Abstract
Rationale
The distribution of oxytocin receptors in limbic regions, as well as evidence that exogenous oxytocin modulates affect and fear processing, suggests that this neuropeptide may have a role to play in the treatment of mood disorders.
Objectives
This study compared the effects of acute treatment with the oxytocin receptor agonist, carbetocin with the tricyclic antidepressant, imipramine, using male Sprague–Dawley rats.
Methods
Intracerebroventricular (i.c.v.; 1, 10, 100 μg/rat), intravenous (i.v.; 2.5, 5 mg/kg), and intraperitoneal (i.p.; 2, 6.4, 20 mg/kg) carbetocin and imipramine (1.8, 5.6, 10 mg/kg, i.p.) were examined in the modified forced swim and open field tests. The mechanism of action of carbetocin was investigated by co-administering it with the oxytocin antagonist, atosiban, either centrally (5 μg/rat, i.c.v.) or systemically (1 mg/kg, i.v.).
Results
Imipramine and carbetocin (all three routes of administration) both significantly reduced immobility and increased swimming and/or climbing behavior in the forced swim test. The systemic effects of carbetocin were blocked by central and systemic atosiban co-administration. Only amphetamine (2 mg/kg, i.p.), included as a false positive in order to distinguish whether antidepressant-like effects were due to psychomotor stimulation, increased locomotor activity in the open field test.
Conclusions
Carbetocin produced antidepressant-like changes in behavior via activation of oxytocin receptors in the CNS. The similarities between imipramine and carbetocin in the forced swim test suggest that drugs which target the oxytocinergic system may aid both the understanding and pharmacological treatment of depressive illness.
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Abbreviations
- i.p.:
-
intraperitoneal
- i.c.v.:
-
intracerebroventricular
- i.v.:
-
intravenous
- f.s.t.:
-
forced swimming test
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Acknowledgements
The authors wish to thank Julia Ross and Terry Lane for their willing and capable technical assistance, Qiong Yue Teo for her enthusiasm with setting up the behavioral software, and Associate Professor Jenny Redman for her insights during the planning stages of this project. A preliminary report of this paper was presented at the International Brain Research Organization Meeting in July 2007. This work was funded in part by a Monash University Early Career Researcher Grant (awarded to JB).
The animal experiments reported in this manuscript comply with the regulations of the Bureau of Animal Welfare, Department of Primary Industries, Australia.
Disclosure/Conflict of Interest
None of the authors have any potential or actual conflict of interest to declare; none of the authors have received or anticipated receiving compensation of any kind for professional services from external organizations.
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Chaviaras, S., Mak, P., Ralph, D. et al. Assessing the antidepressant-like effects of carbetocin, an oxytocin agonist, using a modification of the forced swimming test. Psychopharmacology 210, 35–43 (2010). https://doi.org/10.1007/s00213-010-1815-x
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DOI: https://doi.org/10.1007/s00213-010-1815-x