Role of serotonergic and adrenergic systems in alcohol tolerance

Abstract

• 1.

  1. This paper attempts to provide an overview of our research which has led us to the concept of tolerance as adaptation to drug effects rather than adaptation to the drug itself.

• 2.

  2. This notion can be expanded to include drug tolerance as an example of a range of adaptive manifestations of neuroplasticity.

• 3.

  3. The suggestion that serotonin (5-HT) is involved in general adaptive processes gave impetus to exploration of its role in tolerance.

• 4.

  4. The paper focusses, therefore, primarily on the line of research that started with whole brain manipulation of brain 5-HT and evolved into a study of the effects of discrete and localized depletion of 5-HT.

• 5.

  5. The evidence for the role of median raphe nucleus, the limbic 5-HT, central norepinephrine (NE), and Des-Gly⁹ (Arg⁸) vasopressin (DGAVP) in ethanol tolerance is also provided, with the relationship between the median raphe nuclei and the limbic system most clearly delineated.