title: Morphine-induced Straub tail reaction in mice treated with serotonergic compounds.
abstract: Constitutively active 5-HT2receptors have been suggested to contribute to motoneuronal excitability, muscle spasms and spasticity. Accordingly, 5-HT2Creceptor inverse agonists have been demonstrated in pilot experiments to reduce spasticity in animal model of spasticity and patients with spinal cord injuries. Thus, 5-HT2Creceptor inverse agonists may represent a novel class of anti-spasticity agents justifying a search for compounds with robust 5-HT2Creceptor inverse agonist activity either among the existing medications or via a dedicated drug discovery program. Morphine-induced Straub tail response in mice is regarded as a model of transient spasticity that may be suitable for supporting such drug discovery efforts. Subcutaneous injection of morphine (10-60mg/kg) induced a dose-dependent Straub tail reaction in male Swiss mice with maximum response obtained 15-30min after the morphine administration. When given prior to morphine, 5-HT2B/2Creceptor inverse agonists cyproheptadine (1-10mg/kg, i.p.) and SB206553 (0.3-3mg/kg, i.p.) diminished Straub tail reaction dose-dependently without affecting spontaneous locomotor activity. In contrast, 5-HT2B/2Creceptor antagonist methysergide (1-5.6mg/kg, i.p.) and 5-HT2Creceptor antagonist SB242084 (1-5.6mg/kg, i.p.) as well as 5-HT2Areceptor inverse agonist pimavanserin (1-10mg/kg, i.p.) had no appreciable effects on Straub tail response. Taken together, the findings indicate that constitutive activity of 5-HT2B/2Creceptor may be involved in the mechanisms of morphine-induced spasticity. Thus, morphine-induced Straub tail response may be evaluated further as a candidate higher throughput test to identify 5-HT2Creceptor inverse agonists with anti-spasticity effects in vivo.
authors: Department of Psychopharmacology, Valdman Institute of Pharmacology, First Pavlov State Medical University of St. Petersburg, 6-8 Lev Tolstoy Street, St. Petersburg 197022, Russian Federation.
authors: Irina V
authors: IV
authors: Belozertseva
authors: Department of Psychopharmacology, Valdman Institute of Pharmacology, First Pavlov State Medical University of St. Petersburg, 6-8 Lev Tolstoy Street, St. Petersburg 197022, Russian Federation. Electronic address: olga.dravolina@gmail.com.
authors: Olga A
authors: OA
authors: Dravolina
authors: Department of Psychopharmacology, Valdman Institute of Pharmacology, First Pavlov State Medical University of St. Petersburg, 6-8 Lev Tolstoy Street, St. Petersburg 197022, Russian Federation.
authors: Margarita A
authors: MA
authors: Tur
authors: Department of Psychopharmacology, Valdman Institute of Pharmacology, First Pavlov State Medical University of St. Petersburg, 6-8 Lev Tolstoy Street, St. Petersburg 197022, Russian Federation.
authors: Marina G
authors: MG
authors: Semina
authors: Department of Psychopharmacology, Valdman Institute of Pharmacology, First Pavlov State Medical University of St. Petersburg, 6-8 Lev Tolstoy Street, St. Petersburg 197022, Russian Federation.
authors: Edwin E
authors: EE
authors: Zvartau
authors: Department of Psychopharmacology, Valdman Institute of Pharmacology, First Pavlov State Medical University of St. Petersburg, 6-8 Lev Tolstoy Street, St. Petersburg 197022, Russian Federation.
authors: Anton Yu
authors: AY
authors: Bespalov
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D054314:Drug Inverse Agonism; D007700:Kinetics; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009128:Muscle Spasticity / Q000139:chemically induced* / Q000178:diet therapy* / Q000188:drug therapy / Q000503:physiopathology; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D009020:Morphine
keywords: 5-HT(2) receptor; Cyproheptadine; Mice; SB206553; Straub tail reaction; Transient spasticity