Biomedical subjects

G C Rossi

Publications and source records attributed to G C Rossi.

At least 19 recordsLinked to original sources

PubMed2006

The stress tensor of a molecular system: an exercise in statistical mechanics.

We prove that conservation of the stress tensor is a consequence of the invariance of the partition function under canonical diffeomorphisms. From this observation a simple and general derivation of the formula which gives the local expression of the stress tensor of a molecular system in terms of its microscopic degrees of freedom readily follows. The derivation is valid in the canonical as well as the microcanonical ensemble. It works both in the classical and in the quantum mechanical settings and for arbitrary boundary conditions. In particular, if periodic boundary conditions are assigned to the system, the usual minimal-image prescription is naturally born out for mathematical consistency. An interesting outcome of our general analysis is that only in the case of a short-range interaction potential a truly local formula for the stress tensor can exist.

Journal Article↗

PubMed2005

NPY-induced feeding: pharmacological characterization using selective opioid antagonists and antisense probes in rats.

The ability of neuropeptide Y to potently stimulate food intake is dependent in part upon the functioning of mu and kappa opioid receptors. The combined use of selective opioid antagonists directed against mu, delta or kappa receptors and antisense probes directed against specific exons of the MOR-1, DOR-1, KOR-1 and KOR-3/ORL-1 opioid receptor genes has been successful in characterizing the precise receptor subpopulations mediating feeding elicited by opioid peptides and agonists as well as homeostatic challenges. The present study examined the dose-dependent (5-80 nmol) cerebroventricular actions of general and selective mu, delta, and kappa1 opioid receptor antagonists together with antisense probes directed against each of the four exons of the MOR-1 opioid receptor gene and each of the three exons of the DOR-1, KOR-1, and KOR-3/ORL-1 opioid receptor genes upon feeding elicited by cerebroventricular NPY (0.47 nmol, 2 ug). NPY-induced feeding was dose-dependently decreased and sometimes eliminated following pretreatment with general, mu, delta, and kappa1 opioid receptor antagonists. Moreover, NPY-induced feeding was significantly and markedly reduced by antisense probes directed against exons 1, 2, and 3 of the MOR-1 gene, exons 1 and 2 of the DOR-1 gene, exons 1, 2, and 3 of the KOR-1 gene, and exon 3 of the KOR-3/ORL-1 gene. Thus, whereas the opioid peptides, beta-endorphin and dynorphin A(1-17) elicit feeding responses that are respectively more dependent upon mu and kappa opioid receptors and their genes, the opioid mediation of NPY-induced feeding appears to involve all three major opioid receptor subtypes in a manner similar to that observed for feeding responses following glucoprivation or lipoprivation.

Animals↗

PubMed2004

Opioid receptor involvement in food deprivation-induced feeding: evaluation of selective antagonist and antisense oligodeoxynucleotide probe effects in mice and rats.

Central administration of general and selective opioid receptor subtype antagonists in the rat has revealed a substantial role for mu, a moderate role for kappa, and a minimal role for delta receptors in the mediation of deprivation-induced feeding. Antisense probes directed against the kappa opioid receptor (KOP), nociceptin opioid receptor (NOP), and delta opioid receptor (DOP) genes in rats result in reductions similar to kappa and delta antagonists, whereas antisense probes directed against the mu opioid receptor (MOP) gene produced modest reductions relative to mu antagonists, suggesting that isoforms of the MOP gene may mediate deprivation-induced feeding. Since these isoforms were initially identified in mice, the present study compared the effects of general and selective opioid receptor antagonists on deprivation-induced feeding in rats and mice and antisense probes directed against exons of the MOP, DOP, KOP, and NOP genes on deprivation-induced feeding in the mouse. Food-deprived (12 and 24 h) rats and mice displayed similar profiles of reductions in deprivation-induced feeding following general, mu, and kappa opioid antagonists. In contrast, mice, but not rats, displayed reductions in deprivation-induced intake following delta antagonism as well as DOP antisense probes, suggesting a species-specific role for the delta receptor. Antisense probes directed against the KOP and NOP genes also reduced deprivation-induced intake in mice in a manner similar to kappa antagonism. However, the significant reductions in deprivation-induced feeding following antisense probes directed against either exons 2, 4, 7, 8, or 13 of the MOP gene were modest compared with mu antagonism, suggesting a role for multiple mu-mediated mechanisms.

