Drug abuse: Hedonic homeostatic dysregulation

Science

Volumn 278, Issue 5335, 1997, Pages 52-58

  Koob, George F ^a   Le Moal, Michel ^b  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b UNIVERSITÉ DE BORDEAUX   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; BRAIN DYSFUNCTION; DISEASE PREDISPOSITION; DISTRESS SYNDROME; DOPAMINERGIC SYSTEM; DRUG ABUSE; HOMEOSTASIS; HUMAN; LIMBIC SYSTEM; NEUROBIOLOGY; PRIORITY JOURNAL; PSYCHIATRY; REWARD; SOCIAL PSYCHOLOGY;

ADAPTATION, PHYSIOLOGICAL; AMYGDALA; ANIMALS; BEHAVIOR, ADDICTIVE; BRAIN; DOPAMINE; HOMEOSTASIS; HUMANS; NEUROTRANSMITTER AGENTS; RECURRENCE; REINFORCEMENT (PSYCHOLOGY); REWARD; STREET DRUGS; SUBSTANCE WITHDRAWAL SYNDROME; SUBSTANCE-RELATED DISORDERS;

EID: 0030756351     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.278.5335.52     Document Type: Article

References (101)

1. J. H. Jaffe, in Goodman and Gilman's The Pharmacological Basis of Therapeutics, A. G. Gilman, T. W. Rall, A. S. Nies, P. Taylor, Eds. (Pergamon, New York, ed. 8, 1990), pp. 522-573.
2. World Health Organization, International Statistical Classification of Diseases and Related Health Problems (World Health Organization, Geneva, 10th revision, 1990).
3. Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, Washington, DC, ed. 4, 1994).
4. A recent Institute of Medicine report [Institute of Medicine, Pathways of Addiction (National Academy Press, Washington, DC, 1996)] used a three-stage conceptualization of drug-taking behavior that applies to all psychoactive drugs, whether licit or illicit: use, abuse, and dependence. "Use" of drugs is the taking of drugs, in the narrow sense, to distinguish it from a more intensified pattern of use. "Abuse" refers to any harmful use, regardless of whether the behavior constitutes a disorder in the DSM-IV of the American Psychiatric Association. "Dependence" refers to "substance dependence" as defined by DSM-IV or "addiction" as defined by International Classification of Diseases (ICD 10).
5. G. F. Koob and E. J. Nestler, J. Neuropsychiatry Clin. Neurosci. 9, 482 (1997); P. V. Piazza and M. Le Moal, Brain Res. Rev., in press.
6. G. F. Koob and E. J. Nestler, J. Neuropsychiatry Clin. Neurosci. 9, 482 (1997); P. V. Piazza and M. Le Moal, Brain Res. Rev., in press.
7. Underregulation can be defined as a "failure to exert control over one's self." Conflicting or inadequate standards would be a breakdown in the basis for self-regulation. Reduction in monitoring is a failure of a person to evaluate one's self and actions against relevant standards. Inadequate strength is analogous to the common-sense concept of willpower and is a conflict between the power of impulse/tendency to act and the self-regulatory mechanism to interrupt that response and prevent action. Misregulation can be defined as "exerting control in a way that fails to bring about the desired result or leads to some alternative result." Misregulation probably most often involves some kind of deficiency in knowledge, especially self-knowledge. These knowledge deficiencies include false beliefs, distorted beliefs, overgeneralizations, and misdirected control efforts. Lapse-activated causal patterns are the patterns of behavior that translate an initial lapse (break in self-regulation) into a large-scale indulgence or major binge. Many factors contribute to these patterns of behavior, including underregulation, emotional responses, stress, zero-tolerance beliefs, spiralling distress, and others [R. F. Baumeister, T. F. Heatherton, D. M. Tice, Eds., Losing Control: How and Why People Fail at Self-Regulation (Academic Press, San Diego, 1994)].
8. The use of animal models to characterize the neurobiology of specific aspects of human disorders is a reorientation to the "top-down" approach. Here, specific behaviors are explored at the system level, the cellular level, and ultimately the molecular level, with hypothesis testing based on an understanding of the mechanism of the behavioral response [A. Markou et al., Psychopharmacology 112, 163 (1993); G. F. Koob, in Psychopharmacology: The Fourth Generation of Progress, F. E. Bloom and D. J. Kupfer, Eds. (Raven Press, New York, 1995), pp. 759-772; G. F. Koob et al., J. Psychopharmacol., in press].
9. The use of animal models to characterize the neurobiology of specific aspects of human disorders is a reorientation to the "top-down" approach. Here, specific behaviors are explored at the system level, the cellular level, and ultimately the molecular level, with hypothesis testing based on an understanding of the mechanism of the behavioral response [A. Markou et al., Psychopharmacology 112, 163 (1993); G. F. Koob, in Psychopharmacology: The Fourth Generation of Progress, F. E. Bloom and D. J. Kupfer, Eds. (Raven Press, New York, 1995), pp. 759-772; G. F. Koob et al., J. Psychopharmacol., in press].
10. The use of animal models to characterize the neurobiology of specific aspects of human disorders is a reorientation to the "top-down" approach. Here, specific behaviors are explored at the system level, the cellular level, and ultimately the molecular level, with hypothesis testing based on an understanding of the mechanism of the behavioral response [A. Markou et al., Psychopharmacology 112, 163 (1993); G. F. Koob, in Psychopharmacology: The Fourth Generation of Progress, F. E. Bloom and D. J. Kupfer, Eds. (Raven Press, New York, 1995), pp. 759-772; G. F. Koob et al., J. Psychopharmacol., in press].
