Intima-media thickness and diameter of carotid and femoral arteries in children, adolescents and adults from the Stanislas cohort: effect of age, sex, anthropometry and blood pressure

OBJECTIVES: To study carotid and femoral intima-media thicknesses and diameters in relation to age, sex, morphologic status and blood pressure. PARTICIPANTS: The subjects were 369 men and women (aged 10-54 years) from the Stanislas cohort, with no known cardiovascular disease. METHODS: Intima-media thicknesses and diameters were measured by B-mode ultrasonography. The effects of sex, age, smoking, anthropometric variables, cholesterol and blood pressure were studied using bivariate and regression analysis. RESULTS: Carotid and femoral intima-media thicknesses were not affected by age nor by sex up to 18 years of age. Thereafter, they increased sharply in men and remained higher than in women. Values were correlated with systolic blood pressure only in men, and with fat-free mass in children and young adults only at the femoral site. Smoking, body mass index and fat mass were associated with intima-media thicknesses only in adults. Carotid diameter was little affected by age during childhood and in adults. Femoral diameter increased up to the age of 18 in both sexes and remained unaffected by age thereafter. This increase was more pronounced in boys, and so values became consistently greater in males aged over 14 years. Carotid diameter was correlated with body mass index or fat mass whereas femoral diameter was correlated with weight or fat-free-mass in children and men. The opposite was observed in women. CONCLUSION: Sex differences occur before adolescence for arterial diameter, but only at an adult age for intima-media thickness. In young subjects, carotid geometry seems to be influenced by blood pressure and excess body weight, while femoral artery geometry seems to be related to blood pressure and body growth.     

Age-associated loss of power and strength in the upper extremities in women and men

Cross-sectional and longitudinal age-associated reductions in power and isometric strength are described for the upper extremities. Over a 25-year period, repeated measures were taken approximately every 2 years from men and women in the Baltimore Longitudinal Study of Aging (BLSA). The longitudinal measures covered an average 9.6 years, range 1-25 years for men and an average 4.6 years, range 1-8 years for women. Strength and power declined beginning by age 40 in both women and men. Thereafter, power declined about 10% more than strength in men, while no significant differences were found in women. Age had a statistically independent influence on strength and power measures after adjusting for gender, height, weight, caloric expenditure, and muscle mass. Twenty-five-year longitudinal analyses in men confirmed the declines observed cross-sectionally, while no changes were observed in women over the 4-5 years of longitudinal data available. Further longitudinal studies are needed to understand the relationships between strength and power losses with age in women. The differences between power and strength changes with age in men argue for the importance of factors other than strength affecting power.     

Mortality from major causes of death and its risk factors in the elderly--26-year follow-up study in Hisayama

The authors studied mortality from major causes of death and risk factors in the elderly in a long-term prospective survey conducted in a Japanese suburban community, Hisayama. In the baseline survey in 1961, we scrutinized 1658 residents of the town aged 40 years or older accounting for 92% of the total population in this age range. Of those, 591 residents (245 men and 346 women) aged 60 years or older, who were free from major cardiovascular disease, were selected for the present study. They were followed-up for 26 years from 1961 to 1987. The average age was 67 years for men and 70 years for women, being significantly higher for women than for men. During the follow-up period, 529 subjects (89.5%) died, and 448 were autopsied (autopsy rate 84.7%). The all-cause mortality (per 1,000 person-years) after adjustment for age was 89.9 for men and 56.7 for women, the former being significantly higher than the latter (p < 0.01). The age-adjusted mortality from cerebrovascular disease was estimated to be 21.4 for men and 9.9 for women, i.e. 8.9 and 8.8 from heart disease, and 19.9 and 10.6 from neoplasm, and 18.1 and 12.2 from-pneumonia, respectively. There was significant sex difference in mortality from cerebrovascular disease, neoplasm and pneumonia (p < 0.01) but not from heart disease (p > 0.1). Multiple Cox's proportional hazards regression analysis showed systolic blood pressure and male sex to be significant risk factors for death by cerebrovascular disease. Systolic blood pressure was also a predictor for death by heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Unco-parahippocampectomy for direct surgical treatment of downward transtentorial herniation

