Effect of clomipramine on monoamine metabolites in the cerebrospinal fluidof behaviorally normal dogs

The tricyclic antidepressant, clomipramine, is an effective treatment for c anine compulsive disorder (canine CD). This disorder is a clinical syndrome of abnormal conflict behaviors and its pathophysiology is unknown. However , because clomipramine is an effective treatment, information about the dru g's neurochemical effect could enhance the understanding of canine CD. The following experiment used 6 behaviorally normal dogs to assess the effect o f clomipramine (3 mg/kg, q24h, PO) on the central turnover of 3 monoamines (serotonin, dopamine, and norepinephrine) as measured by the concentrations of their respective metabolites in cerebrospinal fluid (CSF). In a randomi zed, placebo-controlled, AB-BA crossover experiment, cisternal CSF was take n after 1, 2, 4, and 6 wk on each treatment. No effect of clomipramine was detected. This contrasts with human studies that have suggested that clomip ramine affects the concentrations of monoamine metabolites in lumbar CSF. H owever, those papers do not address methodological assumptions, such as (i) metabolites in CSF originate only from the brain, and (ii) concentrations of metabolites in cisternal/lumbar CSF reflect the concentrations in local areas of the brain. Notwithstanding the small sample size, our results sugg est that more localized sampling techniques (e.g. microdialysis) are needed when examining the effect of drugs on central monoamine metabolites. Clomi pramine's efficacy for canine CD indicates the need for neurobiological res earch and, to our knowledge, our study is the first of its kind in dogs. Th e resulting data are preliminary but they can inform optimal neurobiologica l studies of canine CD.