Conditioned Opioid Withdrawal Decreases Nociceptin/Orphanin FQ Levels in the Frontal Cortex and Olfactory Tubercle

Walker, John R.; Terenius, Lars; Koob, George F.

doi:10.1016/s0893-133x(02)00292-0

Cited by 13 publications

(5 citation statements)

References 30 publications

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“…For opioids, intraventricular injections of nociceptin inhibited naloxone-precipitated withdrawal signs in morphine-dependent rats (Kotlinska et al, 2000, Kotli nska et al, 2004, and conditioned withdrawal (measured by place aversion) increased nociceptin levels (measured by a radioimmunoassay) in the frontal cortex (Walker et al, 2002). Intracerebroventricular nociceptin administration did not block heroin selfadministration in nondependent rats, but a nociceptin receptor agonist decreased intravenous remifentanil self-administration in rats and rhesus monkeys (Podlesnik et al, 2011;Sukhtankar et al, 2014).…”

Section: B Nociceptinmentioning

confidence: 99%

Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development

2020

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Compulsive drug seeking that is associated with addiction is hypothesized to follow a heuristic framework that involves three stages (binge/intoxication, withdrawal/negative affect, and preoccupation/ anticipation) and three domains of dysfunction (incentive salience/pathologic habits, negative emotional states, and executive function, respectively) via changes in the basal ganglia, extended amygdala/habenula, and frontal cortex, respectively. This review focuses on neurochemical/neurocircuitry dysregulations that contribute to hyperkatifeia, defined as a greater intensity of negative emotional/motivational signs and symptoms during withdrawal from drugs of abuse in the withdrawal/negative affect stage of the addiction cycle. Hyperkatifeia provides an additional source of motivation for compulsive drug seeking via negative reinforcement. Negative reinforcement reflects an increase in the probability of a response to remove an aversive stimulus or drug seeking to remove hyperkatifeia that is augmented by genetic/epigenetic vulnerability, environmental trauma, and psychiatric comorbidity. Neurobiological targets for hyperkatifeia in addiction involve neurocircuitry of the extended amygdala and its connections via within-system neuroadaptations in dopamine, enkephalin/endorphin opioid peptide, and g-aminobutyric acid/glutamate systems and between-system neuroadaptations in prostress corticotropin-releasing factor, norepinephrine, glucocorticoid, dynorphin, hypocretin, and neuroimmune systems and antistress neuropeptide Y, nociceptin, endocannabinoid, and oxytocin systems. Such neurochemical/ neurocircuitry dysregulations are hypothesized to mediate a negative hedonic set point that gradually gains allostatic load and shifts from a homeostatic hedonic state to an allostatic hedonic state. Based on preclinical studies and translational studies to date, medications and behavioral therapies that reset brain stress, antistress, and emotional pain systems and return them to homeostasis would be promising new targets for medication development.Significance Statement--The focus of this review is on neurochemical/neurocircuitry dysregulations that contribute to hyperkatifeia, defined as a greater intensity of negative emotional/motivational signs and symptoms during withdrawal from drugs of abuse in the withdrawal/ negative affect stage of the drug addiction cycle and a driving force for negative reinforcement in addiction. Medications and behavioral therapies that reverse hyperkatifeia by resetting brain stress, antistress, and emotional pain systems and returning them to homeostasis would be promising new targets for medication development.

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Section: B Nociceptinmentioning

confidence: 99%

Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development

2020

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“…The procedure for peptide extraction has been described previously (Walker et al, 2002) and modified. After TFL was determined in the 6th day, rats were anesthetized as described above.…”

Section: Methodsmentioning

confidence: 99%

Sex differences in the Nociceptin/Orphanin FQ system in rat spinal cord following chronic morphine treatment

2012

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Nociceptin/Orphanin FQ (N/OFQ) appears to contribute to the development of morphine tolerance, as blockade of its actions will block or reverse the process. To better understand the contribution of N/OFQ to the development of morphine tolerance, this study examined the effect of chronic morphine treatment on levels of N/OFQ and levels and activity of the N/OFQ peptide (NOP) receptor in spinal cord (SC) from male and female rats. Both male and female Wistar rats showed less responsiveness to morphine after subcutaneous injection of escalating doses of morphine (10, 20, 40, 60 and 80 mg/kg, respectively) twice daily for five consecutive days. Male rats were more tolerant to the antinociceptive actions of morphine than females. The N/OFQ content of SC extracts was higher in females than in males, regardless of treatment; following chronic morphine treatment the difference in N/OFQ levels between males and females was more pronounced. N/OFQ content in cerebrospinal fluid (CSF) was reduced 40% in male and 16% in female rats with chronic morphine exposure, but increased in periaqueductal grey of both sexes. Chronic morphine treatment increased NOP receptor levels 173% in males and 137% in females, while decreasing affinity in both. Chronic morphine increased the efficacy of N/OFQ-stimulated [35S]GTPγS binding to SC membranes from male rats, consistent with increased receptor levels. Taken together, these findings demonstrate sex differences in N/OFQ–NOP receptor expression and NOP receptor activity following chronic morphine treatment. They also suggest interplay between endogenous N/OFQ and chronic morphine treatment that results in nociceptive modulation.

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“…23 Apart from its roles in the VTA-NAc and ARC circuits, N/OFQ can also inhibit mPFC-projecting VTA neurons 24 and a reduction in mPFC N/OFQ level was reported in rodents that underwent conditioned opioid withdrawal. 25 Of note, past studies on N/OFQ signalling have generated some contradictory results. 26 Activation of the NOPR with a selective agonist was reported to reduce alcohol drinking and seeking behavior, 27,28 while a selective NOPR antagonist, LY2940094, was reported to have the same effect.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release

Zhou

Stine

Prada

et al. 2023

Preprint

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Nociceptin/orphanin-FQ (N/OFQ) is a recently appreciated critical opioid peptide with key regulatory functions in several central behavioral processes including motivation, stress, feeding, and sleep. The functional relevance of N/OFQ action in the mammalian brain remains unclear due to a lack of high-resolution approaches to detect this neuropeptide with appropriate spatial and temporal resolution. Here we develop and characterize NOPLight, a genetically encoded sensor that sensitively reports changes in endogenous N/OFQ release. We characterized the affinity, pharmacological profile, spectral properties, kinetics, ligand selectivity, and potential interaction with intracellular signal transducers of NOPLight in vitro. Its functionality was established in acute brain slices by exogeneous N/OFQ application and chemogenetic induction of endogenous N/OFQ release from PNOC neurons. In vivo studies with fiber photometry enabled a direct recording of binding by N/OFQ receptor ligands, as well as the detection of natural or chemogenetically-evoked endogenous N/OFQ release within the paranigral ventral tegmental area (pnVTA). In summary, we show that NOPLight can be used to detect N/OFQ opioid peptide signal dynamics in tissue and freely-behaving animals.

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Conditioned Opioid Withdrawal Decreases Nociceptin/Orphanin FQ Levels in the Frontal Cortex and Olfactory Tubercle

Cited by 13 publications

References 30 publications

Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development

Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development

Sex differences in the Nociceptin/Orphanin FQ system in rat spinal cord following chronic morphine treatment

Development of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release

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