Neurotensin inhibits the activation of midbrain serotonergic neurons produced by random inescapable sound.
Previous studies indicate that exposure of rats to randomly presented, inescapable loud sound, referred to as sound stress, increases central serotonin turnover as well as the ex vivo activity of tryptophan hydroxylase (EC 1.14.16.4), the rate-limiting enzyme in serotonin biosynthesis. The purpose of this investigation was to determine whether intracerebroventricular (i.c.v.) administration of neurotensin (NT), a tridecapeptide found within the midbrain raphe, influences the activation of the midbrain serotonergic neurons by sound stress. Accumulation of 5-hydroxytryptophan (5-HTP) in vivo, in the presence of the aromatic amino acid decarboxylase inhibitor, NSD 1015 (m-hydroxybenzylhydrazine, 100 mg/kg i.p.) given immediately before a 30 min sound stress, was used as an index of in vivo tryptophan hydroxylase activity. Sound-stressed rats had significantly higher levels of 5-HTP in cortex and midbrain compared to sham-stressed controls. NT (0.01-3.3 nmol total), given i.c.v., 5 min prior to 30 min sound stress, completely blocked the enhanced accumulation of 5-HTP, but had no effect on basal accumulation of 5-HTP, except at the highest doses of 1.0 or 3.3 nmol, which others have previously shown to inhibit basal serotonergic metabolism. NT (0.3 and 3.3 nmol) blocked the increase in cortical tryptophan hydroxylase activity, ex vivo, in response to 30 min sound stress, without affecting basal enzyme activity. These and other recent data suggest a possible role for endogenous NT in the regulation of serotonergic neuronal activity within the midbrain raphe.
Dilts
R P
RP
Department of Physiology, School of Medicine, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0551, USA.
Novitzki
M R
MR
Phan
T H
TH
Corley
K C
KC
Boadle-Biber
M C
MC
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D008297:Male; D008636:Mesencephalon / Q000187:drug effects*; D009496:Neurotensin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D013016:Sound; D013312:Stress, Physiological / Q000378:metabolism*
D012701:Serotonin; D009496:Neurotensin; D006916:5-Hydroxytryptophan