11. G. F. Koob and F. E. Bloom, Science 242, 715 (1988).
12. R. A. Wise and P.-P. Rompre, Annu. Rev. Physiol. 40, 191 (1989); M. Le Moal and H. Simon, Physiol. Rev. 71, 155 (1991); G. F. Koob, Trends Pharmacol. Sci. 13, 177 (1992); F. E. Pontieri, G. Tanda, F. Orzi, G. Di Chiara, Nature 382, 255 (1996).
13. R. A. Wise and P.-P. Rompre, Annu. Rev. Physiol. 40, 191 (1989); M. Le Moal and H. Simon, Physiol. Rev. 71, 155 (1991); G. F. Koob, Trends Pharmacol. Sci. 13, 177 (1992); F. E. Pontieri, G. Tanda, F. Orzi, G. Di Chiara, Nature 382, 255 (1996).
14. R. A. Wise and P.-P. Rompre, Annu. Rev. Physiol. 40, 191 (1989); M. Le Moal and H. Simon, Physiol. Rev. 71, 155 (1991); G. F. Koob, Trends Pharmacol. Sci. 13, 177 (1992); F. E. Pontieri, G. Tanda, F. Orzi, G. Di Chiara, Nature 382, 255 (1996).
15. R. A. Wise and P.-P. Rompre, Annu. Rev. Physiol. 40, 191 (1989); M. Le Moal and H. Simon, Physiol. Rev. 71, 155 (1991); G. F. Koob, Trends Pharmacol. Sci. 13, 177 (1992); F. E. Pontieri, G. Tanda, F. Orzi, G. Di Chiara, Nature 382, 255 (1996).
16. W. L. Woolverton, Pharmacol. Biochem. Behav. 24, 531 (1986); G. F. Koob, H. T. Le, I. Creese, Neurosci. Lett. 79, 315 (1987); J. Bergman, J. B. Kamien, R. D. Spealman, Behav. Pharmacol. 1, 355 (1990); S. B. Caine and G. F. Koob, Science 260, 1814 (1993).
17. W. L. Woolverton, Pharmacol. Biochem. Behav. 24, 531 (1986); G. F. Koob, H. T. Le, I. Creese, Neurosci. Lett. 79, 315 (1987); J. Bergman, J. B. Kamien, R. D. Spealman, Behav. Pharmacol. 1, 355 (1990); S. B. Caine and G. F. Koob, Science 260, 1814 (1993).
18. W. L. Woolverton, Pharmacol. Biochem. Behav. 24, 531 (1986); G. F. Koob, H. T. Le, I. Creese, Neurosci. Lett. 79, 315 (1987); J. Bergman, J. B. Kamien, R. D. Spealman, Behav. Pharmacol. 1, 355 (1990); S. B. Caine and G. F. Koob, Science 260, 1814 (1993).
19. W. L. Woolverton, Pharmacol. Biochem. Behav. 24, 531 (1986); G. F. Koob, H. T. Le, I. Creese, Neurosci. Lett. 79, 315 (1987); J. Bergman, J. B. Kamien, R. D. Spealman, Behav. Pharmacol. 1, 355 (1990); S. B. Caine and G. F. Koob, Science 260, 1814 (1993).
20. D. W. Self, W. J. Barnhart, D. A. Lehman, E. J. Nestler, Science 271, 1586 (1996).
21. G. Di Chiara and R. A. North, Trends Pharmacol. Sci. 13, 185 (1992); T. S. Shippenberg, A. Herz, R. Spanagel, R. Bals-Kubik, C. Stein, Ann. N. Y. Acad. Sci. 654, 347 (1992).
22. G. Di Chiara and R. A. North, Trends Pharmacol. Sci. 13, 185 (1992); T. S. Shippenberg, A. Herz, R. Spanagel, R. Bals-Kubik, C. Stein, Ann. N. Y. Acad. Sci. 654, 347 (1992).
23. G. F. Koob, F. J. Vaccarino, M. Amalric, F. E. Bloom, in Brain Reward Systems and Abuse, J. Engel and L. Oreland, Eds. (Raven Press, New York, 1987), pp. 35-50; J. A. Engel et al., in Novel Pharmacological Interventions for Alcoholism, C. A. Naranjo and E. M. Sellers, Eds. (Springer, New York, 1992), pp. 68-82; E. M. Sellers, G. A. Higgins, M. B. Sobell, Trends Pharmacol. Sci. 13, 69 (1992); B. Tabakoff and P. L. Hoffman, in Substance Abuse: A Comprehensive Textbook, J. H. Lowinson, P. Ruiz, R. B. Millman, Eds. (Williams & Wilkins, Baltimore, 1992), pp. 152-185.
24. G. F. Koob, F. J. Vaccarino, M. Amalric, F. E. Bloom, in Brain Reward Systems and Abuse, J. Engel and L. Oreland, Eds. (Raven Press, New York, 1987), pp. 35-50; J. A. Engel et al., in Novel Pharmacological Interventions for Alcoholism, C. A. Naranjo and E. M. Sellers, Eds. (Springer, New York, 1992), pp. 68-82; E. M. Sellers, G. A. Higgins, M. B. Sobell, Trends Pharmacol. Sci. 13, 69 (1992); B. Tabakoff and P. L. Hoffman, in Substance Abuse: A Comprehensive Textbook, J. H. Lowinson, P. Ruiz, R. B. Millman, Eds. (Williams & Wilkins, Baltimore, 1992), pp. 152-185.
