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An opioid-like system regulating feeding behavior in C. elegans.

ABSTRACT: Neuropeptides are essential for the regulation of appetite. Here we show that neuropeptides could regulate feeding in mutants that lack neurotransmission from the motor neurons that stimulate feeding muscles. We identified nlp-24 by an RNAi screen of 115 neuropeptide genes, testing whether they affected growth. NLP-24 peptides have a conserved YGGXX sequence, similar to mammalian opioid neuropeptides. In addition, morphine and naloxone respectively stimulated and inhibited feeding in starved worms, but not in worms lacking NPR-17, which encodes a protein with sequence similarity to opioid receptors. Opioid agonists activated heterologously expressed NPR-17, as did at least one NLP-24 peptide. Worms lacking the ASI neurons, which express npr-17, did not response to naloxone. Thus, we suggest that Caenorhabditis elegans has an endogenous opioid system that acts through NPR-17, and that opioids regulate feeding via ASI neurons. Together, these results suggest C. elegans may be the first genetically tractable invertebrate opioid model.

SUBMITTER: Cheong MC

PROVIDER: S-EPMC4427864 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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An opioid-like system regulating feeding behavior in C. elegans.

Cheong Mi Cheong MC Artyukhin Alexander B AB You Young-Jai YJ Avery Leon L

eLife 20150421

Neuropeptides are essential for the regulation of appetite. Here we show that neuropeptides could regulate feeding in mutants that lack neurotransmission from the motor neurons that stimulate feeding muscles. We identified nlp-24 by an RNAi screen of 115 neuropeptide genes, testing whether they affected growth. NLP-24 peptides have a conserved YGGXX sequence, similar to mammalian opioid neuropeptides. In addition, morphine and naloxone respectively stimulated and inhibited feeding in starved wor ...[more]

PMID: 25898004

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Project description:PROBLEM/CONDITION:In 2017, a total of 70,237 persons in the United States died from a drug overdose, and 67.8% of these deaths involved an opioid. Historically, the opioid overdose epidemic in the United States has been closely associated with a parallel increase in opioid prescribing and with widespread misuse of these medications. National and state policy makers have introduced multiple measures to attempt to assess and control the opioid overdose epidemic since 2010, including improvements in surveillance systems. PERIOD COVERED:2010-2016 DESCRIPTION OF SYSTEM: The Prescription Behavior Surveillance System (PBSS) was created in 2011. Its goal was to track rates of prescribing of controlled substances and possible misuse of such drugs using data from selected state prescription drug monitoring programs (PDMP). PBSS data measure prescribing behaviors for prescription opioids using multiple measures calculated from PDMP data including 1) opioid prescribing, 2) average daily opioid dosage, 3) proportion of patients with daily opioid dosages ?90 morphine milligram equivalents, 4) overlapping opioid prescriptions, 5) overlapping opioid and benzodiazepine prescriptions, and 6) multiple-provider episodes. For this analysis, PBSS data were available for 2010-2016 from 11 states representing approximately 38.0% of the U.S. POPULATION:Average quarterly percent changes (AQPC) in the rates of opioid prescribing and possible opioid misuse measures were calculated for each state. RESULTS AND INTERPRETATION:Opioid prescribing rates declined in all 11 states during 2010-2016 (range: 14.9% to 33.0%). Daily dosage declined least (AQPC: -0.4%) in Idaho and Maine, and most (AQPC: -1.6%) in Florida. The percentage of patients with high daily dosage had AQPCs ranging from -0.4% in Idaho to -2.3% in Louisiana. Multiple-provider episode rates declined by at least 62% in the seven states with available data. Variations in trends across the 11 states might reflect differences in state policies and possible differential effects of similar policies. PUBLIC HEALTH ACTIONS:Use of PDMP data from individual states enables a more detailed examination of trends in opioid prescribing behaviors and indicators of possible misuse than is feasible with national commercially available prescription data. Comparison of opioid prescribing trends among states can be used to monitor the temporal association of national or state policy interventions and might help public health policymakers recognize changes in the use or possible misuse of controlled prescription drugs over time and allow for prompt intervention through amended or new opioid-related policies.

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An opioid-like system regulating feeding behavior in C. elegans.

Publications

An opioid-like system regulating feeding behavior in C. elegans.

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