Animals↗

PubMed2003

Feeding induced by food deprivation is differentially reduced by opioid receptor antisense oligodeoxynucleotide probes in rats.

The increases in food intake following 24 h of food deprivation are reduced by systemic and central administration of general opioid antagonists. The use of selective opioid antagonists revealed that mu-selective antagonists were more effective than kappa-selective antagonists in reducing deprivation-induced intake, whereas delta-selective antagonists were minimally effective. Antisense oligodeoxynucleotide (AS ODN) probes directed against different exons of the mu (MOP), delta (DOP), kappa (KOP) and nociceptin (NOP) opioid peptide receptor genes have been able to differentially alter feeding responses elicited by glucoprivation, lipoprivation and by different opioid peptides and receptor agonists. The present study examined whether lateral ventricular administration of AS ODN probes directed against different exons of the MOP, DOP, KOP or NOP opioid receptor genes altered food intake and body weight changes following 24 h of food deprivation in rats. Deprivation-induced feeding was significantly and maximally reduced by an AS ODN probe directed against exon 2, but not exons 1 or 3 of the KOP gene. This response was also significantly though modestly reduced by AS ODN probes directed against exons 2, 3 or 4 of the MOP gene, exon 1 of the DOP gene, or exon 1 of the NOP gene. Recovery of body weight following postdeprivation food reintroduction was significantly reduced by AS ODN probes directed against either exons 2, 3 or 4 of the MOP gene, exons 1 or 2 of the DOP gene, or exons 1, 2 or 3 of the KOP gene. The parallel patterns in the magnitude of alterations in deprivation-induced feeding by delta antagonists and DOP AS ODN probes on one hand, and by kappa antagonists and KOP AS ODN probes on the other, provide converging and complementary evidence for their relative involvement in this response. The modest reductions by MOP AS ODN probes relative to the more potent reductions induced by mu-selective antagonists suggest that the mu receptor-mediated actions upon deprivation-induced feeding may involve recently-identified splice variants or isoforms of the MOP gene.

Animals↗

PubMed2002

Anatomical and functional correlation of the endomorphins with mu opioid receptor splice variants.

The present study characterizes the relationship between the endogenous mu opioid peptides endomorphin-1 (EM-1) and endomorphin-2 (EM-2) and several splice variants of the cloned mu opioid receptor (MOR-1) encoded by the mu opioid receptor gene (Oprm). Confocal laser microscopy revealed that fibers containing EM-2-like immunoreactivity (-LI) were distributed in close apposition to fibers showing MOR-1-LI (exon 4-LI) and to MOR-1C-LI (exons 7/8/9-LI) in the superficial laminae of the lumbar spinal cord. We also observed colocalization of EM-2-LI and MOR-1-LI in a few fibers of lamina II, and colocalization of EM-2-LI and MOR-1C-LI in laminae I-II, and V-VI. To assess the functional relevance of the MOR-1 variants in endomorphin analgesia, we examined the effects of antisense treatments that targeted individual exons within the Oprm1 gene on EM-1 and EM-2 analgesia in the tail flick test. This antisense mapping study implied mu opioid receptor mechanisms for the endomorphins are distinct from those of morphine or morphine-6beta-glucuronide (M6G).

Alternative Splicing↗

PubMed2001

Analgesia elicited by OFQ/nociceptin and its fragments from the amygdala in rats.