Downward transtentorial herniation is a major cause of death and disability caused by acute supratentorial mass lesions. Thirteen patients, 7 men and 6 women aged from 23 to 75 years old, with progressive transtentorial herniation caused by cerebral contusion with acute subdural haematoma, acute brain swelling after aneurysmal subarachnoid haemorrhage, or massive cerebral infarction were treated by direct surgery using selective removal of the uncus and parahippocampal gyrus (unco-parahippocampectomy). All patients showed progressive deterioration of transtentorial herniation (late third nerve stage or midbrain stage) with unilateral pupillary dilation and absent light reflex. Preoperative Glasgow Coma Scale scores ranged from 4 to 8. Unco-parahippocampectomy was performed via the middle temporal gyrus under the operating microscope. The oculomotor nerve, posterior cerebral artery, and midbrain were directly decompressed. Incision of the arachnoid membrane in the tentorial incisura allowed free communication of the cerebrospinal fluid between the supra- and finfra-cranial fossae to reduce the pressure gradient. Two of the 13 patients died (15%). Two of the 11 survivors (18%) were functionally independent and 1 (9%) required minimal assistance but was independent at home. This series suggests the lifesaving nature of unco-parahippocampectomy in patients with deteriorating clinical condition because of transtentorial herniation.     

Quantitative MR volumetry in Alzheimer's disease. Topographic markers and the effects of sex and education

We determined topographic selectivity and diagnostic utility of brain atrophy in probable Alzheimer's disease (AD) and correlations with demographic factors such as age, sex, and education. Computerized imaging analysis techniques were applied to MR images in 32 patients with probable AD and 20 age- and sex-matched normal control subjects using tissue segmentation and three-dimensional surface rendering to obtain individualized lobar volumes, corrected for head size by a residualization technique. Group differences emerged in gray and white matter compartments particularly in parietal and temporal lobes. Logistic regression demonstrated that larger parietal and temporal ventricular CSF compartments and smaller temporal gray matter predicted AD group membership with an area under the receiver operating characteristic curve of 0.92. On multiple regression analysis using age, sex, education, duration, and severity of cognitive decline to predict regional atrophy in the AD subjects, sex consistently entered the model for the frontal, temporal, and parietal ventricular compartments. In the parietal region, for example, sex accounted for 27% of the variance in the parietal CSF compartment and years of education accounted for an additional 15%, with women showing less ventricular enlargement and individuals with more years of education showing more ventricular enlargement in this region. Topographic selectivity of atrophic changes can be detected using quantitative volumetry and can differentiate AD from normal aging. Differential effects of sex and years of education can also be detected by these methods. Quantification of tissue volumes in vulnerable regions offers the potential for monitoring longitudinal change in response to treatment.     

Sex differences in prefrontal cortical brain activity during fMRI of auditory verbal working memory.

Functional imaging studies of sex effects in working memory (WMEM) are few, despite significant normal sex differences in brain regions implicated in WMEM. This functional MRI (fMRI) study tested for sex effects in an auditory verbal WMEM task in prefrontal, parietal, cingulate, and insula regions. Fourteen healthy, right-handed community subjects were comparable between the sexes, including on WMEM performance. Per statistical parametric mapping, women exhibited greater signal intensity changes in middle, inferior, and orbital prefrontal cortices than men (corrected for multiple comparisons). A test of mixed-sex groups, comparable on performance, showed no significant differences in the hypothesized regions, providing evidence for discriminant validity for significant sex differences. The findings suggest that combining men and women in fMRI studies of cognition may obscure or bias results. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of Ly49A and 5E6(Ly49C) molecules in hybrid resistance mediated by murine natural killer cells against normal T cell blasts

