Age differences in the sensitivity to clomipramine in an animal model of obsessive-compulsive disorder

Abstract

The present data shows important age differences in the effect of clomipramine in a model of OCD. Such differences could be relevant for the age variations in the response to treatment in clinical practice.

Rodent models of obsessive compulsive disorder: Evaluating validity to interpret emerging neurobiology

“…Instead of spontaneously switching the arm that is entered, rats who receive the drug tend to return repeatedly to the same arm, which may parallel the perseverative behavior often observed in OCD but could also indicate defects in working memory (Dek et al, 2015). Chronic fluoxetine prevents this drug-induced behavior, potentially providing predictive validity; whereas desipramine does not, providing evidence of specificity (Fernandez-Guasti et al, 2003). Importantly, however, diminution of serotonin receptor-mediated behavior with chronic administration of a serotonin reuptake inhibitor is expected due to receptor down-regulation in the context of tonic increases in extracellular serotonin levels.…”

Effects of Thalamic Reticular Nucleus Electrical Stimulation in Rats in a T-maze Perseverative Behavior Model Induced by 8-OH-DPAT

“…Stimulation of TRN at low frequency was highly effective in preventing perseverative behavior induced by 8‐OH‐DPAT, and according to other studies with better results than medical treatment (19,30). The OFF stimulation group did not display any improvement in the behavior and could not prevent the high perseverative effect of the serotonine agonist.…”

“…Apparently, low‐frequency stimulation of the TRN mimics the clinical response of the medical treatment with CMI (19) and surgical lesion; reproducing the functional inhibition that high‐frequency stimulation produces in other nuclei for different diseases (20,21). These results also suggest different findings about the efficacy of high‐frequency stimulation of the mediodorsal thalamic nucleus, the bed nucleus of the stria terminalis, subthalamic nucleus, and the nucleus accumbens described in previous reports that used rats and monkeys; where it proved to decrease the number of perseverations and stereotyped behavior in the animals (14,22–25); in both acute and chronic models.…”

Clomipramine, but not haloperidol or aripiprazole, inhibits quinpirole-induced water contrafreeloading, a putative animal model of compulsive behavior

“…Consistently with the notion that inhibition of serotonin, but not of the noradrenaline transporter, is responsible for the efficacy of CIM in contrasting OCD symptoms, the drug has been also found to prevent perseverative behavior induced by serotonin depletion (Fernandez-Guasti et al 2003). Sensitivity to serotoninergic antidepressants is in fact considered a validation criterion for experimental models of compulsive behavior (Joel 2006;Boulougouris et al 2009).…”