The heptadecapeptide, orphanin FQ/nociceptin (OFQ/N), binds with high affinity to the ORL-1/KOR-3 opioid receptor clone, yet binds poorly with traditional opioid receptors. OFQ/N has a complex functional profile with relation to nociceptive processing, displaying pro-nociceptive properties in some studies, acting as an inhibitor of stress-induced analgesia in others, yet producing both spinal and supraspinal antinociceptive actions in other studies. Among the intracerebral sites at which OFQ/N might produce one or more of these actions is the amygdala which has been intimately implicated in both antinociceptive and stress-related responses. Therefore, the present study assessed whether microinjections into the amygdala of equimolar doses of OFQ/N(1-17) or its shorter-chained active fragments, OFQ/N(1-11) or OFQ/N(1-7), would produce analgesia as measured by either reactivity to high-intensity radiant heat or reactivity to electric shock, and produce hyperalgesia as measured by reactivity to lower-intensity radiant heat. OFQ/N(1-17) in the amygdala produced a dose-dependent and time-dependent increase in high-intensity tail-flick latencies with maximal effects observed at a dose range of 0.75-3 nmol, and lesser effects at lower (0.015-0.15 nmol) and higher (5.5-30 nmol) doses. Both OFQ/N(1-11) and OFQ/N(1-7) in the amygdala displayed lower magnitudes of analgesia than OFQ/N(1-17) on this measure, with OFQ/N(1-11) displaying maximal effects at higher (15-30 nmol) doses and OFQ/N(1-7) displaying maximal effects at lower (0.15-1.5 nmol) doses. In contrast to traditional mu and kappa opioids and beta-endorphin, none of the OFQ/N fragments in the amygdala exhibited any analgesic responses on the jump test. Finally, using a low-intensity radiant heat assay capable of detecting hyperalgesic responses, each of the OFQ/N fragments in the amygdala increased tail-flick latencies on this measure. Therefore, OFQ/N fragments appear to exert only analgesic responses in the amygdala with quantitative and qualitative differences relative to traditional opioid agonists.

Amygdala↗

PubMed2001

Carboxyl terminal peptides derived from prepro-orphanin FQ/nociceptin (ppOFQ/N) are produced in the hypothalamus and possess analgesic bioactivities.

Orphanin FQ/nociceptin (OFQ/N), the endogenous ligand for the ORL-1/KOR-3 receptor, produces a wide variety of behavioral responses. Its precursor protein, prepro-OFQ/N (ppOFQ/N) contains several series of amino acids bounded by pairs of basic amino acids, raising the possibility that additional functional neuropeptides could be generated by proteolytic posttranslational processing. Several of these processing products have been shown to have pharmacological activity, including the 17 amino acid peptide OFQ/N (mppOFQ/N(140-157)) which is a major product of this precursor in the hypothalamus. Here we have used a newly developed radioimmunoassay and RP-HPLC to detect mppOFQ/N(160-187) in mouse hypothalamic extracts. Murine ppOFQ/N(160-187) has potent analgesic activity supraspinally (3.4 nmol, i.c.v.) and spinally (4.3 nmol, i.t.). This analgesic activity was reversed by the opioid antagonist naloxone (5 mg/kg, s.c.) and kappa(1)-selective opioid antagonist nor-BNI (60 microg, i.c.v.), despite the inability of ppOFQ/N(160-187) to compete binding in mu, delta, kappa(1), kappa(3), or OFQ/N binding assays. These findings suggest that murine ppOFQ/N(160-187) may be a physiologically relevant neuropeptide with a novel mechanism of action.

Amino Acid Sequence↗

PubMed2001

Beta-endorphin-induced feeding: pharmacological characterization using selective opioid antagonists and antisense probes in rats.

Ventricular administration of the opioid beta END induces feeding in rats. Since its pharmacological characterization has not been fully identified, the present study examined whether equimolar doses of general and selective opioid antagonists as well as AS ODN opioid probes altered spontaneous daytime feeding over a 4-h time course elicited by beta END. beta END-induced feeding was significantly reduced by moderate (20--40-nmol, i.c.v.) doses of general (naltrexone) opioid antagonists, and lower (0.5--40-nmol) doses of selective mu (beta-funaltrexamine)-antagonists. Correspondingly, AS ODN probes directed against either exons 1, 3, or 4, but not exon 2, of the mu-opioid receptor clone reduced beta END-induced feeding; a missense ODN control probe was ineffective. The delta-antagonist Nti (20-40 nmol) reduced beta END-induced feeding to a lesser degree, and AS ODN probes targeting exon 1, but not 2 or 3, of the delta-opioid receptor clone significantly reduced beta END-induced feeding. Although the selective kappa(1)-receptor antagonist NBNI (20-40 nmol) significantly reduced beta END-induced feeding, this response was not altered by AS ODN probes directed against either exons 1, 2, or 3 of either the KOR-1 clone or the kappa(3)-like opioid receptor clone. These converging antagonist and AS ODN data firmly implicate the mu-opioid receptor in the mediation of beta END-induced feeding. The relative lack of convergence between the lesser effectiveness of Nti and NBNI in reducing beta END-induced feeding, and the lack of effectiveness of their corresponding AS ODN probes suggest that delta- and kappa-receptors play a minimal role in the mediation of this response.

