A C. elegans Model of Nicotine-Dependent Behavior: Regulation by TRP-Family Channels

Abstract

Nicotine, the primary addictive substance in tobacco, induces profound behavioral responses in mammals, but the underlying genetic mechanisms are not well understood. Here we develop a C. elegans model of nicotine-dependent behavior. We show that worms exhibit behavioral responses to nicotine that parallel those observed in mammals, including acute response, tolerance, withdrawal, and sensitization. These nicotine responses require nicotinic acetylcholine receptor (nAChR) family genes that are known to mediate nicotine dependence in mammals, suggesting functional conservation of nAChRs in nicotine responses. Importantly, we find that mutant worms lacking TRPC (transient receptor potential canonical) channels are defective in their response to nicotine and that such a defect can be rescued by a human TRPC channel, revealing an unexpected role for TRPC channels in regulating nicotine-dependent behavior. Thus, C. elegans can be used to characterize known genes as well as to identify new genes regulating nicotine responses.

Identification by machine vision of the rate of motor activity decline as a lifespan predictor in C. elegans

“…Worms were analyzed for spontaneous locomotion behavior on NGM plates every other day throughout lifespan using an automated worm tracking system as previously described [6,24]. In brief, NGM plates were spread with a thin layer of freshly-grown bacteria (OP50) five minutes prior to tracking.…”

“…To explore this possibility, we quantified spontaneous locomotion behavior of 169 wild-type worms individually every other day throughout their lifespan. To do so, we utilized an automated worm tracking system that records worm movement and provides quantitative measurement of its activity such as locomotion speed in real time [6,24]. We found that the locomotion speed of these worms exhibited an exponential decay beginning as early as day 5 of adulthood ( Figure 1A).…”

Chronic nicotine exposure augments gustatory plasticity inCaenorhabditis elegans:involvement of dopamine signaling

“…elegans is also a model organism in studies to evaluate the effects of some drugs such as ethanol, 17,18) cocaine, 19) amphetamines, 20) and nicotine. [21][22][23] Ethanol administration interferes with gustatory plasticity in nematodes, i.e. salt chemotaxis learning, and serotonin signaling plays an essential role in this ethanol effect.…”

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

“…25 Furthermore, C. elegans show sensitivity and intoxication to different drugs such as alcohol, nicotine and certain antipsychotic drugs, display different forms of non-associative and associative learning, and present sleep-like states during the quiescence phase associated with the four molts. [26][27][28][29][30] The molecular and cellular mechanisms regulating these behaviors have revealed conserved features across species. For example, a worm model of nicotine addiction presenting acute and chronic behavioral responses that parallel those observed in mammals, has revealed a novel and important role of the conserved TRPC (transient receptor potential canonical) channels in modulating the activity of nicotinic acetylcholine receptors.…”

“…For example, a worm model of nicotine addiction presenting acute and chronic behavioral responses that parallel those observed in mammals, has revealed a novel and important role of the conserved TRPC (transient receptor potential canonical) channels in modulating the activity of nicotinic acetylcholine receptors. 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.…”