Due to affluence and a sedentary life style a great deal of people in the western countries are affected by coronary heart disease (CHD). The relation between CHD and certain risk factors pertaining to life style is evaluated in this study. A primary purpose is to study certain crucial risk factors for women. The main variables are age, smoking, overweight (measured by BMI), blood pressure and exercise. This prospective study is based on self-reported data from the nation-wide Swedish Level of Living Survey and on data from the national Cause of Death Register. The data were analysed separately by sex using a proportional hazards model. The sample was divided into two strata: those with heart disease and/or diabetes initially, and all the rest. A sample of 2546 men and 2760 women between 45 and 74 years of age was followed from 1980 to the end of 1990. During this period 189 men and 75 women died of coronary heart disease (CHD). It was found that high blood pressure raised the relative risk (RR) of death from CHD by almost 60% in both men and women. Male smokers (> 14 cigarettes a day) had about 60% (significant) and female smokers (> 10 cigarettes a day) 150% (significant) excessive mortality from CHD. Different levels of overweight among women were strongly related to excess mortality from CHD, ranging between 100 and 300%. Among men there was no such relation. Lack of physical activity showed only a weak (non-significant) increased risk of death due to CHD. Diabetes was also found to be an important risk factor for mortality from CHD, especially among women, being seven times as high as among non diabetics. A test of sex differences revealed that there were two significant interactions, namely between sex and overweight, and between sex and age. Background variables in relation to mortality from all cardiovascular diseases (CVD) were also studied. There were of course many similarities between the effects of the background variables in both the disease groups, but there were interesting differences too, e.g. overweight turned out to be a significant risk factor also for men and physical inactivity for women.     

Atrophy of the corpus callosum in Alzheimer's disease versus healthy aging

OBJECTIVE: To investigate the specificity of atrophic changes in the corpus callosum (CC) compared with the cerebellum and pons in patients with Alzheimer Disease (AD), healthy elderly subjects (HE), and a sample of prospectively studied subjects who have developed cognitive decline or "incipient dementia" (ID). DESIGN: Cross-sectional comparison by age using quantitative MRI. SETTING: Ambulatory research unit. PARTICIPANTS: Sixty HE subjects (mean age 78.2 years; range 66-95), 20 ID subjects (mean age 88.1 years; range 78-98) and 39 AD subjects (mean age 72.2 years; range 52-91) were enrolled in longitudinal studies of healthy aging or AD. The population was selected for optimal health; all were examined to exclude medical, neurological and psychiatric illness. MEASUREMENTS: Brain atrophy by quantitative MRI. RESULTS: AD subjects had smaller CC than HE or ID subjects, who did not differ from each other. All three sectors of the CC were smaller in AD than in HE or ID subjects. The cross sectional area of the cerebellum and pons did not differ between groups. HE and ID subjects showed a significant decline in CC size with age. No age-related decline was found for AD subjects. The regional atrophy of the CC in AD subjects was significantly related to cognitive function but not to disease duration. CONCLUSIONS: Atrophy of the CC differentiates HE and ID from AD subjects and tracks the cognitive decline of this disease. In addition, optimally healthy subjects show an age-related decline in callosum size. The atrophy is specific to the CC, a cortical projection system, and does not occur in cerebellum or pons.     

Sonographic measurement of absolute and relative renal length in adults

PURPOSE: The aim of this study was to evaluate sonographically measured absolute and relative lengths of normal kidneys according to subject height, sex, and age. METHODS: Real-time sonography was performed on 202 subjects. Measurements of longitudinal renal diameter represented absolute renal length. Relative renal length was calculated using the kidney length: body height ratio (KBR). RESULTS: Statistical analyses were done on findings in 175 subjects without renal impairment (104 men and 71 women) whose ages ranged from 17 to 85 years (mean +/- SD, 46.3 +/- 17.1). The mean heights of the subjects were 176 +/- 7 cm for men and 167 +/- 6 cm for women. The left kidney was absolutely (mean +/-SD, 112 +/- 9 mm) and relatively (mean KBR +/- SD, 0.655 +/- 0.042) longer than the right kidney (absolute length, 110 +/- 8 mm; KBR, 0.641 +/- 0.038), regardless of sex (p < 0.01). The absolute renal length was significantly greater in men than in women for both kidneys (p < 0.01), but there was no significant difference between KBRs (p > 0.05). Renal length decreased with age, and the rate of decrease seemed to accelerate at 60 years and older. When height and age were included in the multivariate regression analysis, sex was not a significant predictor of kidney length. CONCLUSIONS: Relative renal length better represents kidney size than absolute renal length because it eliminates sex and height differences.     

