Clenbuterol activates the central IL-1 system via the ß2-adrenoceptor without provoking inflammatory response related behaviours in rats.
Brain Behav Immun
; 56: 114-29, 2016 Aug.
Article
em En
| MEDLINE
| ID: mdl-26928198
ABSTRACT
The long-acting, highly lipophilic, ß2-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-1ß 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, 250µg/kg), clenbuterol (0.5mg/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 ß2-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-1ß. Moreover, despite increasing central IL-1ß expression, chronic administration of clenbuterol (0.03mg/kg; twice daily for 21days) 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 ß2-adrenoceptor agonists could have the potential to combat neuroinflammatory or neurodegenerative disorders without inducing unwanted symptoms of depression and anxiety.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ansiedade
/
Comportamento Animal
/
Clembuterol
/
Depressão
/
Interleucina-1beta
/
Comportamento de Doença
/
Agonistas de Receptores Adrenérgicos beta 2
Limite:
Animals
Idioma:
En
Revista:
Brain Behav Immun
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
CEREBRO
/
PSICOFISIOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Irlanda