Nicolaj Daugaard
-
![]()
nda@sdu.dk
PhD Student
A translational cross-site study examining the validity of a novel animal model of OCD-like behaviour, and the treatment potential of psilocybin
Obsessive-compulsive disorder (OCD) is a highly heterogeneous and refractory neuropsychiatric disease. The search for novel therapies is hampered by difficulties in translating the disorder to animal models. The anterior cingulate cortex (ACC) has been implicated in the pathology, though its role is still not clearly understood. Selective serotonin reuptake inhibitors (SSRIs) are standard treatment for OCD, and the serotonergic system in general has been widely implicated. Early evidence indicates that the efficacy of the serotonergic agonist psilocybin (PSI) should be investigated further. AIM1: By inducing the expression of designer receptors exclusively activated by designer drugs (DREADDs) I will enable temporary hyperactivation of the ACC-dorsomedial striatal (dMS) pathway in rats by injection of an exogenous agonist of the DREADDs. Through a battery of automated cognitive testing assessing the presence of OCD-like compulsive behaviour and cognitive flexibility, we will get a unique view on the causal role of the ACC-dMS-pathway. AIM2: Using the above mentioned cognitive testing scheme, I will test the effects of PSI in healthy humans and compare the effects of PSI and the SSRI escitalopram in wildtype rats allowing for direct analysis of the translational value of the model and setup. AIM3: Finally, I will compare the efficacy of PSI- and SSRI-treatment in ameliorating the impairments incurred in the DREADD-model. Considering the refractory nature of OCD, elucidating the role of the ACC-dMS-pathway, the neurochemical mechanisms and effect of PSI and the behavioural profile of OCD, is of great importance.
Obsessive-compulsive disorder (OCD) is a highly heterogeneous and refractory neuropsychiatric disease. The search for novel therapies is hampered by difficulties in translating the disorder to animal models. The anterior cingulate cortex (ACC) has been implicated in the pathology, though its role is still not clearly understood. Selective serotonin reuptake inhibitors (SSRIs) are standard treatment for OCD, and the serotonergic system in general has been widely implicated. Early evidence indicates that the efficacy of the serotonergic agonist psilocybin (PSI) should be investigated further. AIM1: By inducing the expression of designer receptors exclusively activated by designer drugs (DREADDs) I will enable temporary hyperactivation of the ACC-dorsomedial striatal (dMS) pathway in rats by injection of an exogenous agonist of the DREADDs. Through a battery of automated cognitive testing assessing the presence of OCD-like compulsive behaviour and cognitive flexibility, we will get a unique view on the causal role of the ACC-dMS-pathway. AIM2: Using the above mentioned cognitive testing scheme, I will test the effects of PSI in healthy humans and compare the effects of PSI and the SSRI escitalopram in wildtype rats allowing for direct analysis of the translational value of the model and setup. AIM3: Finally, I will compare the efficacy of PSI- and SSRI-treatment in ameliorating the impairments incurred in the DREADD-model. Considering the refractory nature of OCD, elucidating the role of the ACC-dMS-pathway, the neurochemical mechanisms and effect of PSI and the behavioural profile of OCD, is of great importance.