Validations of time-resolved fluoroimmunoassays for urinary estrone 3-glucuronide and pregnanediol 3-glucuronide

OBJECTIVE: In this study, we determined the effect of age, sex, and body size on left ventricular mass. DESIGN: Two-dimensional-guided M-mode echocardiography was used in an assessment of 111 healthy, normal adults. MATERIAL AND METHODS: Left ventricular mass was calculated with the cube function formula corrected by a regression equation to agree with autopsy estimates of left ventricular mass. Calculated left ventricular mass, indexed by body surface area and by height, was analyzed on the basis of sex and age of the study participants. Age was analyzed as a dichotomous, trichotomous, and continuous variable. The effects of age, sex, and obesity, as well as interactions, were tested within a multiple linear regression model framework. RESULTS: Left ventricular mass, when indexed for either body surface area or height, was greater in men than in women. For women, but not men, we found a small but significant increase in left ventricular mass with advancing age. Body mass index, an indicator of obesity, increased with aging in women but not in men and affected left ventricular mass. No significant changes were noted in left ventricular cavity size with advancing age, and the increase in left ventricular mass in women was due to increased ventricular wall thickness. CONCLUSION: The findings in this study suggest that left ventricular mass, as assessed by two-dimensional-guided M-mode echocardiography, is affected not only by sex and body size but also by age in women. This phenomenon may be related to an increase in body mass index with advancing age in women. In clinical studies that use echocardiographic left ventricular mass to diagnose left ventricular hypertrophy, these observations should be considered.     

Internal jugular to axillary vein bypass for subclavian vein thrombosis in the setting of brachial arteriovenous fistula

Relatively little is known about the epidemiology of carcinoid tumours in contrast to the extensive information available on their biochemical effects and natural history. Accordingly, we have used cancer registrations in England from 1979 to 1987, and in Scotland from 1980 to 1989, to estimate the incidence of carcinoid tumours in Britain. Age-standardised incidence rates for England, based on 3,382 registrations, were 0.71 (0.68-0.75) for men and 0.87 (0.83-0.91) for women, per 100,000 per year. The equivalent rates for Scotland, based on 639 registrations, were 1.17 (0.91-1.44) for men and 1.36 (1.09-1.63) for women. There was a consistent female excess of carcinoid tumours in the reproductive years, which was reversed after the age of 50. The female excess was most striking for gastrointestinal carcinoid tumours in women aged 15-19 years (F:M ratio = 2.14). The sex differences are probably due in part to incidental diagnosis of carcinoid tumours during abdominal procedures, which are more common in women than men at ages 15-49 years. However, there is some evidence to suggest a true sex difference in incidence, particularly the fact that the sex ratio for thoracic tumours varies with age in a similar way to that for gastrointestinal tumours. Hormonal factors may, therefore, be important in the aetiology of carcinoid tumours.     

Fluctuations of sex-related self-attributions as a function of stage of family life cycle.

In a cross-sectional study, sex-related self-attributions of 426 women and 378 men were assessed at 8 stages in the family life cycle. It was hypothesized that sex differences are not fixed in adulthood but fluctuate according to the demand characteristics of various life situations. Factor analysis of the Bem Sex-Role Inventory yielded 9 factors, providing a more precise evaluation of how desirable and undesirable aspects of instrumentality and expressivity vary throughout adulthood. The majority of effects were related to stage of family life and not age. On 1-way ANOVA, compassion and tenderness showed stage-of-life effects for both sexes, but autonomy and leadership showed effects only for men. Cross-sex-typed attributes were prominent during grandparenthood, with a rise in expressiveness for men and a rise in autonomy for women. Men were more autonomous and less acquiescent than women during expectancy and young parenthood but not at other stages. Women showed more tenderness than men at all stages except among the married-childless and grandparents. There were few sex differences across the different states of life in nonassertiveness and social inhibitions. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of sex and lesion locus on measures of intelligence.

Previous reports of the cognitive effects of lateralized brain damage in men and women have been conflicting, some suggesting significant differences in the pattern of intellectual deficits and others failing to do so. This article reports Wechsler Adult Intelligence Scale (WAIS) IQ data from 64 patients with cortical neoplasms confined to one of four brain quadrants. Analyses indicated a significant main effect for lesion laterality for verbal IQ scores (but not for performance IQ scores) as well as for verbal IQ–performance IQ difference scores. There were no significant main effects for sex or lesion site (in the anterior–posterior dimension) and no significant interactions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of estrogen replacement therapy on PET cerebral blood flow and neuropsychological performance

