TY - JOUR

T1 - Tryptophan depletion affects compulsive behaviour in rats

T2 - strain dependent effects and associated neuromechanisms

AU - Merchán, A

AU - Navarro, S V

AU - Klein, A B

AU - Aznar, S

AU - Campa, L

AU - Suñol, C

AU - Moreno, M

AU - Flores, P

PY - 2017/4

Y1 - 2017/4

N2 - RATIONALE: 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.OBJECTIVES: 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-HT2A and 5-HT1A receptor binding, in different brain regions.METHODS: 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.CONCLUSIONS: These results suggest that alterations of the serotonergic system could be involved in compulsive behaviour in vulnerable populations.

AB - RATIONALE: 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.OBJECTIVES: 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-HT2A and 5-HT1A receptor binding, in different brain regions.METHODS: 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.CONCLUSIONS: These results suggest that alterations of the serotonergic system could be involved in compulsive behaviour in vulnerable populations.

KW - Amygdala

KW - Analysis of Variance

KW - Animals

KW - Behavior, Animal

KW - Brain

KW - Compulsive Behavior

KW - Diet

KW - Disease Models, Animal

KW - Dopamine

KW - Drinking

KW - Hippocampus

KW - Male

KW - Neostriatum

KW - Polydipsia

KW - Rats

KW - Rats, Wistar

KW - Receptor, Serotonin, 5-HT1A

KW - Receptor, Serotonin, 5-HT2A

KW - Serotonin

KW - Tryptophan

KW - Journal Article

U2 - 10.1007/s00213-017-4561-5

DO - 10.1007/s00213-017-4561-5

M3 - Journal article

C2 - 28280881

VL - 234

SP - 1223

EP - 1236

JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

IS - 8

ER -