Ryan, Karen M. and Griffin, Éadaoin W. and Ryan, Katie J. and Tanveer, Riffat and Vanattou-Saifoudine, Natacha and McNamee, Eóin N. and Fallon, Emer and Heffernan, Sheena and Harkin, Andrew and Connor, Thomas J.
(2016)
Clenbuterol activates the central IL-1 system via the b2-adrenoceptor
without provoking inflammatory response related behaviours in rats.
Brain, Behavior, and Immunity, 56.
pp. 114-129.
ISSN 0889-1591
Abstract
The long-acting, highly lipophilic, b2-adrenoceptor agonist clenbuterol may represent a suitable therapeutic agent for the treatment of neuroinflammation as it drives an anti-inflammatory response within
the CNS. However, clenbuterol is also known to increase the expression of IL-1b in the brain, a potent
neuromodulator that plays a role in provoking sickness related symptoms including anxiety and
depression-related behaviours. Here we demonstrate that, compared to the immunological stimulus
lipopolysaccharide (LPS, 250 lg/kg), clenbuterol (0.5 mg/kg) selectively up-regulates expression of the
central IL-1 system resulting in a mild stress-like response which is accompanied by a reduction in locomotor activity and food consumption in rats. We provide further evidence that clenbuterol-induced activation of the central IL-1 system occurs in a controlled and selective manner in tandem with its negative
regulators IL-1ra and IL-1RII. Furthermore, we demonstrate that peripheral b2-adrenoceptors mediate the
suppression of locomotor activity and food consumption induced by clenbuterol and that these effects
are not linked to the central induction of IL-1b. Moreover, despite increasing central IL-1b expression,
chronic administration of clenbuterol (0.03 mg/kg; twice daily for 21 days) fails to induce anxiety or
depressive-like behaviour in rats in contrast to reports of the ability of exogenously administered IL-1
to induce these symptoms in rodents. Overall, our findings suggest that clenbuterol or other selective
b2-adrenoceptor agonists could have the potential to combat neuroinflammatory or neurodegenerative
disorders without inducing unwanted symptoms of depression and anxiety.
| Item Type: |
Article
|
| Keywords: |
b2-Adrenoceptor;
Clenbuterol;
Cytokine;
IL-1b;
Locomotor activity;
Food consumption;
Sickness behaviour;
Anhedonia;
Anxiety;
Depression; |
| Academic Unit: |
Faculty of Science and Engineering > Biology |
| Item ID: |
12569 |
| Identification Number: |
https://doi.org/10.1016/j.bbi.2016.02.023 |
| Depositing User: |
Eoin McNamee
|
| Date Deposited: |
19 Mar 2020 17:34 |
| Journal or Publication Title: |
Brain, Behavior, and Immunity |
| Publisher: |
Elsevier |
| Refereed: |
Yes |
| URI: |
|
| Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
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