al. studied the levels of dynorphin during periods of food restriction. the group found that while food did not alter the expression of dynorphin b, it increases dynorphin a levels in several rat brain regions (hypothalamus, nucleus accumbens, and bed nucleus of the stria terminalis). recent research on dynorphin knockout mice did not find differences between knockout and control animals in food intake, but found that fat storage was reduced in male knockout mice. fatty acids were oxidized more quickly in knockout animals. studies have also shown that ingesting a high-fat diet increases the gene expression of dynorphin in the hypothalamus. thus, dynorphin may cause overeating when a high-fat diet is available. morley & levine were the first to describe the role of opioid peptides in stress-related eating. in their study, mice had their tails pinched (causes stress), which induced eating. stress-related eating was reduced by injecting naloxone, an opioid peptide antagonist. mandenoff et al. proposed that, although endogenous opioids are not necessary to maintain body weight and energy expenditure under predictable circumstances, they become activated under stressful conditions. they found that endogenous opioids, such as dynorphin, stimulate appetite and decrease energy expenditure. taken together, the studies above suggest an important evolutionary mechanism in which more food is eaten, more nutrients are stored, and less energy is expended by an organism during times of stress. temperature regulation in addition to their role in weight control, dynorphins have been found to regulate body temperature. opioid peptides were first investigated in hyperthermia, where it was found that mor agonists stimulate this response when injected into the periaqueductal gray (pag) region of the brain. xin et al. showed that delivery of dynorphin a1-17 (a kor agonist) through microdialysis into the pag region induced hypothermia in rats. the authors found that the severity of hypothermia was proportional to the dose of dynorphin a1-17 administered. hypothermia could be prevented by administering kor antagonist norbni to the rat. xin et al. hypothesized that while mor agonists mediate hyperthermia, kor agonists, such as dynorphin, mediate hypothermia. sharma and alm found that subjecting rats to heat (38˚c) caused dynorphins to be upregulated in the cerebral cortex, hippocampus, cerebellum, and the brain stem. further, authors found that administration of nitric oxide synthase (nos) inhibitors reduced dynorphin a1-17 levels in the brain and attenuated symptoms related to heat stress. sharma and alm concluded that hyperthermia increases dynorphin levels, which may cause damage and promote heat stress reaction. they further hypothesized that nitric oxide was part of this mechanism. ansonoff et al. found that hypothermic effects are mediated through k1 (κ-opioid receptor 1), but not k2. the authors applied a kor agonist to k1 knockout mice, which eliminated hypothermic response. thus, k2 does not appear to have a role in the hypothermic mechanism. clinical significance dynorphin derivatives are generally considered to be of little clinical use because of their very short duration of action.