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

• Published in: Psychopharmacology Vol. 234; no. 8; pp. 1223 - 1236
• Main Authors: Merchán, A., Navarro, S. V., Klein, A. B., Aznar, S., Campa, L., Suñol, C., Moreno, M., Flores, P.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-04-2017; Springer; Springer Nature B.V
• Subjects: Amino acids; Amygdala - metabolism; Analysis of Variance; Animal behavior; Animals; Behavior, Animal - physiology; Biomedical and Life Sciences; Biomedicine; Brain - drug effects; Brain - metabolism; Compulsive behavior; Compulsive Behavior - metabolism; Diet; Disease Models, Animal; Dopamine - metabolism; Drinking - drug effects; Hippocampus - metabolism; Male; Mental disorders; Neostriatum - metabolism; Neurological research; Neurosciences; Original Investigation; Pharmacology/Toxicology; Physiological aspects; Polydipsia - metabolism; Psychiatry; Psychopharmacology; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT1A - metabolism; Receptor, Serotonin, 5-HT2A - metabolism; Rodents; Serotonin; Serotonin - metabolism; Synaptic transmission; Tryptophan; Tryptophan - deficiency; Tryptophan - metabolism; Compulsivity; Inhibitory control; Chronic tryptophan depletion; binding; 5-HT; Monoamines; Schedule-induced polydipsia; 5-HT2A binding
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-017-4561-5

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-HT
2A
and 5-HT
1A
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.