Animal Models of Opiate Dependence

  • Rafael Maldonado
  • Luis Stinus
  • George F. Koob
Part of the Neuroscience Intelligence Unit book series (NIU.LANDES)


Endogenous opioid peptides exert a wide range of central and peripheral effects. It was thought that tolerance to opiates could be assessed for any of its measurable actions. However, tolerance develops to many different effects of morphine, to different degrees and at different rates. Moreover, some effects seem to be unchanged while others increase after repeated opiate administration. Thus, these adaptive mechanisms, which develop for each morphine effect, must not have absolute common bases. They must depend upon the interaction between the overstimulation of opioid receptors by opiates and the complex neuronal circuitries responsible for the physiological effects. It is important to emphasize that these adaptive processes are mediated through physiological feedback mechanisms. Following the repeated exposure to the drug, their activities will increase out of the physiological range, and this situation will become progressively permanent and will establish a new artificial homeostatic equilibrium of the “milieu interieur,” in which the opiate will exert a controlling role in the sense that the permanent stimulation of opiate receptors is now needed. In opiate-addicted subjects, abstinence of the drug will disrupt this artificial homeostatic state triggering physiological, behavioral and psychological effects. Together, these symptoms will define opiate dependence. Thus, one must consider that when a subject is tolerant or sensitized to a given drug effect, the subject is dependent on the drug as a whole.


Neurobiological Mechanism Chronic Morphine Opiate Withdrawal Conditioned Place Aversion Somatic Sign 
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Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • Rafael Maldonado
    • 1
  • Luis Stinus
    • 2
  • George F. Koob
    • 3
  1. 1.Pharmacochimie Moléculaire et StructuraleParisFrance
  2. 2.Université de Bordeaux IIBordeaux CédexFrance
  3. 3.The Scripps Research InstituteLa JollaUSA

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