Reports that estrogen may protect against age-associated memory decline and Alzheimer's Disease have kindled interest in the effects of estrogen replacement therapy (ERT) on cognition and brain function. As part of a 9-year study in the Baltimore Longitudinal Study of Aging, we are performing annual magnetic resonance imaging, positron emission tomography (PET), and neuropsychological assessments to examine brain structure and function in individuals aged 55 and older. PET measurements of regional cerebral blood flow (rCBF) are obtained under 3 conditions: rest and verbal and figural delayed recognition memory tasks. Fifteen women receiving ERT (with or without the addition of progesterone) were compared with a matched sample of 17 untreated women. There were no significant differences between groups in regional brain volumes or ventricular size. However, ERT users and nonusers showed significant differences in PET-rCBF relative activation patterns during the memory tasks. During verbal memory processing, there were significant interactions in rCBF activations for the right parahippocampal gyrus, right precuneus, right frontal regions, and left hypothalamus. During figural memory processing, significant interactions were observed for right parahippocampal and inferior parietal regions and for left visual association and anterior thalamic regions. ERT users also showed better performance on neuropsychological tests of figural and verbal memory and on some aspects of the PET activation tests, although the two groups did not differ in education, overall verbal ability, or performance on other neuropsychological tests. These findings confirm our previous observation of the beneficial effects of ERT on figural memory. Moreover, differences in rCBF activation patterns between ERT users and nonusers suggest an area for future research to examine mechanisms through which ERT may influence memory and other cognitive abilities.     

Euthanasia and doctor-assisted suicide: responses by oncologists and non-oncologists

Plasmatic arterial necrosis and microaneurysm of small arteries are preceded by smooth muscle cell loss and the rupture of these arterial lesions is a direct cause of hypertensive intracerebral hemorrhage. The hypertensive brainstem hemorrhage occur exclusively in the pons. To elucidate whether there are differences of underlying arterial lesions between each part of the brainstem or not, small arteries in normal 34 autopsied brainstems were investigated histologically and morphometrically. Histological study revealed the predilection of the occurrence of plasmatic arterial necrosis, microaneurysms and fibronodular arterial lesions in the hypertensive pons. These lesions occurred predominantly in the small arteries 100-300 microns in diameter in the basal part of hypertensive pons, and were rare in the other parts of hypertensive brainstems and in normotensive brainstems. A negative correlation between the ratio of number of smooth muscle cell nuclei to the area of tunica media and age was demonstrated morphometrically. The ratio in the hypertensive group was significantly lower than that of the normotensive group. In addition the mean ratio in the pons was significantly lower than that in the midbrain and the medulla oblongata in the hypertensive group. These results are consistent with the fact that the hypertensive brainstem hemorrhage predominantly occur in the pons and primary bleedings in the other parts of the brainstem are rare.     

The spontaneous aortocaval fistula: a complication of the abdominal aortic aneurysm. Case report and review of the literature

AIMS: (i) to compare Helicobacter pylori serology in two 70-year-old cohorts in Gothenburg, Sweden, born 21 years apart, (ii) to study H. pylori serology in a 70-year-old cohort over 20 years. POPULATION AND METHOD: H. pylori serology at the age of 70 was investigated in 98 men and 132 women born in 1901/02 and in 77 men and 113 women born in 1922. In 21 men and 40 women Helicobacter serology was monitored longitudinally with examinations at 70, 81, and 90 years of age. The analyses were performed on frozen samples by use of an in-house enzyme immunoassay with a sensitivity of 0.99, specificity of 1.00 and positive and negative predictive values of 0.96 and 1.00, respectively. Absorbance values <0.500 were interpreted as negative; values of > or = 0.700 were interpreted as positive, and values in between as inconclusive. RESULTS: The 70-year-old cohort, born in 1922, showed a significantly lower proportion of subjects with positive H. pylori serology in both men (57.1% vs 80.6%) and women (48.7% vs 75.8%) compared with 70-year-olds born in 1901/02. There were no significant sex differences in either cohort. No longitudinal increase or decrease could be demonstrated in those who were examined at 70, 81 and 90 years of age. CONCLUSIONS: The difference in H. pylori prevalence between the two cohorts may reflect a rapid change in socio-economic conditions in Sweden during this 20-year period.     