Analgesics, Opioid↗

PubMed2001

[Lutzomyia longipalpis and Leishmaniasis visceral in Argentina].

Lutzomyia longipalpis is reported for the second time after 50 years in Misiones Province, Argentina. This insect is the vector of Leishmania (L.) chagasi, visceral leishmaniasis' parasite. The literature concerning the 16 visceral leishmaniasis cases in the country is reviewed. The cases were reported from Salta, Jujuy, Santiago del Estero and Chaco Provinces. Based on the clinical and entomo-epidemiological data two alternative hypotheses were evaluated: a) visceral leishmaniasis in Argentina is due to the visceralization of L. (V.) braziliensis or their variants, b) L (L.) chagasi remains in enzootic foci where the human contact is very unusual. Recommendations concerning the management of new cases have been made in order to confirm either one or both hypotheses. In consequence, the appropriate diagnosis and therapy could be arrived at according to the parasite actual identity, and the risk of outbreaks and mitigation measures could be estimated.

Adult↗

PubMed2000

Morphine and morphine-6beta-glucuronide-induced feeding are differentially reduced by G-protein alpha-subunit antisense probes in rats.

Although morphine and its active metabolite, morphine-6beta-glucuronide (M6G), each induce mu-opioid receptor-sensitive feeding, different antisense oligodeoxynucleotide (AS ODN) probes directed against the MOR-1 clone produce distinct effects. Thus, MOR-1 AS ODN probes directed against exons 1 or 4 reduce morphine-, but not M6G-induced feeding, whereas probes directed against exons 2 or 3 reduce M6G-, but not morphine-induced feeding. AS ODN probes directed against different G-protein alpha-subunits differentially reduced morphine (G(ialpha2)) and M6G (G(ialpha1))-induced analgesia. The present study evaluated the ability of AS ODN probes directed against G-protein alpha-subunits to reduce feeding induced by morphine and M6G in rats. The AS ODN probes (25 microg, i.c.v.) were administered once 24 h prior to morphine (5 microg, i.c.v.) or M6G (250 ng) and spontaneous free feeding was assessed 1, 2 and 4 h thereafter. In agreement with analgesic studies, morphine-induced feeding was significantly reduced by the G(ialpha2) AS ODN probe. Morphine-induced feeding was unaffected by AS ODN probes directed against either G(ialpha1), G(ialpha3), G(oalpha), G(x/zalpha), G(qalpha) or a nonsense control probe, and was significantly enhanced by pretreatment with the G(salpha) probe. In contrast, M6G-induced feeding was significantly reduced by AS ODN probes directed against either G(ialpha1), G(ialpha3) or G(x/zalpha), whereas AS ODN probes targeting G(ialpha2), G(oalpha), G(salpha), G(qalpha) or a nonsense control probe were ineffective. When M6G-induced feeding was assessed at a dose (500 ng) which was sensitive to MOR-1 AS ODN effects, none of the G-protein alpha-subunit AS ODN probes were effective. These data indicate that morphine and M6G-induced feeding are mediated through different G-protein alpha-subunits, and provide further evidence for separate and distinct molecular mechanisms mediating these functional responses through different opioid receptors. This strongly suggests that M6G may act through a novel opioid receptor displaying a distinct pharmacological mechanism.

Animals↗

PubMed2000

Autoradiographic localization of (125)I[Tyr(14)]orphanin FQ/nociceptin and (125)I[Tyr(10)]orphanin FQ/nociceptin(1-11) binding sites in rat brain.

