| 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.
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| MeSH term(s) |
Acoustic Stimulation ; Animals ; Behavior, Animal/drug effects ; Brain/drug effects ; Brain/metabolism ; Dyskinesia, Drug-Induced/diet therapy ; Gait Disorders, Neurologic/chemically induced ; Gait Disorders, Neurologic/diet therapy ; Male ; Nerve Tissue Proteins/agonists ; Nerve Tissue Proteins/antagonists & inhibitors ; Nerve Tissue Proteins/metabolism ; Neural Inhibition/drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptor, Serotonin, 5-HT1A/chemistry ; Receptor, Serotonin, 5-HT1A/metabolism ; Receptors, Serotonin, 5-HT2/chemistry ; Receptors, Serotonin, 5-HT2/metabolism ; Reflex, Startle/drug effects ; Sensory Gating/drug effects ; Serotonergic Neurons/drug effects ; Serotonergic Neurons/metabolism ; Serotonin 5-HT1 Receptor Agonists/toxicity ; Serotonin 5-HT1 Receptor Antagonists/pharmacology ; Serotonin 5-HT2 Receptor Agonists/toxicity ; Tryptophan/antagonists & inhibitors ; Tryptophan/deficiency |
| Chemical Substances |
Nerve Tissue Proteins ; Receptors, Serotonin, 5-HT2 ; Serotonin 5-HT1 Receptor Agonists ; Serotonin 5-HT1 Receptor Antagonists ; Serotonin 5-HT2 Receptor Agonists ; Receptor, Serotonin, 5-HT1A (112692-38-3) ; Tryptophan (8DUH1N11BX) |
| Language |
English |
| Publishing date |
2012-11-06 |
| Publishing country |
Netherlands |
| Document type |
Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID |
1082947-7 |
| ISSN |
1873-7862 ; 0924-977X |
| ISSN (online) |
1873-7862 |
| ISSN |
0924-977X |
| DOI |
10.1016/j.euroneuro.2012.10.009 |
| Database |
MEDical Literature Analysis and Retrieval System OnLINE |
