Antidepressant-like effects of the subtype-selective nicotinic acetylcholine receptor agonist, SIB-1508Y, in the learned helplessness rat model of depression.
Psychopharmacology (Berl)
; 152(3): 295-303, 2000 Oct.
Article
en En
| MEDLINE
| ID: mdl-11105940
ABSTRACT
RATIONALE Epidemiological studies of smokers suggest that there is a link between nicotine and depression. Nonetheless, few studies have examined the potential use of nicotinic ligands in the treatment of depression. OBJECTIVES:
The goal of this study was to evaluate the effects of SIB-1508Y, a novel subtype-selective ligand for high affinity nicotinic acetylcholine receptors (nAChRs), in the learned helplessness model of depression in rats.METHODS:
In this model, exposure to inescapable foot-shock produces a lasting deficit in escape responses emitted in a subsequent conditioned avoidance procedure (learned helplessness). The effect of SIB-1508Y on learned helplessness was compared to the clinically used antidepressants, imipramine and fluoxetine, and the non-selective nAChR ligand, nicotine.RESULTS:
Similarly to imipramine and fluoxetine, subchronic treatment (5 days) with SIB-1508Y reversed the escape deficit in the learned helplessness model in a dose dependent manner. The effect of SIB-1508Y on learned helplessness was still apparent 1 week following drug administration and was also maintained after 4 weeks of daily administration. In contrast, while nicotine was able to attenuate the learned helplessness deficit, this trend only reached statistical significance after chronic administration. The non-competitive ion channel blocker mecamylamine increased escape failures when administered alone and blocked the effects of SIB-1508Y but not imipramine. SIB- 1508Y also produced an increase in avoidance responding, which suggests an enhancement of learning.CONCLUSION:
These results not only suggest a role for nAChRs in the development of a depressive-like syndrome, but also that subtype-selective nAChR agonists, such as SIB-1508Y, may offer a novel therapeutic approach to the treatment of depression.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Piridinas
/
Pirrolidinas
/
Agonistas Nicotínicos
/
Depresión
/
Antidepresivos
Límite:
Animals
Idioma:
En
Revista:
Psychopharmacology (Berl)
Año:
2000
Tipo del documento:
Article
País de afiliación:
Estados Unidos