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Piazza and M. Le Moal, Brain Res. Rev., in press. 42. 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). 43. P. V. Piazza, J.-M. Deminiere, M. Le Moal, H. Simon, Science 245, 1511 (1989). 44. S. Cabib and S. Puglisi-Allegra, Psychopharmacology, 128, 331 (1996); A. R. Cools and M. Gingras Pharmacol. Biochem. Behav., in press. 45. 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). 46. D. A. Bindra, A Theory of Intelligent Behavior ( Wiley, New York, 1976). 47. M. J. Ellenhorn and D. G. Barceloux, Medical Toxicology: Diagnosis and Treatment of Human Poisoning (Elsevier, New York, 1988). 48. C. R. Cloninger, M. Bohman, S. Sigvardsson, Arch. Gen. Psychiatry 38, 861 (1981). 49. G. Schulteis, C. J. Heyser, G. F. Koob, Psychopharmacology 129, 56 (1997). 50. 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)]. 51. 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]. 52. G. Schulteis, A. Markou, M. Cole, G. F. Koob, Proc. Natl. Acad. Sci. U.S.A. 92, 5880 (1995). 53. G. Schulteis, A. Markou, L. Gold, L. Stinus, G. F. Koob, J. Pharmacol. Exp. Ther. 271, 1391 (1994). 54. V. Deroche, M. Marinelli, M. Le Moal, P. V. Piazza, ibid. 281, 1401 (1997). 55. P. V. Piazza et al., Proc. Natl. Acad. Sci. U.S.A. 93, 8716 (1996). 56. 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.