25. G. F. Koob, F. J. Vaccarino, M. Amalric, F. E. Bloom, in Brain Reward Systems and Abuse, J. Engel and L. Oreland, Eds. (Raven Press, New York, 1987), pp. 35-50; J. A. Engel et al., in Novel Pharmacological Interventions for Alcoholism, C. A. Naranjo and E. M. Sellers, Eds. (Springer, New York, 1992), pp. 68-82; E. M. Sellers, G. A. Higgins, M. B. Sobell, Trends Pharmacol. Sci. 13, 69 (1992); B. Tabakoff and P. L. Hoffman, in Substance Abuse: A Comprehensive Textbook, J. H. Lowinson, P. Ruiz, R. B. Millman, Eds. (Williams & Wilkins, Baltimore, 1992), pp. 152-185.
26. G. F. Koob, F. J. Vaccarino, M. Amalric, F. E. Bloom, in Brain Reward Systems and Abuse, J. Engel and L. Oreland, Eds. (Raven Press, New York, 1987), pp. 35-50; J. A. Engel et al., in Novel Pharmacological Interventions for Alcoholism, C. A. Naranjo and E. M. Sellers, Eds. (Springer, New York, 1992), pp. 68-82; E. M. Sellers, G. A. Higgins, M. B. Sobell, Trends Pharmacol. Sci. 13, 69 (1992); B. Tabakoff and P. L. Hoffman, in Substance Abuse: A Comprehensive Textbook, J. H. Lowinson, P. Ruiz, R. B. Millman, Eds. (Williams & Wilkins, Baltimore, 1992), pp. 152-185.
27. J. P. Chen, W. Paredes, J. H. Lowinson, E. L. Gardner, Neurosci. Lett. 129, 136 (1991); G. Tanda, F. E. Pontieri, G. Di Chiara, Science 276, 2048 (1997).
28. J. P. Chen, W. Paredes, J. H. Lowinson, E. L. Gardner, Neurosci. Lett. 129, 136 (1991); G. Tanda, F. E. Pontieri, G. Di Chiara, Science 276, 2048 (1997).
29. A. Markou and G. F. Koob, Neuropsychopharmacology 4, 17 (1991).
30. G. F. Koob, A. Markou, F. Weiss, G. Schulteis, Semin. Neurosci. 5, 351 (1993);
31. G. F. Koob, Neuron 16, 893 (1996).
32. Russell argued, "The notion of dependence on a drug, object, role, activity, or any other stimulus-source requires the crucial feature of negative affect experienced in its absence. The degree of dependence can be equated with the amount of this negative affect, which may range from mild discomfort to extreme distress, or it may be equated with the amount of difficulty or effort required to do without the drug, object, etc." This appearance of negative affect could have motivational significance or simply be a signal of a change in set point [M. A. H. Russell, in Drugs and Drug Dependence, G. Edwards, M. A. H. Russell, D. Hawks, M. MacCafferty, Eds. (Saxon House/Lexington Books, Westmead, UK, 1976), pp. 182-187].
33. M. R. A. Carrera, G. Schulteis, G. F. Koob, Neurosci. Abstr. 21, 725 (1995); A. J. Roberts, M. Cole, G. F. Koob, Alcohol. Clin. Exp. Res. 20, 1289 (1996).
34. M. R. A. Carrera, G. Schulteis, G. F. Koob, Neurosci. Abstr. 21, 725 (1995); A. J. Roberts, M. Cole, G. F. Koob, Alcohol. Clin. Exp. Res. 20, 1289 (1996).
35. A. Ettenberg, S. Sgro, N. White, Physiol. Behav. 28, 873 (1982).
36. C. K. Himmelsbach, Federation Proc. 2, 201 (1943).
37. In reference to opponent process theory, the a-processes (positive hedonic effects) were proposed to occur shortly after presentation of the reinforcer and to show tolerance. In contrast, the b-processes (negative hedonic effects) appear after the a-process has terminated, are slow to decay, and get larger with repeated exposure. More recent data and conceptualizations suggest that the b-process actually may appear shortly after the beginning of the a-process and may ultimately result in a change in hedonic set point (Fig. 4). In reference to sensitization theory, sensitization has been defined as the increased response to a drug that follows its repeated intermittent presentation and may be a potential source of significant differential vulnerability to certain concepts of the addiction cycle. Sensitization theory invokes a shift to a state of incentive salience (defined as a hypersensitive neural state that produces the experience of "wanting"). This state of incentive salience is hypothesized to be produced by drug-induced sensitization of the mesocorticolimbic dopamine system. Thus, the pathologically strong craving or "wanting" encountered during protracted abstinence would be hypothesized to be due, in large part, to an overactive mesocorticolimbic dopamine system. Sensitization has largely been characterized as an enhanced motor response to drugs of abuse with repeated administration, though recent work has extended these effects to a progressive increase in the reinforcing value of the drugs, at least during initial acquisition of drug-seeking or conditioned drug effects (Figs. 1 and 4). Sensitization is also more likely to be evident with intermittent, rather than continuous, administration of drugs, which favors the development of tolerance, and sensitization is long-lasting (up to weeks after injection) [R. L. Solomon and J. D. Corbit, Psychol. Rev. 81, 119 (1974); R. L. Solomon, in Psychopathology: Experimental Models, J. D. Maser and M. E. P. Seligman, Eds. (Freeman, San Francisco, 1977), pp. 124-145; T. E. Robinson and K. C. Berridge, Brain Res. Rev. 18, 247 (1993); G. Schulteis and G. F. Koob, Neurochem. Res. 21, 1437 (1996); J.-P. Laulin, A. Larcher, E. Celerier, M. Le Moal, G. Simonnet, Eur. J. Pharmacol., in press].
