Invertebrate models of drug abuse

Abstract

Susceptibility to drug addiction depends on genetic and environmental factors and their complex interactions. Studies with mammalian models have identified molecular targets, neurochemical systems, and brain regions that mediate some of the addictive properties of abused drugs. Yet, our understanding of how the primary effects of drugs lead to addiction remains incomplete. Recently, researchers have turned to the invertebrate model systems Drosophila melanogaster and Caenorhabditis elegans to dissect the mechanisms by which abused drugs modulate behavior. Due to their sophisticated genetics, relatively simple anatomy, and their remarkable molecular similarity to mammals, these invertebrate models should provide useful insights into the mechanisms of drug action. Here we review recent behavioral and genetic studies in flies and worms on the effects of ethanol, cocaine, and nicotine, three of the most widely abused drugs in the world.

Ethological analyses of crayfish behavior: a new invertebrate system for measuring the rewarding properties of psychostimulants

“…[64]). The present results have gone on to demonstrate that studies of reward are well within the scope of invertebrate psychostimulant studies.…”

“…[64]), naturalistic interpretations of crayfish drug reward may derive from evolutionary and ecological considerations. For example, it will be important to study the mechanisms by which amphetamine infusions are able to be ~two-fold more effective than cocaine infusions for crayfish CPP.…”

“…And finally, neurophysiological investigations in decapod crustaceans are not restricted to the neuromuscular junction as they have been in flies and worms (see ref. [64]), but rather can be carried out on monoaminergic neurons that can be reliably identified between different subjects (e.g., ref. [24]).…”

Lithium- and Valproate-Induced Alterations in Circadian Locomotor Behavior in Drosophila

“…Although not nearly as complex in its behavioral repertoire as higher mammals, Drosophila is an excellent model organism that blends genetic accessibility and behavioral complexity. Drosophila has been successfully used in dissecting genetic components of behavioral paradigms including associative learning and memory (DeZazzo and Tully, 1995), substance abuse (Wolf, 1999;Wolf and Heberlein, 2003), circadian behavior (Wang and Sehgal, 2002), and recently sleep (Hendricks et al, 2001;Shaw et al, 2002). It is also very suitable for the study of gene interactions and epistasis.…”

Big ideas for small brains: what can psychiatry learn from worms, flies, bees and fish?

“…26 The links between dopaminergic pathways and addictive behavior have been examined in C. elegans. 31,32 In a C. elegans model of ethanol intoxication, activation of a BK potassium channel, SLO-1, has been shown to have a central role in the acute neurobehavioral effects of this substance. 27 A recent study has revealed the important role that CRH-1, the C. elegans homolog of CREB, has on the worm's foraging rate through regulation of tph-1 (tryptophan hydroxylase), which is necessary for serotonin production.…”