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 i nvolved in mediating stress behaviors in rats. The present study inves tigated the role of CRF in mediating the activation of tryptophan hydr oxylase, the rate-limiting enzyme in serotonin synthesis, produced in response to sound stress. Bilateral injections of 0.5-3.0 mug of CRF d irected towards the central nucleus of the amygdala increased tryptoph an hydroxylase activity measured ex vivo when compared to vehicle-inje cted controls. This increase in enzyme activity, like that due to soun d stress. was reversed in vitro by alkaline phosphatase. Intra-amygdal a CRF (0.5 mug) also enhanced the in vivo accumulation of 5-hydroxytry ptophan (5-HTP) following the administration of m-hydroxylbenzylamine (NSD-1015, 200 mg/kg). The activation of tryptophan hydroxylase. produ ced hy intra-amygdala CRF, was blocked by the CRF receptor antagonist alpha-helical CRF9-41 (10 mug). Additionally, the 5-HT1A agonist, gepi rone, given either systemically (10 mg/kg) or intracerebrally into the region of the dorsal raphe (14 mug), blocked the tryptophan hydroxyla se response to CRF. CRF did not increase tissue levels of 5-hydroxyind ole acetic acid (5-HIAA) or the ratio of 5-HIAA to serotonin (5-HT) wi thin the striatum of the same animals in which tryptophan hydroxylase activity was quantified, an effect produced by sound stress. Thus, whi le intra-amygdala CRF failed to mimic the sound stress response in its entirety, these data suggest that CRF is involved in mediating the ac tivation of tryptophan hydroxylase produced by sound stress within the midbrain serotonin neurons.