Pharmacological and molecular characterization of endogenous opioid peptide-induced feeding responses in rats.
Item
-
Title
-
Pharmacological and molecular characterization of endogenous opioid peptide-induced feeding responses in rats.
-
Identifier
-
AAI3037446
-
identifier
-
3037446
-
Creator
-
Silva, Robert Michael.
-
Contributor
-
Adviser: Richard Bodnar
-
Date
-
2002
-
Language
-
English
-
Publisher
-
City University of New York.
-
Subject
-
Biology, Neuroscience | Health Sciences, Pharmacology | Psychology, Experimental | Psychology, Behavioral
-
Abstract
-
Central administration of the endogenous opioid peptides, beta-endorphin and dynorphin potently stimulates ingestive behaviors. A series of four studies were conducted to elucidate the pharmacological mechanisms mediating these ingestive effects. The results of the first study demonstrated that beta-endorphin-induced feeding was significantly attenuated by pretreatment with either general (NTX), mu (betaFNA), delta (naltrindole) or kappa1 (NorBNI) opioid receptor antagonists. In addition, beta-endorphin-induced feeding was significantly reduced following pretreatment with antisense targeting either exons 1, 3, or 4 of the MOR-1 gene, and exon1 of the DOR-1 gene. In contrast, antisense directed against any exons of either the KOR-1 or KOR-3/ORL-1 clones were ineffective, thereby suggesting that the primary opioid receptor mediating beta-endorphin-induced feeding is the mu opioid receptor. Using a similar technique, the second study revealed that dynorphin-induced intake was also significantly reduced by pretreatment with either general-, kappa1-, delta- and mu-opioid antagonists. In contrast to beta-endorphin-induced feeding, dynorphin-induced feeding was significantly reduced by antisense targeting either exons 1 and 2, but not 3 of the KOR-1 gene, exons 1 and 2, but not 3 of the KOR-3/ORL-1 gene, exon1, but not 2 or 3 of the DOR-1 gene, and exon1, but not 2, 3 or 4 of the MOR-1 gene, thereby suggesting that dynorphin-induced feeding is mediated primarily by the kappa1 opioid receptor. The results from the third study revealed that feeding elicited by morphine and its active metabolite, morphine-6beta-glucuronide (M6G) can be distinguished from each other using antisense targeting individual G-protein receptor subunits. Antisense targeting only the Gialpha2 subunit significantly reduced morphine-induced feeding whereas antisense targeting either the G ialpha1, Gialpha3, or Gx/z alpha subunits significantly reduced M6G-induced feeding. The final study revealed that feeding elicited by beta-endorphin and dynorphin were both significantly reduced by pretreatment with antisense targeting the G ialpha1 subunit. In addition, dynorphin-induced feeding was also significantly reduced by pretreatment with antisense targeting the Goalpha subunit. The common sensitivity beta-endorphin and dynorphin-induced feeding suggests that this neuronal network may represent a final common pathway for a distinct class of opioid agonists.
-
Type
-
dissertation
-
Source
-
PQT Legacy CUNY.xlsx
-
degree
-
Ph.D.
