The aim of the present paper is to report on the adrenergic and serotonergic effects of besipirdine (HP 749) in vivo and to discuss its potential use in the treatment of obsessive compulsive disorder. Besipirdine inhibited biogenic amine uptake in vitro. It prevented tetrabenazine-induced ptosis in mice and potentiated the 5-hydroxytryptophan-induced serotonin syndrome in rats. Furthermore, it decreased schedule-induced polydipsic behavior in rats. Schedule-induced polydipsia may be a model for obsessive compulsive disorder. Previous results from our group have shown that certain selective serotonin reuptake inhibitors decrease schedule-induced polydipsia after 14-21 days of treatment. Besipirdine reduced schedule-induced polydipsic behavior immediately and this reduction lasted throughout the duration of the experiment (29 days).
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Brain Commun
May 2024
Department of Psychology, CLIC (Cambridge Laboratory for Research on Impulsive/Compulsive Disorders), University of Cambridge, Cambridge CB2 3EB, UK.
Only some vulnerable individuals who recreationally drink alcohol eventually develop the compulsive drinking pattern that characterizes alcohol use disorder. A new frontier in biomedical research lies in understanding the neurobehavioural mechanisms of this individual vulnerability, a necessary step towards developing novel effective therapeutic strategies. Translational research has been hindered by the lack of valid, reliable and robust approaches that enable the study of the influence of the reliance on alcohol to cope with stress or self-medicate negative emotional states on the subsequent transition to alcohol use disorder.
View Article and Find Full Text PDFJ Med Chem
February 2024
Drug Discovery, Idorsia Pharmaceuticals Ltd., Hegenheimermattweg 91, 4123 Allschwil, Switzerland.
The orexin system consists of two neuropeptides (orexins A and B) and two receptors (OX1 and OX2). Selective OX1 receptor antagonists (SO1RA) are gaining interest for their potential use in the treatment of CNS disorders, including substance abuse, eating, obsessive compulsive, or anxiety disorders. While blocking OX2 reduces wakefulness, the expected advantage of selectively antagonizing OX1 is the ability to achieve clinical efficacy without the promotion of sleep.
View Article and Find Full Text PDFBehav Brain Funct
November 2023
Department of Psychology and Health Research Centre (CEINSA), University of Almería, Carretera de Sacramento s/n, 04120, Almería, Spain.
Compulsivity is considered a transdiagnostic dimension in obsessive-compulsive and related disorders, characterized by heterogeneous cognitive and behavioral phenotypes associated with abnormalities in cortico-striatal-thalamic-cortical circuitry. The present study investigated the structural morphology of white and gray matter in rats selected for low- (LD) and high- (HD) compulsive drinking behavior on a schedule-induced polydipsia (SIP) task. Regional brain morphology was assessed using ex-vivo high-resolution magnetic resonance imaging (MRI).
View Article and Find Full Text PDFLearn Behav
December 2023
Laboratorio de Aprendizaje y Conducta Animal, Facultad de Psicología, Universidad Nacional de Educación a Distancia, C/ Juan del Rosal 10, Ciudad Universitaria, 28040, Madrid, Spain.
Mol Neurobiol
December 2023
Department of Psychology and Health Research Center CEINSA, University of Almería, Ctra. Sacramento, s/n, 04120, Almería, Spain.
Compulsivity is a core symptom in different psychopathological disorders, characterized by excessive behaviors and behavioral inflexibility. The selection of high drinker (HD) versus low drinker (LD) rats by schedule-induced polydipsia (SIP) is a valid model for studying the compulsive phenotype. The compulsive HD rats showed cognitive inflexibility and reduced serotonin 2A (5-HT2A) receptor binding levels in the frontal cortex (FC).
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