Tryptophan depletion affects compulsive behaviour in rats: strain dependent effects and associated neuromechanisms

A Merchán,P Flores,S V Navarro,M Moreno,S Aznar,C Suñol,L Campa,A B Klein

doi:10.1007/s00213-017-4561-5

Abstract

RationaleCompulsive behaviour, present in different psychiatric disorders, such as obsessive-compulsive disorder, schizophrenia and drug abuse, is associated with altered levels of monoamines, particularly serotonin (5-hydroxytryptamine) and its receptor system.ObjectivesThe present study investigated whether 5-HT manipulation, through a tryptophan (TRP) depletion by diet in Wistar and Lister Hooded rats, modulates compulsive drinking in schedule-induced polydipsia (SIP) and locomotor activity in the open-field test. The levels of dopamine, noradrenaline, serotonin and its metabolite were evaluated, as well as the 5-HT2A and 5-HT1A receptor binding, in different brain regions.MethodsWistar rats were selected as high (HD) or low (LD) drinkers according to their SIP behaviour, while Lister hooded rats did not show SIP acquisition. Both strains were fed for 14 days with either a TRP-free diet (T−) or a TRP-supplemented diet (T+)ResultsThe TRP depletion diet effectively reduced 5-HT levels in the frontal cortex, amygdala and hippocampus in both strains of rats. The TRP-depleted HD Wistar rats were more sensitive to 5-HT manipulation, exhibiting more licks on SIP than did the non-depleted HD Wistar rats, while the LD Wistar and the Lister Hooded rats did not exhibit differences in SIP. In contrast, the TRP-depleted Lister Hooded rats increased locomotor activity compared to the non-depleted rats, while no differences were found in the Wistar rats. Serotonin 2A receptor binding in the striatum was significantly reduced in the TRP-depleted HD Wistar rats.ConclusionsThese results suggest that alterations of the serotonergic system could be involved in compulsive behaviour in vulnerable populations.

Highlights

Compulsivity represents the performance of repetitive and functionally impairing overt or covert behaviours without adaptive function, performed in a habitual or stereotyped fashion, either according to rigid rules or as a means of avoiding perceived negative consequences (Fineberg et al 2014)
Before TRP depletion by diet, we examined between-strain differences in the model of compulsive behaviour, schedule-induced polydipsia (SIP), and we found in the Wistar strain two groups of rats based on their drinking behaviour, high or excessive drinking (HD) and low drinkers (LD), while the LH strain did not show acquisition of compulsive drinking
After the chronic TRP depletion by diet, the TRP-depleted HD group of Wistar rats increased their compulsive drinking based on the total number of licks, but no changes in drinking behaviour were observed in either the LD Wistar or LH rats

Summary

Introduction

Compulsivity represents the performance of repetitive and functionally impairing overt or covert behaviours without adaptive function, performed in a habitual or stereotyped fashion, either according to rigid rules or as a means of avoiding perceived negative consequences (Fineberg et al 2014). Neuropsychiatric disorders characterized by compulsivity are included in the newly created Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) Bobsessive-compulsive and related disorders^ (OCRDs) cluster, such as obsessivecompulsive disorder (OCD), body dysmorphic disorder, trichotillomania (repetitive hair pulling), hoarding disorder and excoriation (skin-picking) (American Psychiatric Association 2013). This behaviour is present across different disorders, such as schizophrenia, attention-deficit hyperactivity disorder (ADHD), pathological gambling, eating disorders, depression or substance addiction (Skodol and Oldham 1996). Studies on 5-HT depletion by excitotoxic lesions in rats have revealed an increase of perseverative responding in the five-choice serial reaction time task (Winstanley et al 2004), impairment of behavioural flexibility measured through the reversal learning task (Bari et al 2010; Lapiz-Bluhm et al 2009; Wallace et al 2014) and an increment of compulsive cocaine seeking under punishment (Pelloux et al 2012)

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