Effect of multiple injections of U-50, 488H, a kappa-opioid receptor agonist, on the activity of nitric oxide synthase in brain regions and spinal cord of mice.
1. The time course of the effects of multiple injections of U-50,488H, a kappa-opioid receptor agonist, and its subsequent termination on its analgesic action and nitric oxide synthase (NOS) activity was determined in the brain regions and spinal cord of the mouse. 2. Male Swiss-Webster mice were rendered tolerant to U-50,488H by twice-daily injections of the drug (25 mg/kg, IP) for 4 days. Vehicle-injected mice served as controls. 3. In tolerant mice, NOS activity was unchanged in brain regions and the spinal cord after treatment with U-50,488H. During abstinence from U-50,488H, NOS activity was found to be increased in the cortex and remainder of the brain, but no change was noted in the cerebellum, midbrain and spinal cord. 4. These studies demonstrate that withdrawal from the short-term treatment with U-50,488H in mice causes induction of NOS in certain brain regions. However, long-term treatment and withdrawal from U-50,488H are not associated with changes in the central NOS activity and indicate a possible adaptation in the NOS activity.
Bhargava
H N
HN
Department of Pharmaceutics and Pharmacodynamics, University of Illinois at Chicago, Health Sciences Center, Illinois 60612, USA. DRHNB@UIC.EDU
Kumar
S
S
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010147:Pain Measurement / Q000187:drug effects; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology*; D013375:Substance Withdrawal Syndrome / Q000201:enzymology
D000700:Analgesics; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D019001:Nitric Oxide Synthase