Characterization of a novel D2‐like dopamine receptor with a truncated splice variant and a D1‐like dopamine receptor unique to invertebrates from <i>Caenorhabditis elegans</i>

Sugiura, M.; Fuke, Satoshi; Suo, Satoshi; Sasagawa, Noboru; Tol, Hubert H.M. Van; Ishiura, Shoichi

doi:10.1111/j.1471-4159.2005.03268.x

Cited by 72 publications

(84 citation statements)

References 34 publications

(51 reference statements)

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“…DOP-4 receptors have been shown to localize in GABA AVL motoneurons, the PQR chemosensory neurons, and other head neurons (Sugiura et al, 2005). Although we do not know whether the C. elegans DA neurons make synapses with neurons expressing DOP-4 receptors, we cannot exclude the possibility that the release of large amounts of extracellular DA after AMPH treatment may lead to spillover of the neurotransmitter to extrasynaptic sites.…”

Section: Discussionmentioning

confidence: 72%

“…To date, four DA receptors have been cloned and functionally characterized in C. elegans: the D1-like DA receptors DOP-1 and DOP-4 (Suo et al, 2002;Sugiura et al, 2005); and the D2-like DA receptors DOP-2 and DOP-3 (Suo et al, 2003;Chase et al, 2004;Sugiura et al, 2005). We investigated the involvement of these receptors in AMPH-induced SWIP using knockout lines for each receptor.…”

Section: Amph-induced Swip Requires Dat-1 Expressionmentioning

confidence: 99%

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Molecular Mechanisms of Amphetamine Actions in Caenorhabditis elegans

Carvelli

Matthies²,

Galli³

2010

Mol Pharmacol

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Amphetamine (AMPH) poses a serious hazard to public health. Defining the molecular targets of AMPH is essential to developing treatments for psychostimulant abuse. AMPH elicits its behavioral effects primarily by increasing extracellular dopamine (DA) levels through the reversal of the DA transporter (DAT) cycle and, as a consequence, altering DA signaling. In Caenorhabditis elegans, an excess of synaptic DA results in a loss of motility in water, termed swimming-induced paralysis (SWIP). Here we demonstrate that AMPH produces SWIP in a time-and dose-dependent manner in wild-type (wt) animals but has a reduced ability to generate SWIP in DAT knock out worms (dat-1). To determine whether D1-like and/or D2-like receptors are involved in AMPH-induced SWIP, we performed experiments in DOP-1 and DOP-4, and DOP-2, and DOP-3 receptor knockout animals, respectively. AMPH administration resulted in a reduced ability to induce SWIP in animals lacking DOP-3, DOP-4, and DOP-2 receptors. In contrast, in worms lacking DOP-1 receptors, AMPH-induced SWIP occurred at wt levels. Using microamperometry on C. elegans DA neurons, we determined that in contrast to wt cells, AMPH failed to promote DA efflux in dat-1 DA neurons. These data suggest that DA efflux is critical to sustaining SWIP behavior by signaling through DOP-3, DOP-4, and DOP-2. In a double mutant lacking both DAT-1 and DOP-1 expression, we found no ability of AMPH to induce SWIP or DA efflux. This result supports the paradigm that DA efflux through C. elegans DAT is required for AMPH-induced behaviors and does not require DOP-1 signaling.Dysfunction in DA signaling has been implicated in multiple pathologies, including schizophrenia, attention-deficit/ hyperactivity disorder, Parkinson's disease, and AMPH abuse. Although it is well known that dopaminergic pathways are involved in cocaine and AMPH abuse, a comprehensive understanding of the key players coordinating AMPH behaviors is still missing. Upon exocytotic release of DA into the synapse, DATs coordinate the spatial and temporal action of DA by actively clearing the amine from the extracellular space. Although diffusion and enzymatic degradation may partially govern the synaptic concentration of DA, knockout studies have established DAT function as the primary mechanism controlling extracellular DA levels. DAT is the major molecular target responsible for the reward properties and abuse potential of several psychostimulants, including cocaine, methamphetamine, and AMPH. As a substrate of DAT, AMPH elevates extracellular DA levels by antagonizing DA clearance and stimulating DAT-mediated DA efflux. The subsequent increase in dopaminergic signaling mediated by DA receptors leads to secondary plasticity that mediates addiction. Whereas multiple lines of evidence implicate DA receptors in the mechanism of action of abused psychostimulants such as AMPH (Hiroi and White, 1991;Vallone et al., 2000;Ball et al., 2003), the degree to which different receptors support AMPH-induced behaviors has not yet been complet...

