Acoustic stimulation in vivo and corticotropin-releasing factor in vitro increase tryptophan hydroxylase activity in the rat caudal dorsal raphe nucleus.
Exposure of rats to unpredictable loud sound pulses increases activity of the rate-limiting enzyme for serotonin synthesis, tryptophan hydroxylase (TPH), in the median raphe nucleus (MnR) and a mesolimbocortical serotonergic system. Corticotropin-releasing factor (CRF)-induced activation of a subset of serotonergic neurons in the caudal dorsal raphe nucleus (DR) may underlie stress-related increases in TPH activity in the MnR and a mesolimbocortical serotonergic system. An in vivo acoustic stimulation paradigm and an in vitro brain slice preparation were designed to test the hypothesis that stress-related stimuli and CRF receptor activation have convergent actions on TPH activity in the caudal DR (DRC). We measured 5-hydroxytryptophan (5-HTP) accumulation as an index of TPH activity following inhibition of aromatic amino acid decarboxylase (using NSD-1015). To examine effects of acoustic stimulation on TPH activity, male Wistar rats, pretreated with NSD-1015, were exposed to a 30 min sham, predictable or unpredictable acoustic stimulation paradigm; brains were frozen and microdissected for analyses of tissue 5-HTP concentrations in subregions of the DR. To examine the effect of CRF receptor activation on TPH activity, freshly prepared brain slices were exposed to CRF (0-2000 nM) for 10 min in the presence of NSD-1015, then frozen and microdissected for analysis of tissue 5-HTP concentrations. Increases in TPH activity in the DRC, but not other subregions, were observed in both paradigms. These findings are consistent with the hypothesis that stress-related increases in TPH activity are mediated via effects of CRF or CRF-related neuropeptides on a mesolimbocortical serotonergic system originating in the DRC.
Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA. andrew.k.evans@colorado.edu
Andrew K
AK
Evans
Jasper L T
JL
Heerkens
Christopher A
CA
Lowry
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000161:Acoustic Stimulation; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology / Q000502:physiology*; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D011903:Raphe Nuclei / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists; D013315:Stress, Psychological / Q000201:enzymology* / Q000209:etiology; D014365:Tryptophan Hydroxylase / Q000378:metabolism*
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D006834:Hydrazines; D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone; C004297:3-hydroxybenzylhydrazine; D006916:5-Hydroxytryptophan; D014365:Tryptophan Hydroxylase