Biomedical subjects

Grace C Rossi

Publications and source records attributed to Grace C Rossi.

6 recordsLinked to original sources

PubMed2006

Codeine and 6-acetylcodeine analgesia in mice.

1. Acetylation of morphine at the 6-position changes its pharmacology. To see if similar changes are seen with codeine, we examined the analgesic actions of codeine and 6-acetylcodeine. 2. Like codeine, 6-acetylcodeine is an effective analgesic systemically, supraspinally and spinally, with a potency approximately a third that of codeine. 3. The sensitivity of 6-acetylcodeine analgesia to the mu-selective antagonists beta-FNA and naloxonazine confirmed its classification as a mu opioid. However, it differed from the other mu analgesics in other paradigms. 4. Antisense mapping revealed the sensitivity of 6-acetylcodeine to probes targeting exons 1 and 2 of the mu opioid receptor gene (Oprm), a profile distinct from either codeine or morphine. Although heroin analgesia also is sensitive to antisense targeting exons 1 and 2, heroin analgesia also is sensitive to the antagonist 3-O-methylnaltrexone, while 6-acetylcodeine analgesia is not. 5. Thus, 6-acetylcodeine is an effective mu opioid analgesic with a distinct pharmacological profile.

Analgesia↗

PubMed2003

Reciprocal interactions between the amygdala and ventrolateral periaqueductal gray in mediating of Q/N(1-17)-induced analgesia in the rat.

The opioid peptide, Orphanin FQ/nociceptin (OFQ/N(1-17))(,) its active fragments, and a related precursor peptide each produce analgesia following microinjection into the amygdala of rats. OFQ/N(1-17)-induced analgesia elicited from the amygdala is blocked by amygdala pretreatment of either general, mu, kappa, or delta-opioid antagonists even though OFQ/N(1-17) binds poorly to these receptor subtypes, and the antagonists bind poorly to the ORL-1/KOR-3 receptor. Agonists at mu and kappa opioid receptors as well as beta-endorphin each produce analgesia elicited from the amygdala that is blocked by opioid antagonist pretreatment in the ventrolateral periaqueductal gray (vlPAG) of rats. The present study examined whether pretreatment of general and selective opioid antagonists in the vlPAG blocked OFQ/N(1-17)-induced analgesia on the tail-flick test elicited from the amygdala, and whether pretreatment of general and selective opioid antagonists in the amygdala blocked OFQ/N(1-17)-induced analgesia elicited from the vlPAG of rats. OFQ/N(1-17)-induced analgesia elicited from the amygdala was significantly and markedly reduced following vlPAG pretreatment with a dose range of either naltrexone, beta-funaltrexamine (beta-FNA, mu), nor-binaltorphamine (NBNI, kappa) or naltrindole (NTI, delta). In contrast, opioid antagonists administered into misplaced mesencephalic control placements ventral and lateral to the vlPAG actually enhanced OFQ/N(1-17)-induced analgesia elicited from the amygdala. OFQ/N(1-17)-induced analgesia elicited from the vlPAG was significantly and markedly reduced following amygdala pretreatment with naltrexone and NBNI, to a lesser degree by NTI, and was unaffected by beta-FNA. Yet, opioid antagonists administered into misplaced amygdala control placements were generally ineffective in altering OFQ/N(1-17)-induced analgesia elicited from the vlPAG. Latencies were transiently increased by general, but not selective opioid antagonist treatment alone in the amygdala, but not the vlPAG. These data indicate reciprocal and regional interactions between the amygdala and vlPAG in the mediation of OFQ/N(1-17) by classic opioid receptor subtype antagonists in rats.

Amygdala↗

PubMed2002

Feeding induced by food deprivation is differentially reduced by G-protein alpha-subunit antisense probes in rats.

Antisense oligodeoxynucleotide (AS ODN) probes directed against the alpha-subunit of different G-proteins have been used to differentiate feeding responses in rats elicited by different opioid agonists, including morphine, beta-endorphin and dynorphin. Furthermore, antisense probes directed against G(o)alpha, but not G(s)alpha, G(q)alpha or G(i)alpha, significantly reduced nocturnal feeding in rats. The present study examined whether food intake and weight changes elicited by 24 h of food deprivation were significantly altered by ventricular administration of antisense probes directed against either G(i)alpha(1), G(i)alpha(2), G(i)alpha(3), G(s)alpha, G(o)alpha, G(q)alpha or G(x/z)alpha as well as a control nonsense probe in rats. Deprivation-induced weight loss was significantly enhanced by antisense probes directed against G(s)alpha and G(x/z)alpha, whereas weight recovery 24 h following reintroduction of food was significantly reduced by antisense probes directed against G(i)alpha(2), G(q)alpha and G(o)alpha. Selective antisense probe effects were noted for deprivation-induced intake with G(s)alpha and G(q)alpha probes exerting the greatest reductions, G(x/z)alpha, G(i)alpha(2), and G(i)alpha(3) probes exerting lesser effects, and G(i)alpha(1) and G(o)alpha probes failing to affect deprivation-induced intake. Importantly, the nonsense control probe failed to alter deprivation-induced intake or weight. The reductions in deprivation-induced intake by AS ODN probes directed against G(s)alpha or G(q)alpha were not accompanied by any evidence of a conditioned taste aversion. These data indicate important distinctions between G-protein mediation of different effector signaling pathways mediating feeding responses elicited under natural (e.g. nocturnal feeding) and regulatory challenge (e.g. food deprivation) conditions.

