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Introduction: Cardiovascular disease (CVD) is one of the global leading causes of morbidity and mortality in chronic kidney disease (CKD) patients. Vascular calcification (VC) is a major cause of CVD in this population and is the consequence of complex interactions between inhibitor and promoter factors leading to pathological deposition of calcium and phosphate in soft tissues. Different pathological landscapes are associated with the development of VC, such as endothelial dysfunction, oxidative stress, chronic inflammation, loss of mineralization inhibitors, release of calcifying extracellular vesicles (cEVs) and circulating calcifying cells., Areas Covered: In this review, we examined the literature and summarized the pathophysiology, biomarkers and focused on the treatments of VC., Expert Opinion: Even though there is no consensus regarding specific treatment options, we provide the currently available treatment strategies that focus on phosphate balance, correction of vitamin D and vitamin K deficiencies, avoidance of both extremes of bone turnover, normalizing calcium levels and reduction of inflammatory response and the potential and promising therapeutic approaches liketargeting cellular mechanisms of calcification (e.g. SNF472, TNAP inhibitors).Creating novel scores to detect in advance VC and implementing targeted therapies is crucial to treat them and improve the future management of these patients.

Urban seismic networks are considered very useful tools for the management of seismic emergencies. In this work, a study of the first urban seismic network in central Italy is presented. The urban seismic network, built using MEMS sensors, was implemented in the urban district of Camerino, one of the cities in central Italy with the greatest seismic vulnerability. The technological choices adopted in developing this system as well as the implemented algorithms are shown in the context of their application to the first seismic event recorded by this innovative monitoring infrastructure. This monitoring network is innovative because it implements a distributed computing and statistical earthquake detection algorithm. As such, it is not based on the traces received by the stations from the central server; rather, each station carries out the necessary checks on the signal in real time, sending brief reports to the server in case of anomalies. This approach attempts to shorten the time between event detection and alert, effectively removing the dead times in the systems currently used in the Italian national network. The only limit for an instant alarm is the latency in the tcp/ip packages used to send the short reports to the server. The presented work shows the infrastructure created; however, there is not enough data to draw conclusions on this new early warning approach in the field, as it is currently in the data collection phase.

Objectives: Rehospitalizations for elderly patients are an increasing health care burden. Nonetheless, we have limited information on unplanned rehospitalizations and the related risk factors in elderly patients admitted to in-hospital rehabilitation facilities after an acute hospitalization., Setting: In-hospital rehabilitation and aged care unit., Design: Retrospective cohort study., Participants: Elderly patients 65 years or older admitted to an in-hospital rehabilitation hospital after an acute hospitalization between January 2004 and June 2011., Measurements: The rate of 30-day unplanned rehospitalization to hospitals was recorded. Risk factors for unplanned rehospitalization were evaluated at rehabilitation admission: age, comorbidity, serum albumin, number of drugs, decline in functional status, delirium, Mini Mental State Examination score, and length of stay in the acute hospital. A multivariable Cox proportional regression model was used to identify the effect of these risk factors for time to event within the 30-day follow-up., Results: Among 2735 patients, with a median age of 80 years (interquartile range 74-85), 98 (4%) were rehospitalized within 30 days. Independent predictors of 30-day unplanned rehospitalization were the use of 7 or more drugs (hazard ratio [HR], 3.94; 95% confidence interval, 1.62-9.54; P = .002) and a significant decline in functional status (56 points or more at the Barthel Index) compared with the month before hospital admission (HR 2.67, 95% CI: 1.35-5.27; P = .005). Additionally, a length of stay in the acute hospital of 13 days or more carried a twofold higher risk of rehospitalization (HR 2.67, 95% CI: 1.39-5.10); P = .003)., Conclusions: The rate of unplanned rehospitalization was low in this study. Polypharmacy, a significant worsening of functional status compared with the month before acute hospital admission, and hospital length of stay are important risk factors., (Copyright © 2013 American Medical Directors Association, Inc. All rights reserved.)

Background: Although delirium is known as a mental disorder, recent evidence suggests that it is associated with short- and long-term impairment of functional status., Objective: To evaluate whether a pattern of fluctuations in motor performance are a diagnostic sign of delirium., Design: Case-controlled study with prospective evaluations of 4 groups of patients., Setting: Department of Rehabilitation and Aged Care., Methods: Fifteen patients with incident delirium alone (Del group) and 15 patients with incident delirium superimposed on dementia (DSD group) were compared with 15 patients with neither delirium nor dementia (No Del-No Dem group) and 15 patients with dementia but no delirium (Dem group), respectively. Eligibility criteria were age 65 years or older, ability on admission to maintain sitting position for at least 10 minutes, and absence of visual/hearing impairment or delirium on admission. All patients underwent a multidimensional assessment on admission and serial evaluations of motor performance using Trunk Control Test (TCT) and Tinetti scale. These assessments were fixed at 5 different times, coincident with admission (T(0)), predelirium (T(1)), onset of delirium (T(2)), resolution of delirium (T(3)), and discharge (T(4))., Results: Patients in the Dem, DSD, and Del groups were significantly more impaired at T(0) in cognitive and functional status and motor performance compared with No Del-No Dem patients. At T(1) all groups improved, although in different ways. At T(2) only in the Del and DSD groups, but not in the others, there was a pattern of decline in TCT and Tinetti scores (P < .0005 at t test for pair comparison for both tests) and a specular pattern of improvement at T(3) (P < .0005 at t test for pair comparison for both tests). Patients in the Del and DSD groups had the poorest attentive and executive performances at T(2), which significantly improved at T(3). In No Del-No Dem and Dem groups, attentive and executive functions did not change from T(2) to T(3.), Conclusion: Patients with delirium exhibit a pattern of fluctuating motor performance that is chronologically related with the onset and the end of delirium, ie, they decline when delirium develops and improve when delirium ends. This pattern seems to be typical of delirium, as it is appreciable in subjects with dementia developing delirium but not in patients with dementia alone. A fluctuation of motor performance should be considered a diagnostic sign of delirium., (Copyright © 2011 American Medical Directors Association. Published by Elsevier Inc. All rights reserved.)