38. In reference to opponent process theory, the a-processes (positive hedonic effects) were proposed to occur shortly after presentation of the reinforcer and to show tolerance. In contrast, the b-processes (negative hedonic effects) appear after the a-process has terminated, are slow to decay, and get larger with repeated exposure. More recent data and conceptualizations suggest that the b-process actually may appear shortly after the beginning of the a-process and may ultimately result in a change in hedonic set point (Fig. 4). In reference to sensitization theory, sensitization has been defined as the increased response to a drug that follows its repeated intermittent presentation and may be a potential source of significant differential vulnerability to certain concepts of the addiction cycle. Sensitization theory invokes a shift to a state of incentive salience (defined as a hypersensitive neural state that produces the experience of "wanting"). This state of incentive salience is hypothesized to be produced by drug-induced sensitization of the mesocorticolimbic dopamine system. Thus, the pathologically strong craving or "wanting" encountered during protracted abstinence would be hypothesized to be due, in large part, to an overactive mesocorticolimbic dopamine system. Sensitization has largely been characterized as an enhanced motor response to drugs of abuse with repeated administration, though recent work has extended these effects to a progressive increase in the reinforcing value of the drugs, at least during initial acquisition of drug-seeking or conditioned drug effects (Figs. 1 and 4). Sensitization is also more likely to be evident with intermittent, rather than continuous, administration of drugs, which favors the development of tolerance, and sensitization is long-lasting (up to weeks after injection) [R. L. Solomon and J. D. Corbit, Psychol. Rev. 81, 119 (1974); R. L. Solomon, in Psychopathology: Experimental Models, J. D. Maser and M. E. P. Seligman, Eds. (Freeman, San Francisco, 1977), pp. 124-145; T. E. Robinson and K. C. Berridge, Brain Res. Rev. 18, 247 (1993); G. Schulteis and G. F. Koob, Neurochem. Res. 21, 1437 (1996); J.-P. Laulin, A. Larcher, E. Celerier, M. Le Moal, G. Simonnet, Eur. J. Pharmacol., in press].
39. In reference to opponent process theory, the a-processes (positive hedonic effects) were proposed to occur shortly after presentation of the reinforcer and to show tolerance. In contrast, the b-processes (negative hedonic effects) appear after the a-process has terminated, are slow to decay, and get larger with repeated exposure. More recent data and conceptualizations suggest that the b-process actually may appear shortly after the beginning of the a-process and may ultimately result in a change in hedonic set point (Fig. 4). In reference to sensitization theory, sensitization has been defined as the increased response to a drug that follows its repeated intermittent presentation and may be a potential source of significant differential vulnerability to certain concepts of the addiction cycle. Sensitization theory invokes a shift to a state of incentive salience (defined as a hypersensitive neural state that produces the experience of "wanting"). This state of incentive salience is hypothesized to be produced by drug-induced sensitization of the mesocorticolimbic dopamine system. Thus, the pathologically strong craving or "wanting" encountered during protracted abstinence would be hypothesized to be due, in large part, to an overactive mesocorticolimbic dopamine system. Sensitization has largely been characterized as an enhanced motor response to drugs of abuse with repeated administration, though recent work has extended these effects to a progressive increase in the reinforcing value of the drugs, at least during initial acquisition of drug-seeking or conditioned drug effects (Figs. 1 and 4). Sensitization is also more likely to be evident with intermittent, rather than continuous, administration of drugs, which favors the development of tolerance, and sensitization is long-lasting (up to weeks after injection) [R. L. Solomon and J. D. Corbit, Psychol. Rev. 81, 119 (1974); R. L. Solomon, in Psychopathology: Experimental Models, J. D. Maser and M. E. P. Seligman, Eds. (Freeman, San Francisco, 1977), pp. 124-145; T. E. Robinson and K. C. Berridge, Brain Res. Rev. 18, 247 (1993); G. Schulteis and G. F. Koob, Neurochem. Res. 21, 1437 (1996); J.-P. Laulin, A. Larcher, E. Celerier, M. Le Moal, G. Simonnet, Eur. J. Pharmacol., in press].
40. In reference to opponent process theory, the a-processes (positive hedonic effects) were proposed to occur shortly after presentation of the reinforcer and to show tolerance. In contrast, the b-processes (negative hedonic effects) appear after the a-process has terminated, are slow to decay, and get larger with repeated exposure. More recent data and conceptualizations suggest that the b-process actually may appear shortly after the beginning of the a-process and may ultimately result in a change in hedonic set point (Fig. 4). In reference to sensitization theory, sensitization has been defined as the increased response to a drug that follows its repeated intermittent presentation and may be a potential source of significant differential vulnerability to certain concepts of the addiction cycle. Sensitization theory invokes a shift to a state of incentive salience (defined as a hypersensitive neural state that produces the experience of "wanting"). This state of incentive salience is hypothesized to be produced by drug-induced sensitization of the mesocorticolimbic dopamine system. Thus, the pathologically strong craving or "wanting" encountered during protracted abstinence would be hypothesized to be due, in large part, to an overactive mesocorticolimbic dopamine system. Sensitization has largely been characterized as an enhanced motor response to drugs of abuse with repeated administration, though recent work has extended these effects to a progressive increase in the reinforcing value of the drugs, at least during initial acquisition of drug-seeking or conditioned drug effects (Figs. 1 and 4). Sensitization is also more likely to be evident with intermittent, rather than continuous, administration of drugs, which favors the development of tolerance, and sensitization is long-lasting (up to weeks after injection) [R. L. Solomon and J. D. Corbit, Psychol. Rev. 81, 119 (1974); R. L. Solomon, in Psychopathology: Experimental Models, J. D. Maser and M. E. P. Seligman, Eds. (Freeman, San Francisco, 1977), pp. 124-145; T. E. Robinson and K. C. Berridge, Brain Res. Rev. 18, 247 (1993); G. Schulteis and G. F. Koob, Neurochem. Res. 21, 1437 (1996); J.-P. Laulin, A. Larcher, E. Celerier, M. Le Moal, G. Simonnet, Eur. J. Pharmacol., in press].