The endogenous ligand for the orphan opioid receptor, orphanin FQ/nociceptin (OFQ), has recently been characterized. The OFQ peptide sequence contains paired basic amino acids, suggesting the possibility of posttranslational processing to a peptide containing the first 11 amino acids of the OFQ peptide. This peptide has been reported in the brain and it has a unique pharmacology. In the present study, we compared the autoradiographic distribution of (125)I[Tyr(14)]OFQ and (125)I[Tyr(10)]OFQ(1-11) in coronal rat brain sections. Nonspecific binding was defined with unlabeled OFQ or OFQ(1-11), respectively. Both radioligands demonstrated high levels of specific binding (>95% of total binding), with no appreciable binding in white matter areas with either ligand. (125)I[Tyr(14)]OFQ binding was widely distributed throughout the rat brain. In contrast, (125)I[Tyr(10)]OFQ(1-11) binding was more restricted. The highest (125)I[Tyr(14)]OFQ binding levels measured in this study were found in the locus coeruleus, an area which contained very low (125)I[Tyr(10)]OFQ(1-11) binding. Both ligands labeled the cortex, hippocampus and amygdala. In the thalamus, (125)I[Tyr(14)]OFQ binding was prominent in most nuclei, whereas (125)I[Tyr(10)]OFQ(1-11) binding was restricted to the midline thalamus. (125)I[Tyr(14)]OFQ binding was heavy in the suprachiasmatic hypothalamus, and moderate in other hypothalamic nuclei. (125)I[Tyr(10)]OFQ(1-11) binding in the hypothalamus, however, was present mainly in the ventromedial hypothalamic nucleus. Lower binding levels of both ligands were found in the caudate putamen. The distinct autoradiographic patterns of these two ligands are consistent with different binding sites, which might help explain their different functional activities.

Animals↗

PubMed2000

Mercaptoacetate induces feeding through central opioid-mediated mechanisms in rats.

The endogenous opioid system has been implicated in the mediation of food intake elicited by such regulatory challenges as glucoprivation induced by 2-deoxy-D-glucose (2DG) or food deprivation in rodents. Administration of the free fatty acid oxidation inhibitor, mercaptoacetate (MA), produces a potent short-term increase in feeding in rats, the mechanisms of which have been dissociated from that elicited by 2DG. The present study evaluated whether MA-induced feeding in rats was mediated by the endogenous opioid system through systemic administration of the general opioid antagonist, naltrexone, through central administration of either general, mu, mu(1), kappa(1) or delta opioid antagonists, and through central administration of antisense oligodeoxynucleotide (AS ODN) probes directed against specific exons of either the mu (MOR-1), kappa (KOR-1), kappa(3) (KOR-3/ORL-1) or delta (DOR-1) opioid receptor clones. MA-induced feeding was significantly and dose-dependently reduced by systemic naltrexone (0.005-5 mg/kg); these ingestive effects were quite selective since neither total, ambulatory nor stereotypic activity was affected by either MA itself or MA paired with naltrexone. MA-induced feeding was significantly reduced by central pretreatment with either naltrexone (0.1-20 microgram) or mu-selective (beta-funaltrexamine, 0.1-20 microgram), mu(1)-selective (naloxonazine, 1-20 microgram), kappa(1)-selective (nor-binaltorphamine, 0.1-20 microgram), or delta-selective (naltrindole, 1-20 microgram) opioid receptor antagonists. MA-induced feeding was significantly reduced by AS ODN probes directed against either exons 1, 2 or 3, but not exon 4 of the MOR-1 clone, exon 3, but not exons 1 or 2 of the KOR-1 clone, exons 1 or 2, but not exon 3 of the KOR-3/ORL-1 clone, and exon 1, but not exons 2 or 3 of the DOR-1 clone. These data are discussed in terms of opioid mediation of ingestive responses related to fat, and in terms of potential central sites of action at which lipoprivic ingestive responses might act.

Animals↗

PubMed1999

Antisense mapping KOR-1: evidence for multiple kappa analgesic mechanisms.

In binding assays, both dynorphin B and alpha-neoendorphin are relatively selective for the kappa1b site, unlike U50,488H which has high affinity for both kappa1a and kappa1b sites. In vivo, U50,488H, dynorphin B and alpha-neoendorphin analgesia are reversed by the kappa1-selective antagonist, nor-binaltorphimine (norBNI). Antisense mapping the three exons of KOR-1 revealed that probes targeting all three exons blocked U50,488H analgesia, as expected. However, the selectivity profile of dynorphin B and alpha-neoendorphin analgesia towards the various antisense oligodeoxynucleotides differed markedly from U50,488H, implying a different receptor mechanism of action.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1999

First record of Aedes albopictus (Skuse) from Argentina.

Aedes albopictus was collected in San Antonio City, Misiones Province, Argentina, near the border with Brazil in March, 1998. Collected material included 12 pupae, 1 recently emerged adult female, and a few larvae, which were found in a dish, a plough disk, and a tin pot. From the collected pupae, 5 males and 4 females emerged in the laboratory.

