Behavioral indices of beta receptor subsensitivity after chronic treatment with viloxazine in the mouse
R D Porsolt1, A Lenègre, S Miguel
1I.T.E.M.-Labo, Kremlin-Bicêtre, France.
Abstract:
The aim of the experiments was to determine whether chronic pretreatment with viloxazine decreased the sensitivity of mice to the sedative effects of a beta agonist clenbuterol. Mice were subjected to chronic oral treatment with viloxazine (128 mg/kg twice daily) and then given a single administration of 32 mg/kg PO followed by clenbuterol (0.125 mg/kg IP) before being tested in a standard photocell activity meter. Imipramine, administered at the same doses in the same experimental conditions, was used as a comparison compound. The results showed that chronic but not acute viloxazine decreased the hypoactivity induced by clenbuterol, suggesting the induction of beta receptor subsensitivity. With imipramine the results were in the same direction but less clear. The findings are discussed in terms of the eventual specificity of the viloxazine effect to subsensitivity in beta-2 receptors.
Insights
Chronic viloxazine pretreatment reduced mouse sensitivity to the sedative effects of clenbuterol, indicating beta receptor subsensitivity. This suggests viloxazine may specifically impact beta-2 receptors.
Area of Science:
- Pharmacology
- Neuroscience
Background:
- Clenbuterol, a beta-agonist, can induce sedative effects.
- Viloxazine is an antidepressant with potential effects on neurotransmitter systems.
Purpose of the Study:
- To investigate if chronic viloxazine pretreatment alters mouse sensitivity to clenbuterol's sedative effects.
- To explore the potential for viloxazine to induce beta-adrenergic receptor subsensitivity.
Main Methods:
- Mice received chronic oral viloxazine (128 mg/kg twice daily).
- Following pretreatment, mice were administered clenbuterol (0.125 mg/kg IP) and tested for activity.
- Imipramine served as a comparative compound under identical conditions.
Main Results:
- Chronic viloxazine, but not acute, significantly decreased clenbuterol-induced hypoactivity.
- This suggests the development of beta-receptor subsensitivity following chronic viloxazine exposure.
- Imipramine showed similar but less pronounced effects.
Conclusions:
- Chronic viloxazine administration induces subsensitivity to the sedative effects of clenbuterol in mice.
- The findings suggest a potential specific effect of viloxazine on beta-2 adrenergic receptors.
- Further research is warranted to confirm the specificity of viloxazine's action on beta-2 receptors.
