Drug-sensitive Reward in Crayfish: Exploring the Neural Basis of Addiction with Automated Learning Paradigms

Results of recent work from our labs and those of others have broadened perspectives on addiction beyond a human-specific, cognitive phenomenon. Addictive plant alkaloids are defensive compounds which have arisen to counter herbivory. With insects the true targets of the coevolutionary arms race, humans may be little more than collateral damage when impacted by 'human' drugs of abuse. The present paper summarizes recent contributions, with a primary focus on our own research in crayfish, where we characterize the behavioral and neural consequences resulting from chronic and acute exposure to psychostimulant and addictive drugs. Substituted phenethylamines, like amphetamine and cocaine, exhibit a wide range of effects in crayfish with direct parallels to those described from mammalian preparations. Unconditioned effects include intoxication and psychostimulation, where repeated exposure is accompanied by tolerance and sensitization, respectively. Psychostimulants exhibit powerful reinforcing properties in conditioned place preference, subject to extinction and reinstatement. Crayfish readily self-administer amphetamines using instrumental learning approaches. With a nervous system modular and uniquely accessible to neural probing, crayfish offer unique opportunities for studying the basic biological mechanisms of drug effects, for exploring how the appetitive disposition is implemented, and for examining how this is related to the rewarding action of drugs of abuse.