41. In reference to opponent process theory, the a-processes (positive hedonic effects) were proposed to occur shortly after presentation of the reinforcer and to show tolerance. In contrast, the b-processes (negative hedonic effects) appear after the a-process has terminated, are slow to decay, and get larger with repeated exposure. More recent data and conceptualizations suggest that the b-process actually may appear shortly after the beginning of the a-process and may ultimately result in a change in hedonic set point (Fig. 4). In reference to sensitization theory, sensitization has been defined as the increased response to a drug that follows its repeated intermittent presentation and may be a potential source of significant differential vulnerability to certain concepts of the addiction cycle. Sensitization theory invokes a shift to a state of incentive salience (defined as a hypersensitive neural state that produces the experience of "wanting"). This state of incentive salience is hypothesized to be produced by drug-induced sensitization of the mesocorticolimbic dopamine system. Thus, the pathologically strong craving or "wanting" encountered during protracted abstinence would be hypothesized to be due, in large part, to an overactive mesocorticolimbic dopamine system. Sensitization has largely been characterized as an enhanced motor response to drugs of abuse with repeated administration, though recent work has extended these effects to a progressive increase in the reinforcing value of the drugs, at least during initial acquisition of drug-seeking or conditioned drug effects (Figs. 1 and 4). Sensitization is also more likely to be evident with intermittent, rather than continuous, administration of drugs, which favors the development of tolerance, and sensitization is long-lasting (up to weeks after injection) [R. L. Solomon and J. D. Corbit, Psychol. Rev. 81, 119 (1974); R. L. Solomon, in Psychopathology: Experimental Models, J. D. Maser and M. E. P. Seligman, Eds. (Freeman, San Francisco, 1977), pp. 124-145; T. E. Robinson and K. C. Berridge, Brain Res. Rev. 18, 247 (1993); G. Schulteis and G. F. Koob, Neurochem. Res. 21, 1437 (1996); J.-P. Laulin, A. Larcher, E. Celerier, M. Le Moal, G. Simonnet, Eur. J. Pharmacol., in press].
42. F. Weiss, A. Markou, M. T. Lorang, G. F. Koob, Brain Res. 593, 314 (1992); F. Weiss et al., J. Neurosci. 16, 3474 (1996).
43. F. Weiss, A. Markou, M. T. Lorang, G. F. Koob, Brain Res. 593, 314 (1992); F. Weiss et al., J. Neurosci. 16, 3474 (1996).
44. E. J. Nestler, J. Neurosci. 12, 2439 (1992).
45. _ and G. K. Aghajanian, Science 278, 58 (1997).
46. P. W. Kalivas and J. Stewart, Brain Res. Rev. 16, 223 (1991); F. J. White and M. E. Wolf, in The Biological Bases of Drug Tolerance and Dependence, J. A. Pratt, Ed. (Academic Press, London, 1991), pp. 153-197; D. J. Henry and F. J. White, Ann. N. Y. Acad. Sci. 654, 88 (1992).
47. P. W. Kalivas and J. Stewart, Brain Res. Rev. 16, 223 (1991); F. J. White and M. E. Wolf, in The Biological Bases of Drug Tolerance and Dependence, J. A. Pratt, Ed. (Academic Press, London, 1991), pp. 153-197; D. J. Henry and F. J. White, Ann. N. Y. Acad. Sci. 654, 88 (1992).
48. P. W. Kalivas and J. Stewart, Brain Res. Rev. 16, 223 (1991); F. J. White and M. E. Wolf, in The Biological Bases of Drug Tolerance and Dependence, J. A. Pratt, Ed. (Academic Press, London, 1991), pp. 153-197; D. J. Henry and F. J. White, Ann. N. Y. Acad. Sci. 654, 88 (1992).
49. D. H. Malin et al., Peptides 11, 277 (1990); T. S. Shippenberg, A. LeFevour, C. Heidbreder, J. Pharmacol. Exp. Ther. 276, 545 (1996).
50. D. H. Malin et al., Peptides 11, 277 (1990); T. S. Shippenberg, A. LeFevour, C. Heidbreder, J. Pharmacol. Exp. Ther. 276, 545 (1996).
