Effects of tryptophan deficiency on prepulse inhibition of the acoustic startle in rats.
BACKGROUND
Serotonin (5-HT) plays a key role in the pathophysiology of psychotic disorders, presumably through a modulation of dopamine (DA) transmission. Reduction of 5-HT signaling has been suggested to enhance dopaminergic responses in animal models of psychosis. An intriguing naturalistic strategy to reduce 5-HT brain content is afforded by the dietary restriction to its precursor, l-tryptophan (TRP).


OBJECTIVE
We investigated the impact of a TRP-deficient diet in rats on the prepulse inhibition of the startle (PPI), a measure of sensorimotor gating which is typically impaired by psychotomimetic substances.


METHODS
After either short-term (6 h) or long-term (14 days) TRP deprivation, rats were tested for startle reflex and PPI. Moreover, we assessed the impact of both TRP deprivation regimens on PPI reduction induced by the psychotomimetic substance d-amphetamine (AMPH).


RESULTS
Both TRP-deficient regimens failed to significantly affect PPI responses. However, chronic, but not short-term, TRP-deficient diet induced a significant sensitization to the effects of AMPH (1.25-2.5 mg/kg, subcutaneous). The enhanced predisposition to PPI disruption elicited by prolonged TRP deprivation was completely reversed 24 h after reinstatement of TRP in the diet, as well as pretreatment with antipsychotic drugs haloperidol (0.1 mg/kg, intraperitoneal) and clozapine (5 mg/kg, intraperitoneal), which exert their therapeutic action mostly through blockade of DA D(2) receptors.


CONCLUSIONS
The present results confirm and extend previous findings on the impact of serotonergic signaling in the modulation of DA transmission in schizophrenia and point to chronic TRP deprivation as a potential model of environmental manipulation that may produce a sensitization to psychotic-like symptoms induced by dopaminergic activation.
Bortolato
Marco
M
Department of Neuroscience Bernard B. Brodie, University of Cagliari, Cittadella Universitaria, S.S.554 Km 4,500, 09042 Monserrato, CA, Italy. marco.bortolato@inwind.it
Frau
Roberto
R
Orrù
Marco
M
Collu
Maria
M
Mereu
Giampaolo
G
Carta
Manolo
M
Fadda
Fabio
F
Stancampiano
Roberto
R
D000161:Acoustic Stimulation; D000596:Amino Acids / Q000032:analysis / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D003627:Data Interpretation, Statistical; D004032:Diet; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004435:Eating; D005433:Flour / Q000032:analysis; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology*; D014364:Tryptophan / Q000172:deficiency*; D003313:Zea mays / Q000737:chemistry
D000596:Amino Acids; D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D014364:Tryptophan; D000661:Amphetamine; D003024:Clozapine; D006220:Haloperidol