Crayfish Learning: Addiction and the Ganglionic Brain.

Recognizing addiction as a phenomenon with deep evolutionary roots grants valuable new perspectives into understanding its behavioral features, as well as its underlying neural mechanisms and genetic architecture. Although now generally misbranded as "human drugs of abuse," addictive plant alkaloids originally arose as potent chemical defenses against insect herbivory. The products of this evolutionary arms race, compounds such as nicotine, cathinone, or morphine, target essential biological mechanisms for motivation and learning and act as weaponized disruptors. Human vulnerabilities to these addictive drugs may thus represent little more than collateral damage arising from deep homology, i.e., shared biological implementation of behavioral functions with taxa that trace back to the early divergence of bilateral metazoans. Consistent with such a view, invertebrate preparations exhibit a rich spectrum of behavioral and neural consequences in response to drug exposure. Although there is certainly evidence for addiction-like phenomena in many invertebrate lineages, the present review focuses attention primarily on our recent work in crayfish. Using this decapod crustacean model, we have characterized a range of amphetamines, cathinones, and opioids for evidence of unconditioned intoxication, sympathomimetic properties, psychostimulant sensitization, conditioned cue learning, and operant self-administration. Overall, our findings on drug-sensitive reward in crayfish bear striking similarities to equivalent phenomena illustrated in mammals. Experimentally tractable invertebrate models may thus provide fundamental insights into the homo- and paralogous mechanisms mediating responses to addictive drugs, while illuminating the limits of such contrasts.