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Section: Discussionmentioning

confidence: 72%

Section: Amph-induced Swip Requires Dat-1 Expressionmentioning

confidence: 99%

Molecular Mechanisms of Amphetamine Actions in Caenorhabditis elegans

Carvelli

Matthies²,

Galli³

2010

Mol Pharmacol

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“…The opposite effects of D1 and D2 signaling on adenylyl cyclase activity suggest a simple model to explain the antagonistic effects of coexpressed DA receptor signaling; however, whether or not this antagonism occurs within a single cell remains largely untested. When tested in cell culture experiments, DOP-1 and DOP-3 receptors can increase and decrease cAMP levels, respectively (Sanyal et al 2004;Sugiura et al 2005), but this is not the coupling that we have identified in vivo despite the fact that Gas is expressed in the cholinergic motor neurons and is thus available for coupling to the DOP-1 receptor (Korswagen et al 1997).…”

Section: D1-like Receptors Can Act Through Gaq and D2-like Receptorsmentioning

confidence: 93%

Coexpressed D1- and D2-Like Dopamine Receptors Antagonistically Modulate Acetylcholine Release in Caenorhabditis elegans

Allen¹,

Maher

Wani

et al. 2011

Genetics

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Dopamine acts through two classes of G protein-coupled receptor (D1-like and D2-like) to modulate neuron activity in the brain. While subtypes of D1-and D2-like receptors are coexpressed in many neurons of the mammalian brain, it is unclear how signaling by these coexpressed receptors interacts to modulate the activity of the neuron in which they are expressed. D1-and D2-like dopamine receptors are also coexpressed in the cholinergic ventral-cord motor neurons of Caenorhabditis elegans. To begin to understand how coexpressed dopamine receptors interact to modulate neuron activity, we performed a genetic screen in C. elegans and isolated mutants defective in dopamine response. These mutants were also defective in behaviors mediated by endogenous dopamine signaling, including basal slowing and swimming-induced paralysis. We used transgene rescue experiments to show that defects in these dopamine-specific behaviors were caused by abnormal signaling in the cholinergic motor neurons. To investigate the interaction between the D1-and D2-like receptors specifically in these cholinergic motor neurons, we measured the sensitivity of dopamine-signaling mutants and transgenic animals to the acetylcholinesterase inhibitor aldicarb. We found that D2 signaling inhibited acetylcholine release from the cholinergic motor neurons while D1 signaling stimulated release from these same cells. Thus, coexpressed D1-and D2-like dopamine receptors act antagonistically in vivo to modulate acetylcholine release from the cholinergic motor neurons of C. elegans.

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“…The differences in indices between the alleles of the same gene may be caused by side mutation(s) in each of the mutant strains. Although the incomplete suppression of enhancement by dop-3 mutation may suggest the involvement of another dopamine receptor, invertebrate-specific dopamine receptor homolog dop-4(tm1392) (Sugiura et al, 2005) did not appear to be involved as a single mutation or double mutation with dop-3 (K. F. and K. D. K., unpublished observation). Together, these results suggest that D 2 -like dop-3 plays a significant role in the enhancement of 2-nonanone avoidance.…”

Section: Dopamine Signaling Is Required For the Enhancement Of 2-nonamentioning

confidence: 99%

Enhancement of Odor Avoidance Regulated by Dopamine Signaling inCaenorhabditis elegans

Kimura¹,

Fujita²,

Izui³

2010

J. Neurosci.

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The enhancement of sensory responses after prior exposure to a stimulus is a fundamental mechanism of neural function in animals. Its molecular basis, however, has not been studied in as much depth as the reduction of sensory responses, such as adaptation or habituation. We report here that the avoidance behavior of the nematode Caenorhabditis elegans in response to repellent odors (2-nonanone or 1-octanol) is enhanced rather than reduced after preexposure to the odors. This enhancement effect of preexposure was maintained for at least 1 h after the conditioning. The enhancement of 2-nonanone avoidance was not dependent on the presence or absence of food during conditioning, which generally functions as a strong positive or negative unconditioned stimulus in the animals. These results suggest that the enhancement is acquired as a type of nonassociative learning. In addition, genetic and pharmacological analyses revealed that the enhancement of 2-nonanone avoidance requires dopamine signaling via D 2 -like dopamine receptor DOP-3, which functions in a pair of RIC interneurons to regulate the enhancement. Because dopamine signaling has been tightly linked with food-related information to modulate various behaviors of C. elegans, it may play different role in the regulation of the enhancement of 2-nonanone avoidance. Thus, our data suggest a new genetic and pharmacological paradigm for nonassociative enhancement of neural responses that is regulated by dopamine signaling.

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Characterization of a novel D2‐like dopamine receptor with a truncated splice variant and a D1‐like dopamine receptor unique to invertebrates from Caenorhabditis elegans

Cited by 72 publications

References 34 publications

Molecular Mechanisms of Amphetamine Actions in Caenorhabditis elegans

Molecular Mechanisms of Amphetamine Actions in Caenorhabditis elegans

Coexpressed D1- and D2-Like Dopamine Receptors Antagonistically Modulate Acetylcholine Release in Caenorhabditis elegans

Enhancement of Odor Avoidance Regulated by Dopamine Signaling inCaenorhabditis elegans

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