title: The nociceptin orphanin FQ peptide receptor agonist, Ro64-6198, impairs recognition memory formation through interaction with glutamatergic but not cholinergic receptor antagonists.
abstract: We previously reported that the selective nociceptin orphanin peptide (NOP) receptor agonist, Ro64-6198, impairs mnemonic function through glutamatergic-dependent mechanisms. The aim of the current study was to determine whether the amnesic effects of Ro64-6198 involve a cholinergic component. The effects of systemic administration of Ro64-6198 (0.3 and 1 mg/kg, i.p.), the cholinergic nicotinic receptor antagonist, mecamylamine (0.1 and 1 mg/kg, s.c.), the cholinergic muscarinic receptor antagonist, scopolamine (0.1 and 0.3 mg/kg, s.c.), and the glutamatergic NMDA receptor antagonist, MK-801 (0.03 and 0.1 mg/kg, s.c.), were studied in the mouse object recognition task. All compounds tested were effective in disrupting formation of long-term (24-h delay) recognition memory. Drug interaction studies were then conducted to reveal the existence of functional interactions between NOP receptors and cholinergic and/or NMDA receptors. Co-administration of silent doses of Ro64-6198 (0.3 mg/kg) and MK-801 (0.01 mg/kg) produced clear-cut memory impairment. Similar synergistic effects were observed with the combination of mecamylamine (0.03 mg/kg) and scopolamine (0.1 mg/kg). In contrast, co-administration of Ro64-6198 (0.3 mg/kg) with either mecamylamine (0.03 and 0.1 mg/kg) or scopolamine (0.1 mg/kg) was without any effect on recognition memory. These findings suggest that NOP receptor may modulate memory formation through a functional interaction with glutamatergic but not cholinergic receptors.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Département de Médecine Transrationnelle et Neurogénétique, Illkirch, France.
authors.forename: David
authors.initials: D
authors.lastname: Reiss
authors.forename: Eric P
authors.initials: EP
authors.lastname: Prinssen
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wichmann
authors.forename: Brigitte L
authors.initials: BL
authors.lastname: Kieffer
authors.forename: Abdel-Mouttalib
authors.initials: AM
authors.lastname: Ouagazzal
mesh_terms: D000818:Animals; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D011957:Receptors, Opioid / Q000819:agonists*; D021641:Recognition, Psychology / Q000187:drug effects*; D012601:Scopolamine / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology*; D000094942:Nociceptin Receptor
chemical_list: D018680:Cholinergic Antagonists; D018691:Excitatory Amino Acid Antagonists; D007093:Imidazoles; D016194:Receptors, N-Methyl-D-Aspartate; D011957:Receptors, Opioid; C408068:Ro 64-6198; D013141:Spiro Compounds; D008464:Mecamylamine; D016291:Dizocilpine Maleate; D012601:Scopolamine; D000094942:Nociceptin Receptor; C000722287:Oprl1 protein, mouse