title: Tryptophan depletion affects compulsive behaviour in rats: strain dependent effects and associated neuromechanisms.
abstract: Compulsive 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.
  
  
  
  The 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-HT2Aand 5-HT1Areceptor binding, in different brain regions.
  
  
  
  Wistar 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+) RESULTS: The 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.
  
  
  
  These results suggest that alterations of the serotonergic system could be involved in compulsive behaviour in vulnerable populations.
authors.affiliation: Department of Psychology, University of Almería, CeiA3, Carretera de Sacramento s/n, 04120, Almería, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Merchán
authors.affiliation: Department of Psychology, University of Almería, CeiA3, Carretera de Sacramento s/n, 04120, Almería, Spain.
authors.forename: S V
authors.initials: SV
authors.lastname: Navarro
authors.affiliation: Department of Drug Design and Pharmacology, University of Copenhagen, 2100, Copenhagen, Denmark.
authors.forename: A B
authors.initials: AB
authors.lastname: Klein
authors.affiliation: Research Laboratory for Stereology and Neuroscience, Bispebjerg and Frederiksberg Hospitals, Copenhagen University Hospital, 2300, Copenhagen, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Aznar
authors.affiliation: Institute of Biomedical Research of Barcelona, IIBB-CSIC-IDIBAPS, CIBERESP (CS), CIBERSAM (LC), 08028, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Campa
authors.affiliation: Institute of Biomedical Research of Barcelona, IIBB-CSIC-IDIBAPS, CIBERESP (CS), CIBERSAM (LC), 08028, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Suñol
authors.affiliation: Department of Psychology, University of Almería, CeiA3, Carretera de Sacramento s/n, 04120, Almería, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Moreno
authors.affiliation: Department of Psychology, University of Almería, CeiA3, Carretera de Sacramento s/n, 04120, Almería, Spain. pflores@ual.es.
authors.forename: P
authors.initials: P
authors.lastname: Flores
mesh_terms: D000679:Amygdala / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003192:Compulsive Behavior / Q000378:metabolism*; D004032:Diet; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004326:Drinking / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D017072:Neostriatum / Q000378:metabolism; D059606:Polydipsia / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D014364:Tryptophan / Q000172:deficiency* / Q000378:metabolism
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D014364:Tryptophan; D004298:Dopamine
keywords: 5-HT2A binding; Chronic tryptophan depletion; Compulsivity; Inhibitory control; Monoamines; Schedule-induced polydipsia