Pharmacological evaluation of the stress-induced social avoidance model of anxiety.
We have shown earlier that mild electric shocks induce a lasting social avoidance in male rats. Here we investigated whether shock-induced social avoidance can be developed into a laboratory model of stress-induced anxiety. The putative new model would assess sub-chronic, stress-induced anxiety (as opposed to tests based on natural fear) in a heterologous context (as opposed to classical fear conditioning). A single exposure to mild electric shocks induced a robust social avoidance that lasted more than 5 days. Low doses of chlordiazepoxide (0.5, 1 mg/kg), diazepam (0.5, 1, 5 mg/kg), buspirone (0.3, 1 mg/kg), and fluoxetine (1, 3, 5 mg/kg) abolished this effect, whereas the anxiogenic compound m-chlorophenylpiperazine (0.5-3 mg/kg) induced social avoidance in unshocked rats. These effects were produced at doses that did not affect locomotion in the open field. Haloperidol (0.05, 0.1, 1, 5 mg/kg) influenced social avoidance at sedative doses only. The sensitivity of the model to anxiolytic agents was compromised at high (sedating) doses. Taken conjointly, these data show that shock-induced social avoidance can be used to assess the anxiolytic potential of compounds. In addition to predictive validity, the model appears to show construct and face validity as well: stress is among the etiological factors of, whereas social avoidance simulates the social deficits seen in, a variety of anxiety disorders. The model may be used to study the effects of anxiolytics on sub-chronic states of stress-induced anxiety.
Leveleki
Cs
C
EGIS Pharmaceuticals, Budapest, Hungary.
Sziray
N
N
Levay
G
G
Barsvári
B
B
Soproni
K
K
Mikics
E
E
Haller
J
J
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001008:Anxiety Disorders / Q000503:physiopathology*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D002065:Buspirone / Q000494:pharmacology; D002707:Chlordiazepoxide / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000009:adverse effects; D005473:Fluoxetine / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008959:Models, Neurological; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010698:Phobic Disorders / Q000503:physiopathology*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013315:Stress, Psychological / Q000503:physiopathology*
D014151:Anti-Anxiety Agents; D010879:Piperazines; D017366:Serotonin Receptor Agonists; D005473:Fluoxetine; D002707:Chlordiazepoxide; D006220:Haloperidol; D003975:Diazepam; C015068:1-(3-chlorophenyl)piperazine; D002065:Buspirone