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Titolo:
DIFFERENTIAL DESENSITIZATION OF MU-OPIOID AND DELTA-OPIOID RECEPTORS IN SELECTED NEURAL PATHWAYS FOLLOWING CHRONIC MORPHINE TREATMENT
Autore:
NOBLE F; COX BM;
Indirizzi:
UNIFORMED SERV UNIV HLTH SCI,DEPT PHARMACOL,4301 JONES BRIDGE RD BETHESDA MD 20814 UNIFORMED SERV UNIV HLTH SCI,DEPT PHARMACOL BETHESDA MD 20814
Titolo Testata:
British Journal of Pharmacology
fascicolo: 1, volume: 117, anno: 1996,
pagine: 161 - 169
SICI:
0007-1188(1996)117:1<161:DDOMAD>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
VENTRAL TEGMENTAL AREA; RAT LOCUS COERULEUS; ADENYLATE-CYCLASE; NUCLEUS-ACCUMBENS; OPIATE WITHDRAWAL; PERIAQUEDUCTAL GRAY; CHRONIC EXPOSURE; CROSS-TOLERANCE; ASSAY METHOD; SPINAL-CORD;
Keywords:
CAUDATE-PUTAMEN; NUCLEUS ACCUMBENS; THALAMUS; PERIAQUEDUCTAL GRAY; OPIOID RECEPTORS; DESENSITIZATION; MORPHINE; CHRONIC TREATMENT; ADENYLYL CYCLASE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
54
Recensione:
Indirizzi per estratti:
Citazione:
F. Noble e B.M. Cox, "DIFFERENTIAL DESENSITIZATION OF MU-OPIOID AND DELTA-OPIOID RECEPTORS IN SELECTED NEURAL PATHWAYS FOLLOWING CHRONIC MORPHINE TREATMENT", British Journal of Pharmacology, 117(1), 1996, pp. 161-169

Abstract

1 Morphine produces a plethora of pharmacological effects and its chronic administration induces several side-effects. The cellular mechanisms by which opiates induce these side-effects are not fully understood. Several studies suggest that regulation of adenylyl cyclase activity by opioids and other transmitters plays an important role in the control of neural function. 2 The aim of this study was to evaluate desensitization of mu- and delta-opioid receptors, defined as a reduced ability of opioid agonists to inhibit adenylyl cyclase activity, in four different brain structures known to be involved in opiate drug actions: caudate putamen, nucleus accumbens, thalamus and periaqueductal gray(PAG). Opiate regulation of adenylyl cyclase in these regions has been studied in control and morphine-dependent rats. 3 The chronic morphine treatment used in the present study (subcutaneous administration of15.4 mg morphine/rat/day for 6 days via osmotic pump) induced significant physical dependence as indicated by naloxone-precipitated withdrawal symptoms. 4 Basal adenylyl cyclase in the four brain regions was not modified by this chronic morphine treatment. In the FAG and the thalamus, a desensitization of mu- and delta-opioid receptors was observed, characterized by a reduced ability of Tyr-D-Ala-Gly-(NMe)Phe-Gly-ol(DAMGO; mu), Tyr-D-Pen-Gly-Phe-D-Pen (DPDPE; delta) and [D-Ala(2)]-deltorphin-II (DT-II; delta) to inhibit adenylyl cyclase, activity following chronic morphine treatment. 5 The opioid receptor desensitizationin FAG and thalamus appeared to be heterologous since the metabotropic glutamate receptor agonists, L-AP4 and glutamate, and the 5-hydroxytryptamine (5-HT)(1A) receptor agonist, R(+)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), also showed reduced inhibition of adenylyl cyclase activity following chronic morphine treatment. 6 In the nucleus accumbens and the caudate putamen, desensitization of delta-opioid receptor-mediated inhibition without modification of mu-opioid receptor-mediated inhibition was observed. An indirect mechanism probably involving dopaminergic systems is proposed to explain the desensitization of delta-mediated responses and the lack of mu-opioid receptor desensitization after chronic morphine treatment in caudate putamen and nucleus accumbens. 7 These results suggest that adaptive responses occurring during chronic morphine administration are not identicalin all opiate-sensitive neural populations.

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Documento generato il 02/04/20 alle ore 11:31:42