51. The extended amygdala includes the medial (shell) part of the nucleus accumbens, bed nucleus of the stria terminalis, the central medial amygdala, and the sublenticular substantia innominata region. The afferent and efferent connections of the extended amygdala make it well situated for mediating not only basic drug reward, but also the neuroadaptive changes associated with sensitization and counter-adaptation. Afferent connections include projections from the limbic cortices, hippocampus, basolateral amygdala, midbrain, and lateral hypothalamus. Efferent connections include the ventral pallidum, ventral tegmental area, various brainstem projections, and a large projection to the lateral hypothalamus [J. B. Johnston, J. Comp. Neurol. 35, 337 (1923); G. F. Alheid and L. Heimer, Neuroscience 27, 1 (1988); L. Heimer and G. Alheid, in The Basal Forebrain: Anatomy to Function, T. C. Napier, P. W. Kalivas, I. Hanin, Eds. (Plenum, New York, 1991), pp. 1-42].
52. The extended amygdala includes the medial (shell) part of the nucleus accumbens, bed nucleus of the stria terminalis, the central medial amygdala, and the sublenticular substantia innominata region. The afferent and efferent connections of the extended amygdala make it well situated for mediating not only basic drug reward, but also the neuroadaptive changes associated with sensitization and counter-adaptation. Afferent connections include projections from the limbic cortices, hippocampus, basolateral amygdala, midbrain, and lateral hypothalamus. Efferent connections include the ventral pallidum, ventral tegmental area, various brainstem projections, and a large projection to the lateral hypothalamus [J. B. Johnston, J. Comp. Neurol. 35, 337 (1923); G. F. Alheid and L. Heimer, Neuroscience 27, 1 (1988); L. Heimer and G. Alheid, in The Basal Forebrain: Anatomy to Function, T. C. Napier, P. W. Kalivas, I. Hanin, Eds. (Plenum, New York, 1991), pp. 1-42].
53. The extended amygdala includes the medial (shell) part of the nucleus accumbens, bed nucleus of the stria terminalis, the central medial amygdala, and the sublenticular substantia innominata region. The afferent and efferent connections of the extended amygdala make it well situated for mediating not only basic drug reward, but also the neuroadaptive changes associated with sensitization and counter-adaptation. Afferent connections include projections from the limbic cortices, hippocampus, basolateral amygdala, midbrain, and lateral hypothalamus. Efferent connections include the ventral pallidum, ventral tegmental area, various brainstem projections, and a large projection to the lateral hypothalamus [J. B. Johnston, J. Comp. Neurol. 35, 337 (1923); G. F. Alheid and L. Heimer, Neuroscience 27, 1 (1988); L. Heimer and G. Alheid, in The Basal Forebrain: Anatomy to Function, T. C. Napier, P. W. Kalivas, I. Hanin, Eds. (Plenum, New York, 1991), pp. 1-42].
54. S. B. Caine, S. C. Heinrichs, V. L. Coffin, G. F. Koob, Brain Res. 692, 47 (1995); M. P. Epping-Jordan, A. Markou, G. F. Koob, Neurosci. Abstr. 21, 719 (1995); F. E. Pontieri, G. Tanda, G. Di Chiara, Proc. Natl. Acad. Sci. U.S.A. 92, 12304 (1995);
55. S. B. Caine, S. C. Heinrichs, V. L. Coffin, G. F. Koob, Brain Res. 692, 47 (1995); M. P. Epping-Jordan, A. Markou, G. F. Koob, Neurosci. Abstr. 21, 719 (1995); F. E. Pontieri, G. Tanda, G. Di Chiara, Proc. Natl. Acad. Sci. U.S.A. 92, 12304 (1995);
56. S. B. Caine, S. C. Heinrichs, V. L. Coffin, G. F. Koob, Brain Res. 692, 47 (1995); M. P. Epping-Jordan, A. Markou, G. F. Koob, Neurosci. Abstr. 21, 719 (1995); F. E. Pontieri, G. Tanda, G. Di Chiara, Proc. Natl. Acad. Sci. U.S.A. 92, 12304 (1995);
57. P. Hyytia and G. F. Koob, Eur. J. Pharmacol. 283, 151 (1995); C. J.Heyser, A. J. Roberts, G. Schulteis, P. Hyytia, G. F. Koob, Neurosci. Abstr. 21, 1698 (1995).
58. P. Hyytia and G. F. Koob, Eur. J. Pharmacol. 283, 151 (1995); C. J.Heyser, A. J. Roberts, G. Schulteis, P. Hyytia, G. F. Koob, Neurosci. Abstr. 21, 1698 (1995).
59. Y. Zhou et al., Eur. J. Pharmacol. 315, 31 (1996); Y. Zhou et al., J. Pharmacol. Exp. Ther. 279, 351 (1996).
60. Y. Zhou et al., Eur. J. Pharmacol. 315, 31 (1996); Y. Zhou et al., J. Pharmacol. Exp. Ther. 279, 351 (1996).
61. S. Rassnick, S. C. Heinrichs, K. T. Britton, G. F. Koob, Brain Res. 605, 25 (1993); S. C. Heinrichs, F. Menzaghi, G. Schulteis, G. F. Koob, L. Stinus, Behav. Pharmacol. 6, 74 (1995); F. Rodríguez de Fonseca, M. R. A. Carrera, M. Navarro, G. F. Koob, F. Weiss, Science 276, 2050 (1997); E. Merlo Pich et al., J. Neurosci. 15, 5439 (1995).
62. S. Rassnick, S. C. Heinrichs, K. T. Britton, G. F. Koob, Brain Res. 605, 25 (1993); S. C. Heinrichs, F. Menzaghi, G. Schulteis, G. F. Koob, L. Stinus, Behav. Pharmacol. 6, 74 (1995); F. Rodríguez de Fonseca, M. R. A. Carrera, M. Navarro, G. F. Koob, F. Weiss, Science 276, 2050 (1997); E. Merlo Pich et al., J. Neurosci. 15, 5439 (1995).
