Event Information:

• Wed

  20

  Nov

  2019

  Seminar: Exploring the therapeutic potential of the endocannabinoid system in psychiatric symptoms of Huntington’s disease

  13hAula 16, Faculty of Medicine, Campus Clínic

  Josep F. Cheer, Ph.D - University of Maryland School of Medicine

  Abstract

  It has been posited that compromised motivation in HD or “apathy” arises from a deficit in preparing for and initiating goal-directed behavior. Apathy is always the primary deficit in motivation associated with frontal-subcortical diseases such as HD. Indeed, apathy may be a core feature of HD pathology itself. In many cases apathy follows a similar trajectory as motor symptom progression in HD, although it can become prevalent before phenoconversion. It can be the result of several neurobiologically maladaptive systems, including affective (flattening of emotional responsiveness), behavioral (reduced initiation of spontaneous behavior), and executive dysfunction (difficulty planning/executing). Thus, motivational dysfunction in HD is a deficit primarily in preparation for motivated behavior that can have debilitating co-morbid consequences.

  Gaps in knowledge

  ·      Loss of striatal cannabinoid type 1 (CB1) receptors is a key pathogenic of several neurodegenerative diseases, including HD.

  ·      Treatment for metabolic syndrome with the CB1 receptor antagonist Rimonabant was halted by the FDA because of loss of motivation and depressive ideation.

  ·      HD patients tend to smoke marijuana as a way to self-medicate and to prevent feelings of loneliness and helplessness.

  ·      Loss of goal-directed behavior in HD is specific to the incentive value of the reinforcer.

  Treatment with indirect cannabinoid agonists profoundly increases operationally defined indices of motivation in normal animals and reverses apathy via dopaminergic mechanisms in mouse models of HD.