[Abstract Title]. - Society for Neuroscience

Title: Rapid modulation of TRH and TRH-like peptide levels in rat brain and peripheral tissues
by prazosin
Authors: *A. E. PEKARY 1,3 , A. SATTIN 2 , J. BLOOD 1 ;
1 Res., 2 Psychiatry, VA Greater Los Angeles Hlthcare Syst, Los Angeles, CA; 3 Med., UCLA, Los
Angeles, CA
Abstract: Hyperresponsiveness to norepinephrine contributes to post-traumatic stress disorder
(PTSD). Prazosin, a brain-active α1-adreoreceptor blocker originally used for the treatment of
hypertension has recently been reported to alleviate trauma nightmares, sleep disturbance and
improve global clinical status in war veterans with PTSD. In rats it reduces the acoustic startle
response following an inescapable stressor. Compelling evidence of a role for thyrotropinreleasing
hormone (TRH, pGlu-His-Pro-NH2) in the pathophysiology and treatment of
neuropsychiatric disorders such as major depression, and PTSD has recently been reported.
Mutation of the TRH type I receptor in mice results in behavioral responses consistent with panic
disorder and major depression (Zeng et al., 2007). To determine whether TRH or TRH-like
peptides (pGlu-X-Pro-NH2, where “X” can be any amino acid residue) mediate the therapeutic
effects of prazosin, young adult, male Lewis and Sprague-Dawley (SD) rats were injected ip with
4 mg/kg prazosin and peptide levels in brain and peripheral tissues were measured 0, 2, 4 and 6 h
later. Changes in peptide levels at 2 h are most like due to altered release and clearance since
peptide synthesis and posttranslational processing take more time. Among the 11 brain regions:
pyriform cortex (PYR), entorhinal cortex (ENT), cerebellum (CBL), nucleus accumbens (NA),
frontal cortex (FCX), amygdala (AY), posterior cingulate (PCNG), striatum (STR), hippocampus
(HC), medulla oblongata (MED) and anterior cingulate (ACNG) and 8 peptides measured there
were 10 significant changes in SD and 6 in Lewis rats at 2 h when compared to the
corresponding control peptide levels. For the 5 peripheral tissues (adrenals, testes, epididymides,
pancreas and prostate), there were 13 significant changes in SD and 13 in Lewis rats. Responses
for a given peptide and brain region were correlated between SD and Lewis rats. The number of
significant within-brain correlations (given in parentheses) were: PYR (7), ENT (6), FCX (5),
CBL (5), NA (3), AY (3), PCNG (2), STR (2), HC (1), MED (1), ACNG (0). The corresponding
list for peripheral tissues was: adrenal (5), prostate (5), pancreas (3), testes (3) and epididymides
(2). The extent of prazosin effects on TRH and TRH-like peptide levels in a given brain region or
peripheral tissue correlates with the local levels of norepinephrine and α1-adrenoreceptors,
suggesting that these peptides may play a role in the therapeutic effects of this brain-active drug.
Disclosures: A.E. Pekary, VA Greater Los Angeles Healthcare System, A. Employment (full
or part-time); VA Merit (AEP & AS), B. Research Grant (principal investigator, collaborator or
consultant and pending grants as well as grants already received); A. Sattin, VA Merit, B.
Research Grant (principal investigator, collaborator or consultant and pending grants as well as
grants already received); J. Blood, None.
Poster