title: Chronic tryptophan deprivation attenuates gating deficits induced by 5-HT(1A), but not 5-HT₂ receptor activation.
abstract: The neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) exerts a multifaceted function in the modulation of information processing, through the activation of multiple receptor families. In particular, stimulation of 5-HT(1A) and 5-HT(2A) receptors leads to sensorimotor gating impairments and perceptual perturbations. Previous evidence has shown that chronic deprivation of L-tryptophan (TRP), the precursor of 5-HT, results in marked reductions of 5-HT brain levels, as well as neuroplastic alterations in 5-HT(1A) and 5-HT(2A) expression and/or signaling. Building on these premises, in the present study we tested whether a prolonged TRP deprivation may differentially impact the roles of these receptors in the regulation of the prepulse inhibition (PPI) of the acoustic startle reflex, a dependable index of gating. Male Sprague-Dawley rats were fed for 14 days with either a regimen with negligible TRP content (TR-) or the same diet supplemented of TRP (TR+). At the end of this schedule, rats were treated with the prototypical 5-HT(1A) receptor agonist 8-OH-DPAT (62.5-250 μg/kg, subcutaneous, s.c.) or the 5-HT₂ receptor agonist DOI (0.25-1 mg/kg, s.c.). Notably, the PPI deficits induced by 8-OH-DPAT in TR- rats were significantly milder than those observed in their TR+ counterparts; these effects were fully prevented by the 5-HT(1A) antagonist WAY-100135 (10 mg/kg, intraperitoneal). Conversely, TRP deprivation did not affect the PPI-disrupting properties of DOI. These findings suggest that prolonged 5-HT depletion attenuates the influence of 5-HT(1A), but not 5-HT₂ receptors on sensorimotor gating, confirming the distinct mechanisms of these two targets in PPI regulation.
authors.affiliation: Department of Biomedical Sciences, Division of Physiology; University of Cagliari, Cagliari, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Stancampiano
authors.forename: Roberto
authors.initials: R
authors.lastname: Frau
authors.forename: Valentina
authors.initials: V
authors.lastname: Bini
authors.forename: Maria
authors.initials: M
authors.lastname: Collu
authors.forename: Manolo
authors.initials: M
authors.lastname: Carta
authors.forename: Fabio
authors.initials: F
authors.lastname: Fadda
authors.forename: Marco
authors.initials: M
authors.lastname: Bortolato
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004409:Dyskinesia, Drug-Induced / Q000178:diet therapy*; D020233:Gait Disorders, Neurologic / Q000139:chemically induced / Q000178:diet therapy*; D008297:Male; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000737:chemistry / Q000378:metabolism*; D044348:Receptors, Serotonin, 5-HT2 / Q000737:chemistry / Q000378:metabolism; D013216:Reflex, Startle / Q000187:drug effects; D055139:Sensory Gating / Q000187:drug effects*; D059326:Serotonergic Neurons / Q000187:drug effects* / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists / Q000633:toxicity*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D058826:Serotonin 5-HT2 Receptor Agonists / Q000633:toxicity; D014364:Tryptophan / Q000037:antagonists & inhibitors / Q000172:deficiency*
chemical_list: D009419:Nerve Tissue Proteins; D044348:Receptors, Serotonin, 5-HT2; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D058826:Serotonin 5-HT2 Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D014364:Tryptophan
keywords: 5-HT(1A); 5-HT(2); Prepulse inhibition; Serotonin; Startle; Tryptophan