Increasing evidence that ordinary cues paired with reward can acquire value indicates that the incentive properties of rewards are capable of being transferred onto cues, making them incentive stimuli. Studies have begun focusing on isolating components of the reward circuit involved in imparting incentive salience onto a cue with the goal of identifying rats with susceptibilities to drug addiction. Such studies have found that under a Pavlovian Conditioned Approach (PCA) paradigm, sign-tracking rats are at increased risk for instilling incentive salience onto conditioned stimuli and for engaging in drug-related behavior. With better understanding of the neural basis of sign tracking and its behavioral aspect of drug seeking comes a better chance of discovering treatment methods for drug addiction. This study examines the potential behavioral outcomes of altering the pathway starting in the Ventral Pallidum (VP) and ending in the Ventral Tegmental Area (VTA) by using Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). While there is some evidence of an interaction between the effects of DREADDs on this neural circuit and behavior, not all results presented here reach significance. Additional studies are needed to confirm the hypothesis of specific inhibitory DREADDs from the VP to the VTA causing increased amounts of sign tracking in rats as a way to assess whether this pathway is implicated in predisposing rats to sign-tracking behavior. / 2018-07-11T00:00:00Z

G-protein signalling is an evolutionary conserved concept highlighting its fundamental impact on developmental and functional processes. Studies on the effects of G protein signals on tissues as well as an entire organism are often conducted in Caenorhabditis elegans. To understand and control dynamics and kinetics of the processes involved, pharmacological modulation of specific G protein pathways would be advantageous, but is difficult due to a lack in accessibility and regulation. To provide this option, we designed G protein-coupled receptor-based designer receptors (DREADDs) for C. elegans. Initially described in mammalian systems, these modified muscarinic acetylcholine receptors are activated by the inert drug clozapine N-oxide, but not by their endogenous agonists. We report a novel C. elegans-specific DREADD, functionally expressed and specifically activating Gq-protein signalling in vitro and in vivo which we used for modulating mating behaviour. Therefore, this novel designer receptor demonstrates the possibility to pharmacologically control physiological functions in C. elegans.

G-protein signalling is an evolutionary conserved concept highlighting its fundamental impact on developmental and functional processes. Studies on the effects of G protein signals on tissues as well as an entire organism are often conducted in Caenorhabditis elegans. To understand and control dynamics and kinetics of the processes involved, pharmacological modulation of specific G protein pathways would be advantageous, but is difficult due to a lack in accessibility and regulation. To provide this option, we designed G protein-coupled receptor-based designer receptors (DREADDs) for C. elegans. Initially described in mammalian systems, these modified muscarinic acetylcholine receptors are activated by the inert drug clozapine N-oxide, but not by their endogenous agonists. We report a novel C. elegans-specific DREADD, functionally expressed and specifically activating Gq-protein signalling in vitro and in vivo which we used for modulating mating behaviour. Therefore, this novel designer receptor demonstrates the possibility to pharmacologically control physiological functions in C. elegans.