PS144. Dopamine D1 receptor in the medial prefrontal cortex mediates behavioral resilience under stress in mice

s | 49 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 openfield 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.