward “thresholds” seif-determined in rat. Psychopharmacologia, 1, 251–256.
Thompson, T., & Schuster, C. R., (1964). Morphine self-administration, food reinforcement and avoidance behavior in rhesus monkeys. Psychopharmacologia, 5, 57–94.
Valenstein, E. S. (1964). Problems of measurement and interpretation with reinforcing brain stimulation. Psychological Review, 71, 415–437.
Valenstein, E. S., & Beer, B. (1961). Unipolar and bipolar electrodes in self-stimulation experiments. American Journal of Physiology, 201, 1181–1186.
van der Kooy, D., LePiane, F. E., & Phillips, A. E. (1977). Apparent independence of opiate reinforcement and electrical self-stimulation systems in rat brain. Life Sciences, 29, 981–986.
Ward, S. J., Pierson, A. K., & Michne, W. F. (1983). Multiple opioid receptor profile in vitro and activity in vivo of the potent opioid antagonist Win 44,441–3. Life Sciences, 33(Suppl. 1), 303–306.
Wasden, R. E., Reid, L. D., & Porter, P. B. (1965). Overnight performance decrements with intracranial reinforcement. Psychological Reports, 16, 653–658.
Wauquier, A., Gilbert, H., Clincke, C., & Franson, J. F. (1983). Parameter selection in a rate free test of brain self-stimulation: Towards an alternative interpretation of drug effects. Behavioural Brain Research, 7, 155–1 64.
Weber, E., Evans, C. J., & Barchas, J. D. (1983). Multiple endogenous ligands for opioid receptors. Trends in Neuroseience, 6, 333–336.
Weeks, J. R. (1962). Experimental morphine addiction: Method for automatic intravenous injections in unrestrained rats. Science, 138, 143–144.
Weibel, S. L., & Wolf, H. H. (1979). Opiate modification of intracranial self-stimulation in the rat. Pharmacology Biochemistry & Behavior, 10, 71–78.
Wise, R. A. (1980). Action of drugs of abuse on brain reward systems. Pharmacology Biochemistry & Behavior, 13(Suppl. 1), 213–223.
Wise, R. A. (1982a). Neuroleptics and operant behavior: The anhedonia hypothesis. The Behavioral and Brain Sciences, 5, 39–53.
Wise, R. A. (1982b). Hypotheses of neuroleptic action: Levels of progress. The Behavioral and Brain Sciences, 5, 78–87.
Wise, R. A. (1983). Brain neuronal systems mediating reward processes. In J. E. Smith & J. D. Lane (Eds.), Neurobiology of opiate reward mechanisms (pp. 405–437). Amsterdam: Elsevier/North Holland Biomedical Press.
Woolverton, W. L., & Schuster, C. R. (1983). Behavioral and pharmacological aspects of opioid dependence: Mixed agonist-antagonists. Pharmacological Reviews, 35, 33–52.
Yardin, E., Guarini, V., & Gallistel, C. (1983). Unilaterally activated systems in rats self-stimulating at sites in the medial forebrain bundle, medial prefrontal cortex, or locus coeruleus. Brain Research, 266, 39–50.
Young, P. T. (1967). Affective arousal: Some implications. American Psychologist, 22, 32–40.
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Reid, L.D. (1987). Tests Involving Pressing for Intracranial Stimulation as an Early Procedure for Screening Likelihood of Addiction of Opioids and Other Drugs. In: Bozarth, M.A. (eds) Methods of Assessing the Reinforcing Properties of Abused Drugs. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-4812-5_19
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