Research report Effect of lesioning the suprachiasmatic nuclei on behavioral despair in rats O ¨ zgu ¨r Tatarog ˘lu 1 , Ayla Aksoy, Ajda Yılmaz 2 , Resit Canbeyli * Psychobiology Laboratory, Department of Psychology, Bog ˘azic ßi University, 80815, Bebek, Istanbul, Turkey Accepted 18 November 2003 Abstract The suprachiasmatic nucleus (SCN) is involved in regulating many biological rhythms. Several lines of research implicate the SCN in affective behavior. The SCN is directly involved in regulating the daily rhythms of the hypothalamo – pituitary –adrenal (HPA) axis hormones involved in stress. Bilateral lesions of the SCN disrupt both the rhythms and the basal levels of the HPA axis hormones involved in coping with stress. Moreover, stress can affect the biological rhythms regulated by the SCN, and disruption of biological rhythms in turn can cause stress. The present study assessed the effect of bilateral destruction of the SCN on behavioral despair, an animal model of depression sensitive to antidepressant treatment. The results indicate that bilateral destruction of the SCN results in reduced immobility in the second forced swimming test (FST) compared to sham controls and animals with incomplete lesions. These results indicate that bilateral destruction of the SCN has a protective effect in the induction of behavioral despair which may arise out of disruption of the secretion of the HPA axis hormones and/or of the neural connections between the SCN and the limbic structures that modulate the response to swim stress. D 2004 Elsevier B.V. All rights reserved. Theme: Neural basis of behavior Keywords: Stress Keywords: Suprachiasmatic nucleus; Forced swimming; Biological rhythms; Depression; Wistar rats 1. Introduction The suprachiasmatic nucleus (SCN) is the master pace- maker of the brain that regulates a large number of circadian and circannual rhythms [65]. While earlier stud- ies have emphasized the input and output organization of the pacemaker in regulating biorhythms, more recent studies have begun to discover a variety of roles for the SCN in cognitive [3,22,59] as well as affective functions and disorders [10,21,63]. A major impetus to investigate the role of the SCN in the regulation of affective behavior and psychopathology arose out of observations that light treatment—involving the major input by which the pace- maker is entrained—can alleviate the symptoms of Sea- sonal Affective Disorder (SAD) and some other forms of depression [24,46]. Studies have uncovered a reciprocal relationship between SCN function and stress-related behaviors in that while stress and psychopathology can disrupt biological rhythms [35,40,62], disruption of bio- logical rhythms by phase changes in SCN functioning can induce stress [34,56,57]. More recently, fear has been shown to interfere with light-induced phase changes in SCN functions indicating that SCN is affected by emo- tional states [1]. Conversely, SCN-regulated circadian rhythms can be altered by the emotional state of the animal [6,14,55]. Neuroanatomical studies have revealed extensive and usually reciprocal relationship between the SCN and several limbic structures that figure critically in affective behavior and psychopathology [11,38,65–68]. The neurochemical basis for the involvement of the SCN in affective behavior and possibly in psychopathology is likely to be related to its mediatory role in the regulation of the hypothalamo – pitu- itary–adrenal (HPA) axis response to stress [9,11,12,32,49]. 0006-8993/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2003.11.063 * Corresponding author. Tel.: +90-212-358-1540x2129; fax: +90-212- 287-2472. E-mail address: canbeyli@boun.edu.tr (R. Canbeyli). 1 Present address: University of Virginia, Charlotte, VA, USA. 2 Present address: The Royal Society of Science, Netherlands Institute for Brain Research, 1105 AZ Amsterdam, Netherlands. www.elsevier.com/locate/brainres Brain Research 1001 (2004) 118 – 124