Invertebrate Models of Natural and Drug-Sensitive Reward

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Background

In mammals, rewarding properties of drugs depend on their capacity to activate appetitive motivational states. With the underlying mechanisms strongly conserved throughout metazoan evolution, invertebrate models have recently emerged as powerful new study systems in addiction research, offering a comparative and complementary approach. Modularly organized, genetically manipulatable, and experimentally accessible nervous systems render them uniquely suited for studying the basic biological mechanisms of drug effects, for exploring how the appetitive/seeking disposition is implemented in a simpler neural system, and for examining how such a disposition is related to the rewarding action of drugs of abuse. In addition, complete metamorphosis creates developmental stages with distinctly different morphologies and lifestyles, useful for exploring the effects of early drug exposure. This topic aims to contribute an evolutionary, comparative context to our understanding of a key component in learning, and of natural reward as an important life-sustaining process. Crayfish, honey bees, fruit flies, nematodes, and many other invertebrate taxa exhibit strong responses to common psychostimulants and their natural reward circuits prove surprisingly sensitive to human drugs of abuse. With many levels of neural, genetic, and molecular organization uniquely accessible, the application of learning paradigms (comparable to those traditionally used in vertebrate studies) opens rich new avenues of research into the basic biological mechanisms of drug addiction. The development of advanced genetic and physiological tools in Drosophila, to directly manipulate neural systems in the living animal, is an excellent example. Moreover new approaches for studying properties at the level of synapses allows unique insights into changes that accompany drug use and abuse. The time is now right to comprehensively review the status and recent advancements in this area of research, and to share these insights with the wider research community.

In a series of papers we examine the current state of research arranged according to behavioral criteria matching those from the mammalian literature on addiction. For this research topic we welcome submissions for work that (1) explores natural reward systems in invertebrates, and the integral roles they play in learning; (2) demonstrates activational effects associated with a range of common psychostimulants; (3) reviews how repeated application elicits psychostimulant sensitization; (4) explores how reward strength for individual drugs is assessed via conditioned place preference and operant, self-administration paradigms; and (5) concludes the volume with a discussion of extinction, withdrawal, reinstatement, and potential therapeutic targets.

Keywords: Psychostimulant, learning, dopamine, addiction, alkaloids

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