Aedes↗

PubMed1998

Potency ratios of morphine and morphine-6beta-glucuronide analgesia elicited from the periaqueductal gray, locus coeruleus or rostral ventromedial medulla of rats.

The present study examined whether morphine and morphine-6beta-glucuronide (M6G) analgesia on the tail-flick and jump tests differed in potency in the periaqueductal gray, the locus coeruleus or the rostral ventromedial medulla. Morphine and M6G significantly and dose-dependently elicited analgesia on both nociceptive tests from each site. Site-specific differences were observed in the potency of M6G, but not morphine analgesia on both tests. Periaqueductal gray placements displayed analgesic ED50s on the tail-flick (morphine: 2.1 microgram, M6G: 0.2 microgram) and jump (morphine: 2.2 microgram, M6G: 0.4 microgram) tests with respective potency ratios of 12.9 and 6.5. Locus coeruleus placements displayed analgesic ED50s on the tail-flick (morphine: 1.7 microgram, M6G: 0.1 microgram) and jump (morphine: 3.4 microgram, M6G: 0.2 microgram) tests with respective potency ratios of 15.9 and 15.1. Rostral ventromedial placements displayed analgesic ED50s on the tail-flick (morphine: 1.4 microgram, M6G: 0.06 microgram) and jump (morphine: 1.9 microgram M6G: 0.08 microgram) tests with potency ratios of 21.9 on both tests. The greater analgesic sensitivity of the rostral ventromedial medulla to M6G may be due to either pharmacodynamic (splice variants of the MOR-1 gene) and/or pharmacokinetic (lipid solubility) factors.

Analgesics, Opioid↗

PubMed1998

Methadone analgesia in morphine-insensitive CXBK mice.

Methadone, a potent opioid analgesic, has long been considered a mu-opioid, based upon the similarities between its actions and those of morphine. This classification is supported by the sensitivity of methadone analgesia to the highly mu-opioid receptor-selective antagonist beta-funaltrexamine. Yet, CXBK mice respond normally to methadone despite their insensitivity to systemic morphine, distinguishing between the receptor mechanisms of the two drugs. Beta-funaltrexamine antagonizes methadone analgesia in CXBK mice, implying that the opioid is still acting through a mu-opioid receptor. These results reveal distinct analgesic mechanisms for morphine and methadone and provide further support for multiple subtypes of mu-opioid receptors.

Analgesia↗

PubMed1998

Antisense mapping of opioid receptor clones: effects upon 2-deoxy-D-glucose-induced hyperphagia.

Antisense oligodeoxynucleotides (AS ODNs) directed against exons 1 and 2 of the MOR-1 clone significantly and markedly reduced (81-93%) hyperphagia induced by the anti-metabolic glucose analogue, 2-deoxy-d-glucose (2DG) across a 4 h time course. AS ODNs directed against exons 3 or 4 of the MOR-1 clone had a more limited (1-2 h) duration of action upon 2DG-induced hyperphagia. 2DG-induced hyperphagia was significantly reduced by AS ODNs directed against exon 2 (44-51%), but not exons 1 or 3 of the KOR-1 clone across a 4 h time course. Whereas an AS ODN probe directed against the KOR3/ORL-1 clone produced small (36%), but significant reductions in 2DG-induced hyperphagia, an AS ODN probe directed against the DOR-1 clone was ineffective. These data provide further converging evidence for the roles of primarily mu, but also kappa1 and kappa3 opioid receptors in mediating the hyperphagic effects of glucoprivation.

Animals↗

PubMed1998

Orphan opioid receptor antisense probes block orphanin FQ-induced hyperphagia.

Orphanin FQ/nociceptin binds with high affinity to the orphan opioid receptor-like/K-3 (ORL1/KOR-3) clone, and stimulates feeding. The present study demonstrated that antisense oligodeoxynucleotides directed against either exons 1, 2 or 3 of the ORL1/KOR-3 clone reduced orphanin FQ/nociceptin-induced hyperphagia. A missense probe was ineffective. Naltrexone dose-dependently reduced orphanin FQ/nociceptin-induced hyperphagia. These data suggest that the receptor responsible for orphanin FQ/nociceptin-induced hyperphagia is encoded by the ORL1/KOR-3 clone.

Animals↗