Department of Psychology

Molecular Opioid Manipulations and Ingestive Behavior

The pharmacological, biochemical and behavioral characterization of endogenous opioid receptor subtypes was followed by the identification and cloning of the major opioid receptor genes, mu (MOP), kappa (KOP) and delta (DOP), as well as the identification of the orphan opioid receptor (NOP). These findings led to the development of two major molecular techniques to study the role of these genes in behavioral processes: a) the knockout approach wherein a particular gene is deleted in development and the consequences studied, and b) the knockdown approach in which portions of a particular gene are temporarily inactivated. In a long-term collaboration with Drs. Gavril Pasternak, YX Pan and Grace Rossi, our laboratory has been able to administer central employ antisense oligodeoxynucleotides (AS ODN) probes developed as 15-22 cDNA nucleotide bases to inactivate mRNA sequences of particular exons of the MOP, KOP, DOP and NOP opioid receptor genes. Our studies examined the molecular pharmacology of feeding elicited by opioid peptides (dynorphin, beta-endorphin), opioid receptor agonists (morphine, DAMGO, morphine-6B-glucuronide) and environmental situations (ad libitum feeding and body weight, food deprivation, glucoprivation, lipoprivation).

Opioid Antisense Publications of the Bodnar Laboratory:

Rossi GC and Bodnar, RJ. Interactive mechanisms of supraspinal sites of opioid analgesic action. Special Issue on Understanding opioid actions, pain and analgesia: a tribute to Dr. Gavril Pasternak. Cellular and Molec Neurobiol, in press, 2020. (https://doi.org/10.1007/s10571-020-00961-9).

Israel, Y, Y Kandov, A Kest, SR Lewis and RJ Bodnar. Neuropeptide Y-induced feeding: pharmacological characterization using selective opioid antagonists and antisense probes in rats. Peptides 26: 1167-1175, 2005.

Hadjimarkou, MM, A Singh, Y Kandov, Y Israel, Y-X Pan, GC Rossi, GW Pasternak and RJ Bodnar. Opioid receptor involvement in food deprivation-induced feeding: evaluation of selective antagonist and antisense oligodeoxynucleotides probe effects in mice and rats. J. Pharmacol. Exp. Ther. 311: 1188-1202, 2004.

Hadjimarkou, MM, E Khaimova, Y-X Pan, GC Rossi, GW Pasternak and RJ Bodnar. Feeding induced by food deprivation is differentially reduced by opioid receptor antisense oligodeoxynucleotide probes in rats. Brain Res. 987: 223-232.

Silva, RM and RJ Bodnar. Antisense oligodeoxynucleotide technology as an effective tool in elucidating neuropeptide orexigenic mechanisms. Curr. Topics in Peptide and Protein Res. 5: 1-19, 2003.

Hadjimarkou, MM, RM Silva, GC Rossi, GW Pasternak and RJ Bodnar. Feeding induced by food deprivation is differentially reduced by G-protein alpha-subunit antisense probes in rats. Brain Res. 955: 45-54, 2002.

Silva, RM, HC Grossman, GC Rossi, GW Pasternak and RJ Bodnar. Pharmacological characterization of beta-endorphin and dynorphin A(1-17)-induced feeding using G-protein alpha-subunit antisense probes in rats. Peptides 23:1101-1106, 2002.

Silva, RM, HC Grossman, MM Hadjimarkou, GC Rossi, GW Pasternak and RJ Bodnar. Dynorphin A(1-17)-induced feeding: pharmacological characterization using selective opioid antagonists and antisense probes in rats. J. Pharmacol. Exp. Ther. 301: 513-518, 2002.

Silva, RM, MM Hadjimarkou, GC Rossi, GW Pasternak and RJ Bodnar. B-endorphin-induced feeding: pharmacological characterization using selective opioid antagonists and antisense probes in rats. J. Pharmacol. Exp. Ther. 297: 590-596, 2001.

Ragnauth, A, A Schuller, M Morgan, J Chan, S Ogawa, J Pintar, RJ Bodnar and DW Pfaff. Female preproenkephalin knockout mice display altered emotional responses. Proc. Natl. Acad. Sci. (USA) 98: 1958-1963, 2001.

Silva, RM, GC Rossi, JP Mathis, KM Standifer, GW Pasternak and RJ Bodnar. Morphine and morphine-6B-glucuronide-induced feeding are differentially reduced by G-protein alpha-subunit antisense probes in rats. Brain Res. 876: 62-75, 2000.

Letchworth, SR, JP Mathis, GC Rossi, RJ Bodnar and GW Pasternak. Autoradiographic localization of 125I[Tyr14]Orphanin FQ/Nociceptin and 125I[Tyr10]Orphanin FQ/Nociceptin1-11 binding sites in rat brain. J. Comp. Neurol. 423: 319-329, 2000.

Stein, JA, V Znamensky, F Baumer, GC Rossi, GW Pasternak and RJ Bodnar. Mercaptoacetate induces feeding through central opioid-mediated mechanisms in rats. Brain Res. 864: 240-251, 2000.

Leventhal, L, R. Silva, GC Rossi, GW Pasternak and RJ Bodnar. Morphine-6ß-glucuronide-induced hyperphagia: characterization of opioid action by selective antagonists and antisense mapping in rats. J. Pharmacol. Exp. Ther 287: 538-544, 1998.

Leventhal, L, Mathis, JP, Rossi, GC, Pasternak, GW and Bodnar, RJ. Orphan opioid receptor antisense probes block orphanin FQ/nociceptin-induced hyperphagia. Eur. J. Pharmacol. 349: R1-R3, 1998.

Burdick, K, W-Z Yu, A Ragnauth, M Moroz, YX Pan, GC Rossi, GW Pasternak and RJ Bodnar. Antisense mapping of opioid receptor clones: effects upon 2-deoxy-D-glucose-induced hyperphagia. Brain Res. 794: 359-363, 1998.

Leventhal, L, LB Stevens, GC Rossi, GW Pasternak and RJ Bodnar. Antisense mapping of the MOR-1 opioid receptor clone: modulation of hyperphagia induced by [D-Ala2, MePhe4, Gly-ol5]-enkephalin (DAMGO). J. Pharmacol. Exp Ther. 282: 1402-1407, 1997.

Rossi, GC, L Leventhal, Y-X Pan, J Cole, W Su, RJ Bodnar and GW Pasternak. Antisense mapping MOR-1 in the rat: Distinguishing between morphine and morphine-6-beta-glucuronide antinociception. J. Pharmacol. Exp. Ther. 281: 109-114, 1997.

Leventhal, L, JL Cole, GC Rossi, YX Pan, GW Pasternak and RJ Bodnar. Antisense oligodeoxynucleotides against the MOR-1 clone alter weight and ingestive responses in rats. Brain Res. 719: 78-84, 1996.