Printed in the U.S.A. Pergamon Journals

Supersensitivity of a muscarinic mechanism is implicated in the pathophysiology of depression. Bright artificial light is efficacious in the treatment of Seasonal Affective Disorder (SAD). We studied the effect of constant bright light (11,500 lux) on the sensitivity of adult, male rats to oxotremorine, 1.5 mg/kg ip, using a repeated measures design. Oxotremorine challenges were proceeded by the injection of methylscopolamine, 1 mg/kg ip, by 70 minutes. Temperature was telemetrically measured every 10 minutes for 120 minutes starting 10 minutes after the injection of oxotremorine. Prior to and after 7 continuous days of exposure to bright light, the sample exhibited a hypothermic response of 2.50 + 0.4R"C (mean + SEM) and 0.29 + 0.31"C (mean + SEM), respectively-(p < 0.0014). _ All 7 animals exhibited blunting to the thermic response to oxotremorine. Bright light also blocked the capacity of amitriptyline to supersensitize a central muscarinic mechanism. Exposure to light at an intensity of 300 lux for 7 days had no effect on the thermic response to oxotremorine. These data are consistent with the hypotheses that the biology of depression involves supersensitivity of central muscarinic mechanisms and that the effects of bright artificial light are not the consequence of shifting circadian rhythms. Seasonal Affective Disorder (SAD) is a syndrome characterized by recurrent depressions which occur annually (1). This syndrome responds to daily treatment with 2-6 hours of bright artificial light (l-5). A mechanism accounting for the efficacy of this treatment has not been identified. Certain forms of affective disorders may involve state independent supersensitivity of central cholinergic systems (6). Data supporting a cholinergic hypothesis of depression were recently summarized (7-8). This article presents data indicating that bright artificial light blunts the hypothermic response to oxotremorine and prevents the supersensitization of muscarinic mechanisms produced by a muscarinic receptor antagonist (9)