63. S. Rassnick, S. C. Heinrichs, K. T. Britton, G. F. Koob, Brain Res. 605, 25 (1993); S. C. Heinrichs, F. Menzaghi, G. Schulteis, G. F. Koob, L. Stinus, Behav. Pharmacol. 6, 74 (1995); F. Rodríguez de Fonseca, M. R. A. Carrera, M. Navarro, G. F. Koob, F. Weiss, Science 276, 2050 (1997); E. Merlo Pich et al., J. Neurosci. 15, 5439 (1995).
64. S. Rassnick, S. C. Heinrichs, K. T. Britton, G. F. Koob, Brain Res. 605, 25 (1993); S. C. Heinrichs, F. Menzaghi, G. Schulteis, G. F. Koob, L. Stinus, Behav. Pharmacol. 6, 74 (1995); F. Rodríguez de Fonseca, M. R. A. Carrera, M. Navarro, G. F. Koob, F. Weiss, Science 276, 2050 (1997); E. Merlo Pich et al., J. Neurosci. 15, 5439 (1995).
65. C. P. O'Brien, Science 278, 66 (1997).
66. H. deWit and J. Stewart, Psychopharmacology 75, 134 (1981); J. Stewart and H. deWit, in Assessing the Reinforcing Properties of Abused Drugs, M. A. Bozarth, Ed. (Springer-Verlag, New York, 1987), pp. 211-227; Y. Shaham, H. Rajabi, J. Stewart, J. Neurosci. 16, 1957 (1996).
67. H. deWit and J. Stewart, Psychopharmacology 75, 134 (1981); J. Stewart and H. deWit, in Assessing the Reinforcing Properties of Abused Drugs, M. A. Bozarth, Ed. (Springer-Verlag, New York, 1987), pp. 211-227; Y. Shaham, H. Rajabi, J. Stewart, J. Neurosci. 16, 1957 (1996).
68. H. deWit and J. Stewart, Psychopharmacology 75, 134 (1981); J. Stewart and H. deWit, in Assessing the Reinforcing Properties of Abused Drugs, M. A. Bozarth, Ed. (Springer-Verlag, New York, 1987), pp. 211-227; Y. Shaham, H. Rajabi, J. Stewart, J. Neurosci. 16, 1957 (1996).
69. S. S. O'Malley et al., Arch. Gen. Psychiatry 49, 881 (1992); J. R. Volpicelli, A. I. Alterman, M. Hayashida, C. P. O'Brien, ibid., p. 876; H. Sass, M. Soyka, K. Mann, W. Zieglgansberger, ibid. 53, 673 (1996).
70. S. S. O'Malley et al., Arch. Gen. Psychiatry 49, 881 (1992); J. R. Volpicelli, A. I. Alterman, M. Hayashida, C. P. O'Brien, ibid., p. 876; H. Sass, M. Soyka, K. Mann, W. Zieglgansberger, ibid. 53, 673 (1996).
71. S. S. O'Malley et al., Arch. Gen. Psychiatry 49, 881 (1992); J. R. Volpicelli, A. I. Alterman, M. Hayashida, C. P. O'Brien, ibid., p. 876; H. Sass, M. Soyka, K. Mann, W. Zieglgansberger, ibid. 53, 673 (1996).
72. J. R. Volpicelli, M. A. Davis, J. E. Olgin, Life Sci. 38, 841 (1986); R. Spanagel, S. M. Hoelter, K. Allingham, R. Landgraf, W. Zieglgansberger, Eur. J. Pharmacol. 305, 39 (1996); C. J. Heyser, G. Schulteis, P. Durbin, G. F. Koob, Neuropsychopharmacology, in press.
73. J. R. Volpicelli, M. A. Davis, J. E. Olgin, Life Sci. 38, 841 (1986); R. Spanagel, S. M. Hoelter, K. Allingham, R. Landgraf, W. Zieglgansberger, Eur. J. Pharmacol. 305, 39 (1996); C. J. Heyser, G. Schulteis, P. Durbin, G. F. Koob, Neuropsychopharmacology, in press.
74. J. R. Volpicelli, M. A. Davis, J. E. Olgin, Life Sci. 38, 841 (1986); R. Spanagel, S. M. Hoelter, K. Allingham, R. Landgraf, W. Zieglgansberger, Eur. J. Pharmacol. 305, 39 (1996); C. J. Heyser, G. Schulteis, P. Durbin, G. F. Koob, Neuropsychopharmacology, in press.
75. D. Smith, personal communication.
76. J. M. Murphy, W. J. McBride, L. Lumeng, T.-K. Li, Pharmacol. Biochem. Behav. 26, 389 (1987).
77. J. C. Crabbe and J. K. Belknap, Trends Pharmacol. Sci. 13, 212 (1992); L. H. Gold, Behav. Pharmacol. 7, 589 (1996); H. W. D. Matthes et al., Nature 383, 819 (1996).
78. J. C. Crabbe and J. K. Belknap, Trends Pharmacol. Sci. 13, 212 (1992); L. H. Gold, Behav. Pharmacol. 7, 589 (1996); H. W. D. Matthes et al., Nature 383, 819 (1996).
79. J. C. Crabbe and J. K. Belknap, Trends Pharmacol. Sci. 13, 212 (1992); L. H. Gold, Behav. Pharmacol. 7, 589 (1996); H. W. D. Matthes et al., Nature 383, 819 (1996).
