Sibutramine antinociceptive effect in female rodents is not dependent on catecholaminergic signaling
- Published
- Accepted
- Subject Areas
- Neuroscience, Pharmacology
- Keywords
- sibutramine, analgesia, thermal hyperalgesia, catecholamines, chronic pain
- Copyright
- © 2015 Sales et al.
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ PrePrints) and either DOI or URL of the article must be cited.
- Cite this article
- 2015. Sibutramine antinociceptive effect in female rodents is not dependent on catecholaminergic signaling. PeerJ PrePrints 3:e1544v2 https://doi.org/10.7287/peerj.preprints.1544v2
Abstract
Sibutramine has a mechanism of action similar to that of antidepressants used as analgesics (like duloxetine). Limited data exists regarding the analgesic action of sibutramine. We tested increasing doses of p.o. sibutramine (0.1, 0.5, 1.5, 5.0 mg/kg) in the writhing test in female mice and in the plantar thermal hyperalgesia induced by carrageenan in female rats. The results showed a statistically significant (p<0.001) dose-response antinociceptive effect of sibutramine in these models, with a maximum effect comparable to the effect of a high dose of ASA (200 mg/kg) in mice and amitriptyline (10mg/kg) or indomethacin (10mg/kg) in rats. Rotarod test with sibutramine-treated rats ruled out motor impairment. Sibutramine-induced antinociception was not reverted by reserpine or yohimbine pre-treatment, suggesting that catecholamines and alpha-2-adrenoceptors are not involved in this effect.
Author Comment
Format-only revision. No content changed from version 1.
Supplemental Information
Microsoft Word - Sales_2011_rev.doc Figure 1: Sibutramine inhibition of acetic acid-induced abdominal writhes in mice
Microsoft Word - Sales_2011_rev.doc Separate groups of 6 mice were administered vehicle or a dose of drug p.o. followed 55 min later by an i.p. injection of 0.55% acetic acid. The total number of writhes made by each mouse was counted between 5 and 20 min after acetic acid administration. Data are expressed as the mean number of writhes during the 15-min observation period. A group was treated with aspirin (ASA) 200 mg/kg and 4 other groups were treated with increasing doses of sibutramine hydrochloride monohydrate (0.1, 0.5, 1.5, and 5.0 mg/kg). Statistical significant difference from control is depicted when present (One-way ANOVA with Tukey as post-hoc test). *** p < 0.001
Microsoft Word - Sales_2011_rev.doc Figure 2: Sibutramine reversal of carrageenan-induced acute thermal hyperalgesia
Microsoft Word - Sales_2011_rev.doc Plantar test was performed as described in methods. SHAM group (SHAM) had no pharmacological treatment. Control group had a 1.0 mg carrageenan plantar injection in right hindpaw 2 h before the test. Treatment groups (SIB 0.1, SIB 0.5, SIB 1.5, SIB 5.0, AMI 10, and INDO 10) were treated with sibutramine 0.1 to 5.0 mg/kg (B), amitriptyline 10 mg/kg or indomethacin 10 mg/kg (A) at the same time of carrageenan injection. A group had sibutramine 1.5 mg/kg treatment but no inflammatory stimulus (SHAM SIB). Reaction time to thermal stimulus (mean ± SD) was plotted. Statistical significant difference from control is depicted when present (One-way ANOVA with Tukey as post- hoc test). * p < 0.05; ** p < 0.01; *** p < 0.001
Microsoft Word - Sales_2011_rev.doc Figure 3: Neither reserpine nor yohimbine did inhibit sibutramine effect
Microsoft Word - Sales_2011_rev.doc Plantar test was performed as described in methods. Animals were pre-treated with reserpine (Sigma), 5.0 mg/kg, administered i.p. (0.2 ml/animal), 6 h before plantar test (B), or with yohimbine 2.0 mg/kg at the same time of p.o. drug treatment (A). Treatment groups (SIB 1.5) were treated with sibutramine 1.5 mg/kg at the same time of carrageenan injection. Reaction time to thermal stimulus (mean ± SD) was plotted. Statistical significant difference from control is depicted when present (One-way ANOVA with Tukey as post- hoc test). * p < 0.05; ** p < 0.01; *** p < 0.001
Microsoft Word - Sales_2011_rev.doc Yohimbine did not inhibit sibutramine effect (raw dataset)
Microsoft Word - Sales_2011_rev.doc Plantar test was performed as described in methods. Animals were pre-treated with yohimbine 2.0 mg/kg at the same time of p.o. drug treatment (io). Treatment groups (sib) were treated with sibutramine 1.5 mg/kg at the same time of carrageenan injection. Reaction time to thermal stimulus in seconds.
Reserpine did not inhibit sibutramine effect (raw dataset)
Microsoft Word - Sales_2011_rev.doc Microsoft Word - Sales_2011_rev.doc Plantar test was performed as described in methods. Animals were pre-treated with reserpine (Sigma), 5.0 mg/kg, administered i.p. (0.2 ml/animal), 6 h before plantar test (RES). Treatment groups (SIB) were treated with sibutramine 1.5 mg/kg at the same time of carrageenan injection. Reaction time to thermal stimulus in seconds.
Microsoft Word - Sales_2011_rev.doc Sibutramine inhibition of acetic acid-induced abdominal writhes in mice (raw dataset)
Microsoft Word - Sales_2011_rev.doc Separate groups of 6 mice were administered vehicle or a dose of drug p.o. followed 55 min later by an i.p. injection of 0.55% acetic acid. The total number of writhes made by each mouse was counted between 5 and 20 min after acetic acid administration. Data are expressed as the number of writhes during the 15-min observation period. A group was treated with aspirin (ASA) 200 mg/kg and 4 other groups were treated with increasing doses of sibutramine hydrochloride monohydrate (0.1, 0.5, 1.5, and 5.0 mg/kg).
Microsoft Word - Sales_2011_rev.doc Sibutramine reversal of carrageenan-induced acute thermal hyperalgesia (raw dataset)
Microsoft Word - Sales_2011_rev.doc Plantar test was performed as described in methods. SHAM group (SHAM) had no pharmacological treatment. Control group had a 1.0 mg carrageenan plantar injection in right hindpaw 2 h before the test. Treatment groups (SIB 0.1, SIB 0.5, SIB 1.5, SIB 5.0, AMI 10, and INDO 10) were treated with sibutramine 0.1 to 5.0 mg/kg, amitriptyline 10 mg/kg or indomethacin 10 mg/kg at the same time of carrageenan injection. A group had sibutramine 1.5 mg/kg treatment but no inflammatory stimulus (SHAM SIB). Reaction time to thermal stimulus in seconds.