Effects of nociceptin on the exploratory behavior of mice in the hole-board test.
The effects of nociceptin on the exploratory behavior of mice were examined using an automatic hole-board apparatus. A low dose of nociceptin (0.01 nmol, i.c.v.) had an anxiolytic effect, as reflected by an increase in head-dipping behavior. However, high doses of nociceptin (1-5 nmol, i.c.v.) produced a dose-dependent anxiogenic effect, as reflected by a decrease in head-dipping behavior. Both the anxiolytic and anxiogenic effects of nociceptin were antagonized by nocistatin, an opioid receptor-like 1 (ORL1) receptor antagonist. Although a low dose (0.01 nmol, i.c.v.) of nociceptin significantly increased the rate of serotonin (5-hyroxytryptamine, 5-HT) turnover in the hippocampus, a high dose (5 nmol, i.c.v.) of nociceptin significantly decreased this turnover in the amygdala. Furthermore, the anxiolytic effect of nociceptin at a low dose was antagonized by N-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-N-(2-pyridinyl) cyclo-hexanecarboxamide 3HCl (WAY100635), a 5-HT1A receptor antagonist. On the other hand, the anxiogenic effect of nociceptin at a high dose was antagonized by R(+)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (8-OH-DPAT), a 5-HT1A receptor agonist. In conclusion, the results of this study suggest that nociceptin has dose-related anxiolytic and anxiogenic effects as a result of the activation of ORL1 receptors. The present results also suggest that a low dose of nociceptin has an anxiolytic effect via the activation of 5-HT ergic function in the hippocampus, while a high dose of nociceptin has an anxiogenic effect via the inhibition of 5-HT ergic function in the amygdala.
Kamei
Junzo
J
Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 4-41, Ebra 2-chrome, Shinagawa, Tokyo 142-8501, Japan. kamei@hoshi.ac.jp
Matsunawa
Yasuhiro
Y
Miyata
Shigeo
S
Tanaka
Shun-ichi
S
Saitoh
Akiyoshi
A
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D004644:Emotions / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018847:Opioid Peptides / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012701:Serotonin / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D000097629:Nociceptin
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000701:Analgesics, Opioid; D006897:Hydroxyindoleacetic Acid; D018847:Opioid Peptides; D010879:Piperazines; D011725:Pyridines; D012701:Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D000097629:Nociceptin; C111148:nocistatin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide