Medicine Poster Session

Paul F. Aravich
aravich@evms

>First, I'd like to congratulate this Discussion Board for lively debate; you have done a terrific job! Second, i'd like to throw in my two cents re OCD and serotonin that may be of interest here. namely, we have made the suggestion for a role of DA in some forms of OCD, and that may relate more closely to Dr Aravich's findings [Szechtman, Sulis and Eilam (1998) Quinpirole induces compulsive checking behavior in rats: a potential animal model of Obsessive-Compulsive Disorder (OCD). Behavioral Neurosciences, December 1998.]
>Cheers, >


Dr. Szechtman:

Thank you so very much for sharing your new publication with us and your data implicating dopamine in a possible animal model of OCD.  I do not yet have access to the current Behavioral Neuroscience (nor is the abstract on PubMed yet), so I cannot comment further about your data with the D2/D3 agonist.  I am aware, however, of other data you published with, e.g., Coscina indicating that chronic treatment with this drug promotes an augmented spontaneous locomotor response (i.e., behavioral sensitization) and potential changes in body lipid utilization.  That your data with Sullivan argues that behavioral sensitization has certain parallels with OCD, which I think is a very intriguing argument. That your data with, e.g., Szumlinski, stresses the environmental modulation of locomotor sensitization.  That your data with Sullivan indicates that mesocortical dopamine depletion worsens restraint-stress ulcers but that this effect is greatest with right frontal depletion.  The interaction between stress and anorexia nervosa is a particularly interesting area and Pare showed many years ago that the model we use for anorexia nervosa and that others use for OCD also is a good model for gastric-stress ulcers.  Now, back to your comment.

Dopamine dysfunction been linked to OCD by others (e.g., McDougle J Clin Psychiatry 1997 58:11-17).  In fact, SRIs in combination with dopamine blockers show some efficacy in OCD patients who are otherwise resistant to SRIs alone (ibid).  Finally, the predominant morphological view of OCD emphasizes an orbital-striatal system that importantly involves an area richly innervated by dopamine, viz., the nucleus accumbens (a topic of discussion in other sessions at this meeting).  Let me review that circuitry and indicate that a dopaminergic view of OCD is not mutually exclusive with a serotonergic view.

The ventral striatum, which is essentially the nucleus accumbens, is the primary striatal target of the orbital cortex.  The ventromedial head of the caudate nucleus (which is effectively the accumbens) is the striatal area that most imaging studies focus on in OCD.  The accumbens also receives important input from the ventral tegmental area (VTA) dopamine system.  The dopamine-accumbens system plays a well-established role in the central substrate of reward, the promotion of repetitive motor behavior (by, e.g., output that ultimately modulates the mesencephalic motor area), and addictive behavior. Koob and others emphasize that chemical dependency is itself a compulsive behavior.  Rapoport's group proposed several years ago that the orbital-striatal system is a filter that releases species-typical behaviors.  One species-typical behavior for rodents and primates is hyperactivity following negative energy balance.  This filter function fits well with the current sensory-gating view of the ventral striatum.  Rapoport and associates also argued that the orbital-striatal system plays an important role in maintaining behavioral escape from threatening stimuli.  The negative energy balance of anorexia nervosa and the anxiety of OCD may be two such stimuli.  We now know that serotonin from the dorsal raphe nucleus promotes dopamine function in the accumbens (Deurwaerdere et al. J Neurosci 1998 18:6528-6538).  Thus, it is possible that resistance to SRIs treatment in some OCD patients and in many patients with anorexic nervosa may be reflective of a serotonin receptor dysfunction that is focused on the accumbens.

Thanks again for your interest in our work.

Paul Aravich