Antidepressant-like effects of the subtype-selective nicotinic acetylcholine receptor agonist, SIB-1508Y, in the learned helplessness rat model of depression
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.
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Several classes of nicotinic agonists have antidepressant actions in human studies and animal models, but several nicotinic antagonists have potent antidepressant effects.
“several classes of nicotinic agonists have antidepressant actions in both human studies and animal models (Ferguson et al., 2000; Gatto et al., 2004) but several nicotinic antagonists have shown to have potent antidepressant effects (Ferguson et al., 2000; Shytle et al., 2002).”
From It is not “either/or”: Activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood (2008) · cites this paper as Ferguson et al., 2000
In the learned helplessness model, nicotine gives antidepressant-like effects only after chronic, not acute, administration.
“Furthermore, chronic, but not acute, administration of nicotine elicits antidepressant-like effects in the learned helplessness model of depression (Ferguson et al., 2000).”
From Nicotinic Partial Agonists Varenicline and Sazetidine-A Have Differential Effects on Affective Behavior (2010) · cites this paper as Ferguson et al., 2000
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- Authors
- Ferguson, S. M., Brodkin, J. D., Kenneth Lloyd, G., & Menzaghi, F.
- Venue
- Psychopharmacology
- Published
- 2000-08-29
- Volume
- 152
- Issue
- 3
- Pages
- 295-303
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2071894558
- Cited by
- 85
- References
- 31
- Citations by year
- 2025: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 7 · 2015: 4 · 2014: 4 · 2013: 5 · 2012: 2
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- nicotinic acetylcholine receptors, subtype-selective agonists, depression, learned helplessness, nicotine, mecamylamine, imipramine, fluoxetine, antidepressant effects, escape behavior, avoidance learning
- MeSH terms
- Animals, Antidepressive Agents, Avoidance Learning, Depression, Dose-Response Relationship, Drug, Imipramine, Male, Mecamylamine, Nicotine, Pyridines, Pyrrolidines, Rats, Sprague-Dawley, Nicotinic Agonists, Rats
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