Altered open-field behavior in experimental chronic hepatic encephalopathyafter single venlafaxine and citalopram challenges

Rationale: Latent or manifest chronic hepatic encephalopathy (HE) symptomat ology often includes affective symptoms. It is therefore warranted to inves tigate the functional outcome of novel antidepressants when chronic HE prev ails. Objective: Portacaval shunt (PCS) in rats is a widely used experiment al model for chronic HE, a neuropsychiatric syndrome accompanying liver dys function. HE is believed to arise from a primary alteration in neurotransmi ssion in the CNS. PCS has been reported to increase the metabolism of serot onin in the brain, and thus the central serotonin nerve of PCS rats may con tain more serotonin than normal. However, the functional relevance of this serotonergic alteration in terms of affecting behavioral performance of PCS rats has been only rarely studied. Methods: Locomotor and rearing activiti es were recorded in PCS and sham-operated control rats. A single subcutaneo us challenge with saline versus either the mixed serotonin/noradrenaline re uptake inhibitor venlafaxine (10 mg x kg(-1)) or the selective serotonin re uptake inhibitor citalopram (5 mg x kg(-1)) were performed. Results: The PC S-saline injected rats showed reduced locomotor and rearing activity compar ed with sham-saline treated rats. While no significant differences could be observed following the venlafaxine challenge to controls, the PCS-venlafax ine challenged rats displayed reduced behavioral activity as compared to PC S-saline treated rats. The PCS-citalopram rats, however, displayed increase d activity compared with the PCS-saline rats while, again,. no effect of th e citalopram challenge to controls was found. Conclusions: The present stud y show altered but opposite:behavior in PCS rats, when challenged with eith er venlafaxine or citalopram, compared to PCS control rats. These findings therefore support the contention that caution should be advocated when CNS monoamine active drugs are used in liver-impaired subjects until better del ineation of the combined pharmacodynamic and pharmacokinetic outcome for ea ch such drug in this condition has been made.