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Serotonin and Stress: Protective or Malevolent Actions in the Biobehavioral Response to Repeated Trauma?
Author(s) -
HARVEY BRIAN H.,
NACITI CARLA,
BRAND LINDA,
STEIN DAN J.
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1314.035
Subject(s) - serotonin , medicine , psychology , fight or flight response , chemistry , receptor , biochemistry , gene
A bstract : Structural hippocampus and prefrontal cortex changes occur in patients with posttraumatic stress disorder (PTSD) that appears correlated with cognitive dysfunction. In these brain regions, serotonin (5HT) plays a prominent role in symptom presentation and treatment of PTSD. However, 5HT is both anxiogenic and anxiolytic, and while 5HT reuptake inhibitors are effective in treatment, the role of 5HT in the development of PTSD remains uncertain. Using a model of repeated trauma in rats, we observed significant spatial memory impairment together with significantly increased 5HT 1A receptor density (B max ), decreased 5HT 1A receptor affinity (K d ), and significantly increased 5HT 2A receptor affinity on day 7 poststress. The serotonergic agent fluoxetine (FLX; 10 mg/kg/d ip) administered 1 week before stress and continuing throughout the stress procedure, but not the 5HT depleter p ‐chloro‐phenylalanine (PCPA; 300/100/50mg/kg/d ip), prevented stress‐induced cognitive dysfunction. PCPA, however, reversed stress‐induced hippocampal 5HT 1A receptor affinity changes, with FLX narrowly missing significance. Neither drug reversed stress effects on 5HT 2A receptor affinity. Thus, 5HT plays an important part in the cognitive‐behavioral changes evoked by repeated trauma. That raised 5HT activity may mediate hippocampal 5HT 1A receptor changes evoked by stress suggests a bidirectional role for 5HT in the development of PTSD.