Body size and physique among Canadians of First Nation and European ancestry

The purpose of this study was to compare body size and physique among Canadians of Aboriginal (First Nation [FN]) and European ancestry (EA) from the northern Ontario communities of Temagami and Bear Island. The sample consisted of 130 FN and 494 EA participants including adults (20-75 years: 214 men, 234 women) and youth (5-19 years: 97 boys, 79 girls). Indicators of body size and physique included stature, the sitting height-to-stature ratio (SSR), body mass, BMI, estimated upper-arm muscle area, biacromial, bicristal, biepicondylar, and bicondylar breadths, and the Heath-Carter anthropometric somatotype (endomorphy, mesomorphy, and ectomorphy). There were few differences in body size between FN and EA, with the exception of adult females. Adult FN females were significantly heavier and had greater bone breadths than EA women (P < 0.001). On the other hand, somatotype differed significantly between EA and FN by age and sex, except for 5-19-year-old females. Among boys and men, FN had greater endomorphy (P < 0.03), whereas FN men also had lower ectomorphy (P < 0.01). Among women, FN were significantly more endomorphic and mesomorphic and less ectomorphic (P < 0.001). Although results for 5-19-year-old females were not significant, they were in the same direction as the other groups (greater endomorphy). Forward stepwise discriminant function analyses indicated that endomorphy was the most important discriminator between FN and EA by age and sex.     

Effects of hospital closure on mortality rates of the over-65 long-stay psychiatric population

We describe a girl with a brain-stem tumour and symptoms very similar to those of Rett syndrome (RS). Her early history was uneventful and development was normal (except for hypotonia). At the age of 6 months her development slowed. Subsequently, deterioration occurred and the features characteristic of RS were seen: loss of purposeful hand use, stereotypic hand movements, impaired social contact, decelerated head growth, and ataxia. Cerebral CT at the age of 3 years and 4 months revealed a tumour in the region of the pons and hydrocephalus. We suggest that a pons/midbrain tumour appearing at an early age may affect the developing CNS and cause symptoms similar to those of RS. A possible causal connection between midbrain pathology and RS is supported by this case.     

Sex differences in brain regions activated by grammatical and reading tasks

Do the brains of men and women show similar patterns of functional organization for language, or are men more strongly lateralized? We used PET to measure cerebral blood flow (CBF) as men and women read real and nonce verbs, and produced past tense forms. While the overall patterns of reaction time, error, and brain activation were similar, there were also significant sex-related differences in CBF patterns. During the past tense generation tasks, men showed left-lateralized activation while women recruited bilateral perisylvian cortex, confirming differences in functional laterality. During all tasks, women showed higher activation in occipital and/or cerebellar regions, suggesting differences in basic reading strategies. We conclude that sex differences in functional cortical organization exist in the absence of significant behavioral differences.     

Naloxone-precipitated changes in biogenic amines and their metabolites in various brain regions of butorphanol-dependent rats

Influence of a naloxone (an opioid receptor antagonist) challenge (5 mg/kg, IP) on levels of biogenic amines and their metabolites in various brain regions of rats infused continuously with butorphanol (a mu/delta/kappa mixed opioid receptor agonist; 26 nmol/microliter/h) or morphine (a mu-opioid receptor agonist; 26 nmol/microliter/h) was investigated using high-performance liquid chromatography with electrochemical detection (HPLC-ED). Naloxone precipitated a withdrawal syndrome and decreased the levels of: dopamine (DA) in the cortex and striatum, 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum, homovanilic acid (HVA) in the striatum, limbic, midbrain, and pons/medulla regions in butorphanol-dependent rats. However, the levels of norepinephrine (NE), serotonin (5-hydroxytryptamine; 5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in the regions studied were not affected by naloxone-precipitated withdrawal. In addition, naloxone increased the HVA/DA ratio in the cortex, while this ratio was reduced in the limbic, midbrain, and pons/medulla. The reduction of 5-HIAA/5-HT ratio was also detected in the limbic area. In the animals rendered dependent on morphine, the results obtained were similar to those of butorphanol-dependent rats except for changes of 5-HIAA levels in some brain regions. These results suggest that an alteration of dopaminergic neuron activity following a reduction of DA and its metabolites in specific brain regions (e.g., striatum, limbic, midbrain, and pons/medulla) play an important role in the expression of the opioid withdrawal syndrome.