Alprazolam treatment immediately after stress exposure interferes with the normal HPA-stress response and increases vulnerability to subsequent stress in an animal model of PTSD.
BACKGROUND
In light of clinical reports suggesting that early benzodiazepine administration interferes with long-term recovery from traumatic stress, a prospective animal model for PTSD was employed to assess the short- and long-term effects of a brief course of alprazolam following stress exposure.


METHODS
Animals exposed to stress were treated either 1 h or 7 days later with alprazolam or vehicle for 3-days. Outcome measures included behavior in the elevated plus-maze (EPM) and acoustic startle response (ASR) tests 30 days after initial exposure and freezing behavior upon exposure to a trauma-cue on day 31. One group was repeatedly exposed to the triggering trauma shortly before and after treatment and assessed as above. Circulating corticosterone levels were assessed 4 h after initiation of alprazolam and post-treatment. Pre-set cut-off behavioral criteria classified exposed animals according to their EPM and ASR response-patterns into 'extreme', 'minimal,' or 'partial' behavioral response for analysis of prevalence rates.


RESULTS
Immediate alprazolam treatment was effective in alleviating anxiety at day 4. No observable anxiolytic effects remained at day 30. Immediate alprazolam also resulted in significantly greater freezing response to trauma-cue exposure and in extreme responses to double-exposure. Corticosterone levels were significantly suppressed by alprazolam during treatment and rebounded after cessation.


CONCLUSIONS
A brief course of alprazolam in the immediate aftermath of stress-exposure is associated with less favorable responses to additional stress-exposure later on. Alprazolam was associated with a significant attenuation of the HPA-response, suggesting a possible link between initial HPA-axis response disruption and the subsequent unfavorable outcomes.
Matar
Michael A
MA
Ministry of Health Mental Health Center, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Zohar
Joseph
J
Kaplan
Zeev
Z
Cohen
Hagit
H
D000161:Acoustic Stimulation / Q000009:adverse effects; D000525:Alprazolam / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage*; D001522:Behavior, Animal / Q000187:drug effects; D003345:Corticosterone / Q000097:blood*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013216:Reflex, Startle / Q000187:drug effects; D012720:Severity of Illness Index; D013313:Stress Disorders, Post-Traumatic / Q000097:blood* / Q000188:drug therapy*; D013997:Time Factors
D014151:Anti-Anxiety Agents; D003345:Corticosterone; D000525:Alprazolam