Drug-activation of brain reward pathways

Abstract

A wide variety of biologically important stimuli can serve as rewards and establish adaptive behavior patterns in higher animals. Such stimuli act through brain mechanisms that evolved long before the human invention of the hypodermic syringe, the human harnessing of fire, or the human development of methods for refining and concentrating psychoactive substances that occur in nature. These brain mechanisms utilize endogenous neurotransmitters that are blocked or mimicked by a variety of addictive exogenous substances. The brain mechanisms for feeding, for example, have depended on endogenous opioid peptide neurotransmitters from the earliest stages Ž of our evolutionary history Josefsson and Johansson, . 1979; Kavaliers and Hirst, 1987 . A complete understanding of the brain mechanisms of addiction will require an understanding of the anatomy and normal functions of brain pathways that evolved because they served basic adaptive functions. Our current understanding of the brain circuitry through which various rewards gain control over behavior has developed from studies of brain stimulaŽ . tion reward Olds and Milner, 1954 . Rewarding brain stimulation is useful in anatomical localization of reward-relevant circuit elements because focal electrical stimulation of the brain only activates nerve fibers passing within a fraction of a millimetre of the elecŽ . trode tip Fouriezos and Wise, 1984 . However, while stimulation differentially activates fibers of different sizes, the stimulation is indiscriminate with respect to the neurotransmitter a given set of fibers carry. Thus our knowledge of the neurochemical subtypes of reward-relevant neurons derives primarily from pharmacological studies; the rewarding effects of brain stimulation can be attenuated or augmented by drugs that are selective for various neurotransmitter sysŽ . tems Wise and Rompre, 1989 , and neurochemically selective drugs can be rewarding in their own right Ž . Wise, 1978 . Moreover, laboratory animals can be trained to self-administer drugs injected directly into Ž . the brain Bozarth and Wise, 1981 ; such injections are, to a significant degree, both anatomically and neurochemically selective.