Assessing the antidepressant-like effects of carbetocin, an oxytocin agonist, using a modification of the forced swimming test

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 microg/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 microg/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.