Female mammals have long been neglected in biomedical research. The NIH mandated enrollment of women in human clinical trials in 1993, but no similar initiatives exist to foster research on female animals. We reviewed sex bias in research on mammals in 10 biological fields for 2009 and their historical precedents. Male bias was evident in 8 disciplines and most prominent in neuroscience, with single-sex studies of male animals outnumbering those of females 5.5 to 1. In the past half-century, male bias in non-human studies has increased while declining in human studies. Studies of both sexes frequently fail to analyze results by sex. Underrepresentation of females in animal models of disease is also commonplace, and our understanding of female biology is compromised by these deficiencies. The majority of articles in several journals are conducted on rats and mice to the exclusion of other useful animal models. The belief that non-human female mammals are intrinsically more variable than males and too troublesome for routine inclusion in research protocols is without foundation. We recommend that when only one sex is studied, this should be indicated in article titles, and that funding agencies favor proposals that investigate both sexes and analyze data by sex.

Bilateral electrolytic lesions in the suprachiasmatic nuclei permanently eliminated nocturnal and circadian rhythms in drinking behavior and locomotor activity of albino rats. The generation of 24-hr behavioral rhythms and the entrainment of these rhythms to the light-dark cycle of environmental illumination may be coordinated by neurons in the suprachiasmatic region of the rat brain. Destruction of the medial preoptic area had no effect on 24-hr drinking rhythms.The widespread occurrence and biological significance of 24-hr rhythms has been extensively documented (1, 2). Although rhythmic variations in animal behavior and physiology are ordinarily synchronized with fluctuations in light and temperature (1), many rhythms persist in free-running form with periods of about 24 hr (circadian rhythms) in the absence of all obvious entraining stimuli. Such demonstrations are generally interpreted as reflecting the operation of a biological clock within the animal (1).The identification of the neural substrate responsible for the 24-hr behavioral rhythms of mammals has yet to be accomplished (3,4). Circadian rhythms have been remarkably resistant to many forms of interference with the nervous system, including such radical treatments as anoxia, convulsions, poisoning, anesthesia, and acute stress (4). Some loss of rhythmicity in eating, but not in drinking, behavior of rats occurs after lesions are placed in the region of the ventromedial hypothalamus (5). However, these lesions also interfere with the homeostatic control of eating and body weight, and it is difficult to assess their effects on the biological clock per se.Several circadian neuroendocrine rhythms have been eliminated by lesions or surgical isolation of the anterior hypothalamus from the medial basal hypothalamus (6). In addition, recent anatomical studies have once again raised the possibility of direct visual input to the anterior hypothalamus via retino-hypothalamic pathways terminating in the suprachiasmatic nuclei and arcuate region (7,8). These considerations, and our previous failure to disrupt nocturnal drinking rhythms with lesions that interrupted the primary and accessory visual pathways (9), suggested to us that the suprachiasmatic region might be involved in the generation and entrainment of behavioral rhythms.In the present experiment we attempted to interfere with circadian drinking and activity rhythms of rats by selectively damaging several regions of the hypothalamus.Abbreviations: LD, light-dark cycle; SCN, suprachiasmatic nucleus; MPO, medial preoptic nucleus. METHODSAdult ovariectomized Sprague-Dawley rats were housed individually in cages with free access to food and water. The experimental room was illuminated by fluorescent lights providing cool white light; the average intensity of illumination at the face of the cage was 6 ft-c. The light-dark cycle (L-D) consisted of alternating 12-hr periods of light and darkness; the dark period began at 9 p.m. At various times animals were maintained on a reversed I-D cycle (the dail...

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