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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kuzmin, Alexander Ogren, Sven Ove Sandin, Johan Terenius, Lars |
| Description | Author Affiliation: Kuzmin A ( Department of Neuroscience, Karolinska Institutet, Stockholm S-171 77, Sweden. alexander.kuzmin@neuro.ki.se) |
| Abstract | 1. The ORL1 agonists nociceptin and Ro 64-6198 were compared in their ability to modify spontaneous locomotor activity in male NMRI mice not habituated to the test environment. 2. Higher doses of nociceptin (>5 nmol i.c.v.) reduced whereas lower doses (<1 nmol i.c.v.) stimulated locomotor activity. Both effects were blocked by the putative ORL1 antagonists [NPhe1]nociceptin(1-13)NH2 (10 nmol i.c.v.) and UFP101 (10 nmol, i.c.v.). The effects were also blocked by naloxone benzoylhydrazone (1 mg x kg(-1) s.c.), but not by the nonselective opioid antagonist naloxone (1 mg x kg(-1) s.c.). 3 In contrast to nociceptin, the synthetic ORL1 agonist Ro 64-6198 (0.01-1.0 mg x kg(-1) i.p.) produced monophasic inhibition of locomotor activity, which was insensitive to the treatment with [NPhe1]nociceptin(1-13)NH2 or naloxone benzoylhydrazone. Treatment with UFP101 abolished the locomotor inhibition induced by Ro 64-6198 (1.0 mg x kg(-1)), whereas naloxone (1.0 mg x kg(-1), s.c.) further increased the locomotor-inhibitory effects. 4. Naloxone benzoylhydrazone (0.3; 1.0 and 3.0 mg x kg(-1) s.c.) increased locomotor activity, although the effect was statistically significant only with the highest dose used. 5. Pretreatment with the tyrosine hydroxylase inhibitor H44-68 totally eliminated the motor-stimulatory effects of low doses of nociceptin, probably via dopamine depletion. 6. The results suggest that nociceptin stimulates locomotor activity at low doses if dopamine activity is intact. High doses of nociceptin and all the tested doses of Ro 64-6198 seem to interact with a functionally different subset of ORL1 receptors. In addition, the effects of Ro 64-6198 are modulated by tonic opioid receptor activity. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 1 |
| Volume Number | 141 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2004-01-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Motor Activity Physiology Naloxone Analogs & Derivatives Receptors, Opioid Animals Cerebrospinal Fluid Chemistry Dose-Response Relationship, Drug Drug Combinations Drug Synergism Imidazoles Administration & Dosage Antagonists & Inhibitors Pharmacokinetics Injections, Intraperitoneal Injections, Intraventricular Injections, Subcutaneous Methyltyrosines Mice Mice, Inbred Strains Drug Effects Narcotic Antagonists Opioid Peptides Spiro Compounds Tyrosine 3-Monooxygenase Comparative Study Research Support, Non-U.S. Gov't Pharmacology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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