Inhibitory effects of antipsychotic and anxiolytic agents on stress-induced degranulation of mouse dermal mast cells.
BACKGROUND
Various psychological stresses induce degranulation of mast cells. It has been confirmed by animal experiments that stress induced by restraint promotes mast-cell degranulation in various organs, and that the degranulation is inhibited by pretreatment with corticotropin-releasing factor (CRF)-neutralizing antibodies, CRF receptor antagonists, and neurotensin (NT) antagonists. Previous studies have suggested that anxiety and fear induced in animals by psychological stressors promote the production and release of various neuropeptides and neurotransmitters, and induce degranulation of mast cells in several organs.


OBJECTIVE
To evaluate the effect of prior treatment with antipsychotic and anxiolytic agents to inhibit foot-shock (FS) stress-induced degranulation of mouse dermal mast cells.


METHODS
Using a communication box system, FS was administered to mice and the degranulated dermal mast cells were counted. Chlorpromazine (2 or 4 mg/kg body weight), tandospirone (10 mg/kg body weight) or CRA1000, a selective non-peptidic CRF receptor type 1 antagonist (10 or 100 mg/kg body weight) was injected intraperitoneally 1 h before exposure to FS.


RESULTS
After FS was administered, the number of dermal mast cells did not change. However, FS significantly increased the proportion of degranulated mast cells. Pretreatment of mice with chlorpromazine hydrochloride, an antipsychotic agent (2 or 4 mg/kg), or the anxiolytic agents tandospirone citrate (10 mg/kg) or CRA1000 (10 or 100 mg/kg), significantly inhibited the FS-induced mast-cell degranulation (P < 0.05, P < 0.01, P < 0.05, P < 0.05, and P < 0.05, respectively).


CONCLUSIONS
Antipsychotic and anxiolytic agents may be effective treatments for stress-aggravated inflammatory skin diseases by inhibition of mast-cell degranulation.
Shimoda
T
T
Department of Dermatology, Nippon Medical School, Tokyo, Japan. takako@nms.ac.jp
Liang
Z
Z
Suzuki
H
H
Kawana
S
S
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D015550:Cell Degranulation / Q000187:drug effects*; D002746:Chlorpromazine / Q000494:pharmacology; D005260:Female; D054833:Isoindoles / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D013315:Stress, Psychological
D014151:Anti-Anxiety Agents; D014150:Antipsychotic Agents; D054833:Isoindoles; D010879:Piperazines; D011725:Pyridines; D011743:Pyrimidines; C055267:tandospirone; C117406:CRA1000; D002746:Chlorpromazine