Abstract
Background: Clinical studies show that ketamine, an NMDA receptor antagonist, produces a rapid and sustained antidepressant response, while classical antidepressants require repeated treatment for up to four weeks to produce similar effects1. Due to the high number of individuals with affective disorders, which are resistant to the established monoaminergic drug therapies, there is a great need to develop novel and more effective antidepressants1. Ketamine has a potential to be applied as an alternative intervention to patients with treatment resistant depression2, but given methodological difficulties there are only few studies evaluating its effects in adequate animal models.
Aims: This project aims to assess whether systemic treatment with ketamine may improve the behavioural response in an animal model of a treatment resistant condition.
Methods: Male Sprague-Dawley rats received subcutaneous injections of ACTH (100ug/rat/day) or vehicle during 14 days. On the 14th day the animals were exposed to the pre-test session of forced swim (FST) and after 24h they were exposed to the open-field test (OFT) followed by the FST test session. The animals received an intraperitoneal injection of ketamine (15 mg/kg) or vehicle or imipramine (3 injections of 15 mg/kg) 1h before the test session.
Results: The immobility time during the pre-test was increased on the group treated with ACTH (F(14,37)=3,484; *p<0,05; Dunnett). Ketamine, but not imipramine, reduced the immobility time when exposed to the test session (F(2,16)=4,002; *p<0,05; Dunnett). The OFT showed that the drugs did not increase the locomotor activity.
Conclusion: The data suggest that ACTH treatment can induce a pro-depressive-like effect, which highlights its role as an inducer of a treatment-resistant condition. The results reinforce the potential antidepressant-like effects of ketamine in a treatment resistant condition, thus corroborating the literature findings. Further studies are necessary to investigate the mechanisms which ketamine induces its effects on treatment resistant rats.
Keywords: depression, antidepressants, ketamine, treatment resistant.
References
1Sanacora, G. et al., 2008. Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nat. Rev. Drug Discov. 7, 426–437.
2Zarate CA, et al., 2006A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 63(8): 856–864.