Dopamine-ghrelin interactions as novel targets for therapy resistant anxiety disorders

Project Details


Anxiety disorders are the most common cause of psychiatric illness and are characterized by excessive fear. Many patients do not respond sufficiently to available treatments such as exposure therapy. This stresses the need for novel therapeutic approaches including non-classical targets such as neuropeptide systems. In mice, diet-induced obesity induces ghrelin resistance and high anxiety whereas caloric restriction reverses ghrelin resistance and decreases anxiety. This suggests that ghrelin resistance, the inability of ghrelin to activate its receptors in the brain, is a common factor in eating disorders and anxiety disorders. Ghrelin receptors are highly expressed on nerve cells that produce the neurotransmitter dopamine. These dopamine neurons control exposure-induced extinction of fear memory. We will investigate whether treatment resistance in anxiety disorders is related to altered ghrelin action on dopamine neurons. Central to our innovative research proposal is the use of a psychopathological mouse model with high relevance to human anxiety disorders that will allow us to identify maladaptive changes within the fear extinction circuit underlying treatment resistance. We propose that targeting ghrelin actions on neurons, directly using pharmacological tools, or indirectly through dietary restriction, may open new avenues to counter excessive fear by facilitating fear extinction.
Effective start/end date1/01/1631/12/18


  • Anxiety disorder

Flemish discipline codes

  • Pharmacology not elsewhere classified