Effect of gepirone on increases in tryptophan hydroxylase in response to sound stress.
Pretreatment (15 min) of male rats with gepirone given parenterally (10 mg/kg i.p.) or intracranially into the dorsal raphe nucleus (14 or 21 micrograms) blocks the rapidly reversible increase in brain tryptophan hydroxylase activity and 5-hydroxyindolamine acetic acid tissue levels seen in vitro after 1-h acute sound stress. Chronic gepirone treatment over 28 days (40 mg/day s.c.) prevents the stable enzyme activity increase induced by repeated sessions of sound stress, and the rapidly reversible increase always observed following sound stress. The gepirone metabolite, 1-(2-pyrimidinyl)-1-piperazine, is inactive in each of these experiments. Transient blood pressure elevations occur with each sound presentation, but no persistent hypertension is observed with repeated sound-stress exposures. Gepirone may block the sound stress-induced biochemical increases by its inhibition of serotonergic neuronal firing in the dorsal raphe nucleus that is mediated by its agonist action at the somatodendritic (5-HT1A) autoreceptors.
Corley
K C
KC
Department of Physiology, Virginia Commonwealth University, Richmond 23298.
Singh
V B
VB
Phan
T H
TH
Boadle-Biber
M C
MC
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004334:Drug Administration Schedule; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D011743:Pyrimidines / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012701:Serotonin / Q000378:metabolism / Q000502:physiology; D013016:Sound / Q000009:adverse effects*; D013312:Stress, Physiological / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology; D013997:Time Factors; D014365:Tryptophan Hydroxylase / Q000187:drug effects* / Q000378:metabolism
D014151:Anti-Anxiety Agents; D011743:Pyrimidines; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014365:Tryptophan Hydroxylase; C039979:gepirone