In this thesis, we have studied the potential of the zebrafish larval model in studying the ECS, as a complementary model to the existing rodent models. More specifically, we have looked at the... Show moreIn this thesis, we have studied the potential of the zebrafish larval model in studying the ECS, as a complementary model to the existing rodent models. More specifically, we have looked at the role of the ECS in regulating locomotion and anxiety, and its interaction with the hypothalamic-pituitary-interrenal (HPI) axis, or stress axis. This study has provided us with an interesting animal model which allows for pharmacological screening of Cnr1 agonists, and their involvement in the CNS, as shown by a change in locomotion, anxiety-like behavior and HPI axis activity. The zebrafish larval model can be used as a complementary model to the existing rodent animal models, to study the ECS. The zebrafish larval model brings several interesting features, such as optical transparency and possibilities for high-throughput screening. Furthermore, a complete ECS is present, there is lack of endogenous activity, allowing for exogenous compound screening, and zebrafish data is generally in line with rodent literature. Since the ECS is involved in many diseases, more research of this system may result in the discovery of novel drugs and drug targets. Show less
In a clinical sample of 116 children and adolescents we studied the relation between the course of an anxiety disorder during treatment and the concomitant changes in cortisol levels. Assessments... Show moreIn a clinical sample of 116 children and adolescents we studied the relation between the course of an anxiety disorder during treatment and the concomitant changes in cortisol levels. Assessments at base-line, after three months, and at one-year follow-up were performed with the Anxiety Disorders Interview Schedule. When we compared cortisol levels at baseline and one-year follow-up, persistence of the anxiety disorder was associated with both increased daytime cortisol production (F = 3.2, p = 0.04) and a trend towards a decreased cortisol morning rise (F = 2.4, p = 0.09). At one-year follow-up daytime cor-tisol production was lowest in the early remitters (109.7 ± 29.2 h mmol/l), higher in the late remitters (121.0 ± 40.0 h mmol/l) and highest in the non-remitters (131.1 ± 48.9 h mmol/l). Early remitters had the highest cortisol morning rise (1.1 ± 1.5 h mmol/l), followed by the late remitters (0.8 ± 1.8 h mmol/l), the non-remitters had the lowest cortisol morning rise (0.07 ± 1.7 h mmol/l). Persistence of an anxiety disorder may thus lead to changes in HPA-axis functioning, underscoring the importance adequate treatment of anxiety disorders. Show less