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Integrative physiology of antidepressant drug action
Author(s) -
Lowry Christopher Alan,
Hale Matthew William,
Dady Kathleen Francis,
Lukkes Jodi L,
Kelly Kyle John,
Raison Charles L
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1079.8
Subject(s) - citalopram , antidepressant , behavioural despair test , pharmacology , reuptake inhibitor , hyperthermia , serotonin , drug , medicine , psychology , receptor , hippocampus
Previous studies have demonstrated that depressed patients have dysfunction of thermoregulatory cooling, while antidepressants of diverse pharmacological profiles induce sweating as a clinical side effect, suggesting that the pathophysiology of depression as well as antidepressant drug action may involve interactions with thermoregulatory pathways. To test this hypothesis, we investigated interactions between acute whole body warming and treatment with the selective serotonin reuptake inhibitor, citalopram, on body temperature, measured using chronically implanted telemetric recording devices, and antidepressant‐like behavior in the forced swim test in rats. Using a subthreshold dose of citalopram, we found that citalopram, by itself, induced hyperthermia that was comparable to that induced by exposure to increased ambient temperature (37 degrees C) for 85 min. Neither citalopram by itself, nor exposure to increased ambient temperature induced antidepressant‐like effects in the forced swim test. However, when rats were both treated with citalopram and exposed to elevated ambient temperature, rats experienced an exaggerated hyperthermia that was highly correlated with antidepressant‐like behavioral responses. These data provide a rationale for novel therapeutic strategies for the treatment of affective disorders, including development of novel antidepressant drugs.