Evidence that corticotropin-releasing factor within the extended amygdala mediates the activation of tryptophan hydroxylase produced by sound stress in the rat.
Non-endocrine corticotropin-releasing factor (CRF) is believed to be involved in mediating stress behaviors in rats. The present study investigated the role of CRF in mediating the activation of tryptophan hydroxylase, the rate-limiting enzyme in serotonin synthesis, produced in response to sound stress. Bilateral injections of 0.5-3.0 micrograms of CRF directed towards the central nucleus of the amygdala increased tryptophan hydroxylase activity measured ex vivo when compared to vehicle-injected controls. This increase in enzyme activity, like that due to sound stress, was reversed in vitro by alkaline phosphatase. Intra-amygdala CRF (0.5 microgram) also enhanced the in vivo accumulation of 5-hydroxytryptophan (5-HTP) following the administration of m-hydroxylbenzylamine (NSD-1015, 200 mg/kg). The activation of tryptophan hydroxylase, produced by intra-amygdala CRF, was blocked by the CRF receptor antagonist alpha-helical CRF9-41 (10 micrograms). Additionally, the 5-HT1A agonist, gepirone, given either systemically (10 mg/kg) or intracerebrally into the region of the dorsal raphe (14 micrograms), blocked the tryptophan hydroxylase response to CRF. CRF did not increase tissue levels of 5-hydroxyindole acetic acid (5-HIAA) or the ratio of 5-HIAA to serotonin (5-HT) within the striatum of the same animals in which tryptophan hydroxylase activity was quantified, an effect produced by sound stress. Thus, while intra-amygdala CRF failed to mimic the sound stress response in its entirety, these data suggest that CRF is involved in mediating the activation of tryptophan hydroxylase produced by sound stress within the midbrain serotonin neurons.
Boadle-Biber
M C
MC
Department of Physiology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0551.
Singh
V B
VB
Corley
K C
KC
Phan
T H
TH
Dilts
R P
RP
D000161:Acoustic Stimulation; D000679:Amygdala / Q000502:physiology*; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D004789:Enzyme Activation; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D011903:Raphe Nuclei / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D013312:Stress, Physiological / Q000201:enzymology*; D014365:Tryptophan Hydroxylase / Q000378:metabolism*
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D003346:Corticotropin-Releasing Hormone; D014365:Tryptophan Hydroxylase