Animals↗

PubMed2002

Pharmacological characterization of beta-endorphin- and dynorphin A(1-17)-induced feeding using G-protein alpha-subunit antisense probes in rats.

Antisense (AS) oligodeoxynucleotides targeting G-protein alpha-subunits distinguish feeding responses of morphine and its metabolite, as well as nocturnal and deprivation-induced feeding. The present study examined whether feeding elicited by beta-endorphin (betaEND) or dynorphin A(1-17) was altered by ventricularly-applied G(i)alpha(1), G(i)alpha(2), G(i)alpha(3), G(s)alpha, G(o)alpha, G(q)alpha or G(x/z)alpha AS probes, or a nonsense (NS) control. The betaEND-induced feeding was reduced by the G(i)alpha(1) and G(x/z)alpha AS probes, and increased by G(i)alpha(2) or G(i)alpha(3) AS treatment. Dynorphin-induced feeding was attenuated by G(i)alpha(1) and G(o)alpha AS treatment. Yet, G(s)alpha or G(q)alpha AS and NS treatments failed to alter opioid agonist-induced feeding. These data provide initial characterization of potential effector signaling pathways mediating betaEND and dynorphin-induced feeding.

Animals↗

PubMed2002

Characterization of rat prepro-orphanin FQ/nociceptin((154-181)): nociceptive processing in supraspinal sites.

Orphanin FQ/nociceptin (OFQ/N), the endogenous ligand for the orphan receptor-like/kappa(3)-like opioid receptor clone, produces a variety of behavioral responses, including those associated with pronociception and antinociception. The OFQ/N precursor rattus-proOFQ (rppOFQ/N) contains several paired basic amino acids, which raises the possibility that post-translational processing can be responsible for the production of a number of additional biologically active peptide fragments. One of these putative peptides, rppOFQ/N (rppOFQ/N(154-181)), was examined for antinociceptive and pronociceptive processes in four brain sites involved in pain inhibition: the ventrolateral periaqueductal gray (vlPAG), the amygdala, the locus coeruleus (LC), and the rostroventromedial medulla (RVM). Endogenous rppOFQ/N(154-181) was identified in each region. rppOFQ/N(154-181) produced a dose-dependent antinociception in all four sites using the tailflick assay. Injections into misplaced cannula sites failed to exert effects. Antinociception in the four sites differed in their response to the opioid antagonist naloxone. Naloxone pretreatment completely blocked rppOFQ/N(154-181)-induced antinociception in the vlPAG and the amygdala, but not in the LC or RVM. In contrast rppOFQ/N(154-181) was hyperalgesic in the LC and RVM, but not in the vlPAG or amygdala. rppOFQ/N(154-181) also was compared with either its N-terminal 17-amino acid peptide (rppOFQ/N(154-170), also known as OFQ2) or its 8-amino acid C-terminal fragment (rppOFQ/N(174-181)). Although both rppOFQ/N(154-181) and rppOFQ/N(154-170) produced antinociception, the latter was less effective because the C-terminal fragment was inactive. Thus, rppOFQ/N(154-181) has complex antinociceptive and pronociceptive actions within the brain, and the pharmacological specificity of its actions differs among supraspinal sites.

Amygdala↗

PubMed2002

Dynorphin A(1-17)-induced feeding: pharmacological characterization using selective opioid antagonists and antisense probes in rats.

Ventricular administration of the opioid dynorphin A(1-17) induces feeding in rats. Because its pharmacological characterization has not been fully identified, the present study examined whether a dose-response range of general and selective opioid antagonists as well as antisense oligodeoxynucleotide (AS ODN) opioid probes altered daytime feeding over a 4-h time course elicited by dynorphin. Dynorphin-induced feeding was significantly reduced by a wide range of doses (5-80 nmol i.c.v.) of the selective kappa(1)-opioid antagonist nor-binaltorphamine. Correspondingly, AS ODN probes directed against either exons 1 and 2, but not 3 of the kappa-opioid receptor clone (KOR-1) reduced dynorphin-induced feeding, whereas a missense oligodeoxynucleotide control probe was ineffective. Furthermore, AS ODN probes directed against either exons 1 or 2, but not 3 of the kappa(3)-like opioid receptor clone (KOR-3/ORL-1) also attenuated dynorphin-induced feeding. Although the selective mu-antagonist beta-funaltrexamine (20-80 nmol) reduced dynorphin-induced feeding, an AS ODN probe directed only against exon 1 of the mu-opioid receptor clone was transiently effective. Neither general (naltrexone, 80 nmol) nor delta (naltrindole, 80 nmol)-selective opioid antagonists were particularly effective in reducing dynorphin-induced feeding, and an AS ODN probe targeting the individual exons of the delta-opioid receptor clone failed to significantly reduce dynorphin-induced feeding. These converging antagonist and AS ODN data firmly implicate the kappa(1)-opioid receptor and the KOR-1 and KOR-3/ORL-1 opioid receptor genes in the mediation of dynorphin-induced feeding.

Animals↗