80. M. J. Kreek, in Psychopharmacology: The Third Generation of Progress, H. Y. Meltzer, Ed. (Raven Press, New York, 1987), pp. 1597-1604.
81. P. V. Piazza and M. Le Moal, Annu. Rev. Pharmacol. Toxicol., 36, 359 (1996).
82. V. Deroche et al., Brain Res. 598, 343 (1992); P. V. Piazza and M. Le Moal, Brain Res. Rev., in press.
83. V. Deroche et al., Brain Res. 598, 343 (1992); P. V. Piazza and M. Le Moal, Brain Res. Rev., in press.
84. C. R. Schuster and T. Thompson, Annu. Rev. Pharmacol. Toxicol. 9, 483 (1969); M. E. Carroll, S. T. Lac, S. L. Nygaard, Psychopharmacology 97, 23 (1989).
85. C. R. Schuster and T. Thompson, Annu. Rev. Pharmacol. Toxicol. 9, 483 (1969); M. E. Carroll, S. T. Lac, S. L. Nygaard, Psychopharmacology 97, 23 (1989).
86. P. V. Piazza, J.-M. Deminiere, M. Le Moal, H. Simon, Science 245, 1511 (1989).
87. S. Cabib and S. Puglisi-Allegra, Psychopharmacology, 128, 331 (1996); A. R. Cools and M. Gingras Pharmacol. Biochem. Behav., in press.
88. S. Cabib and S. Puglisi-Allegra, Psychopharmacology, 128, 331 (1996); A. R. Cools and M. Gingras Pharmacol. Biochem. Behav., in press.
89. P. Sterling and J. Eyer, in Handbook of Life Stress Cognition and Health, S. Fisher and J. Reason, Eds. (Wiley, New York, 1988), pp. 629-649; B. S. McEwen and E. Stellar, Arch. Intern. Med. 153, 2093 (1993).
90. P. Sterling and J. Eyer, in Handbook of Life Stress Cognition and Health, S. Fisher and J. Reason, Eds. (Wiley, New York, 1988), pp. 629-649; B. S. McEwen and E. Stellar, Arch. Intern. Med. 153, 2093 (1993).
91. D. A. Bindra, A Theory of Intelligent Behavior (Wiley, New York, 1976).
92. M. J. Ellenhorn and D. G. Barceloux, Medical Toxicology: Diagnosis and Treatment of Human Poisoning (Elsevier, New York, 1988).
93. C. R. Cloninger, M. Bohman, S. Sigvardsson, Arch. Gen. Psychiatry 38, 861 (1981).
94. G. Schulteis, C. J. Heyser, G. F. Koob, Psychopharmacology 129, 56 (1997).
95. The concept of limited energy within a hedonic system can be traced at least as far back as Carl Jung, where the psyche was regarded as a relatively closed system. This limited energy was expressed by the term "libido," which basically described a general life instinct or psychic energy. Jung wrote, "Since our experience is confined to relatively closed systems, we are never in a position to observe an absolute psychological entropy, but the more the psychological system is closed off, the more clearly is the phenomenon of entropy manifested (a system is absolutely closed when no energy from outside can be fed into it)" [C. G. Jung, The Structure and Dynamics of the Psyche (translation from Über die Energetik der Seele [On the Driving Force of the Soul], vol. 8 of Über psychische Energetik und das Wasen der Traume [On Psychological Energy and the Meaning of Dreams] (Rascher, Zurich, 1948)} (Princeton Univ. Press, Princeton, NJ, ed. 2, 1969)].
96. The theological system of Calvin and his followers is marked by a strong emphasis on the sovereignty of God, the depravity of humankind, and the doctrine of predestination. Calvinism is characterized by a strict, disciplined lifestyle where morality is tantamount and there is a strong sense of church unity. Calvinists, and later Puritans, with regard to personal life, demanded of themselves a reformation of character, the rejection of idle recreations and vain display, and sober, obedient godliness [S. E. Ahlstrom, A Religious History of the American People (Yale Univ. Press, New Haven and London, 1972].
97. G. Schulteis, A. Markou, M. Cole, G. F. Koob, Proc. Natl. Acad. Sci. U.S.A. 92, 5880 (1995).
98. G. Schulteis, A. Markou, L. Gold, L. Stinus, G. F. Koob, J. Pharmacol. Exp. Ther. 271, 1391 (1994).
99. V. Deroche, M. Marinelli, M. Le Moal, P. V. Piazza, ibid. 281, 1401 (1997).
100. P. V. Piazza et al., Proc. Natl. Acad. Sci. U.S.A. 93, 8716 (1996).
101. Supported in part by NIH grants AA06420 and AA08459 (G.F.K.) from the National Institute of Alcohol Abuse and Alcoholism; NIH grants DA04043, DA04398, and DA08467 (G.F.K.) from the National Institute on Drug Abuse; and INSERM grants (M.L.M.). We thank the following individuals for their comments and discussions of the data and concepts discussed herein: S. Ahmed, M. Cador, V. Deroche, M. Heilig, C. Heyser, P. Karli, M. Lewis, A. Markou, P. Piazza, A. Roberts, G. Schulteis, G. Simonnet, T. Wall, and F. Weiss. We also thank P. Brennan, M. Arends, and the Molecular and Experimental Medicine Word Processing Unit (L. Miller and J. Robertson) for their help with manuscript preparation. This is manuscript number 11020-NP from The Scripps Research Institute.