Objectives: To assess the impact of clinical instability (CI) and delirium on admission to a rehabilitation unit on clinical and functional outcomes (death, transfer to acute care, poor functional recovery) at discharge, in a population of elderly patients., Design: Observational study., Setting: Rehabilitation and Aged Care Unit (RACU)., Participants: Participants were 583 consecutively and firstly admitted elderly patients., Measurements: On admission, all patients underwent a comprehensive geriatric assessment including sociodemographics, cognitive and depressive symptoms, nutritional status, physical health, and functional status. CI was recorded for all patients on admission, assessing 5 vital signs (temperature, heart rate, systolic blood pressure, respiratory rate, and oxygen saturation). Delirium was assessed daily with the Confusion Assessment Method., Results: Patients were on average old (mean age: 77.8 +/- 9.8), predominantly female (68.6%), with mild cognitive deterioration (MMSE: 22.1 +/- 6.3) and depressive symptoms (GDS: 5.9 +/- 3.5). They had moderate comorbidity (means CIRS: 3.1 +/- 1.9), and functional impairment both before (Barthel Index pre-admission: 84.5 +/- 19.2; IADL: 3.3 +/- 3.0) and on admission (Barthel Index: 55.8 +/- 27.5). On admission, 136 (23.3%) patients were classified as clinically unstable: 76 (13%) had either CI or delirium, and 60 (10.3%) had CI associated to delirium. At discharge, 26 patients were transferred to acute care hospitals, and 14 died. Transfer to acute care occurred in more than 10% of patients with almost one altered condition (CI or delirium), and in one fifth of patients with the association of CI and delirium. In-RACU death was observed only in this latter group. Functional recovery at discharge was significantly higher in stable patients than in patients with CI and/or delirium., Conclusions: CI and delirium are useful prognostic markers of adverse clinical and functional outcomes in a population of elderly subjects admitted to a rehabilitative unit., (2010 American Medical Directors Association. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Benign paroxysmal positional vertigo (BPPV) of lateral semicircular canal (LSC) is one of the rarer forms of BPPV as compared to posterior semicircular canal BPPV. Various particle repositioning manoeuvres have been described in the literature as a mode of treating this condition., Purpose: Evaluation and discussion of the procedure of the Gufoni's manoeuvre and its advantages in the treatment of BPPV of LSC., Material and Methods: Prospective study of 58 patients affected by LSC BPPV who were office-treated with Gufoni's manoeuvre., Results: Seventy-nine percent of the patients so treated had complete resolution of symptoms, and 6.9% did not show any improvement in their symptoms. The remaining 13.8% had a conversion into posterior semicircular canal BPPV during treatment and were successfully treated with Epley's or Semont's manoeuvre., Conclusions: Gufoni's manoeuvre is effective in treating patients suffering from BPPV of LSC; it is simple to perform; there are not many movements to execute, it needs low time of positioning, and positions are comfortable to the patient.

The formation of amyloid-containing senile plaques and tau-rich neurofibrillary tangles are central events in Alzheimer disease (AD) pathogenesis. Significantly, ABalphaC, a major protein phosphatase 2A (PP2A) holoenzyme, specifically binds to and dephosphorylates tau. Deregulation of PP2A results in tau hyperphosphorylation in vivo. Here, we compared the expression levels and distribution of PP2A subunits in various brain regions from autopsy cases of AD and aged controls with or without histological evidence of age-related neurofibrillary degeneration. Immunoblotting analyses revealed that there was a significant reduction in the total amounts of ABalphaC in AD frontal and temporal cortices that matched the decrease in PP2A activity measured in the same brain homogenates. Immunohistochemical studies showed that neuronal ABalphaC expression levels were significantly and selectively decreased in AD-affected regions and in tangle-bearing neurons, but not in AD cerebellum and in non-AD dementias. Reduced neuronal ABalphaC immunoreactivity closely correlated with tangle load, but not plaque burden, suggesting that ABalphaC dysfunction contributes to AD tau pathology. Glial cells within senile plaques were also positive for ABalphaC. Increased glial PP2A immunoreactivity was observed in both AD and non-AD cases and may play a role in the brain's response to general inflammatory processes and amyloidogenesis.

The adenosine agonist cyclohexaladenosine injected into the medial pontine reticular formation of the rat induces a long-lasting increase in rapid eye movement sleep. To investigate the adenosine receptor-subtype(s) mediating this effect, the dose-response relationships for increasing rapid eye movement sleep by two highly selective adenosine receptor agonists were compared. Rats were surgically prepared for chronic sleep recording and bilateral guide cannulae were aimed at medial sites in the caudal, oral pontine reticular formation. Injections were made unilaterally in 60 nl volumes within 1 h after lights-on. The adenosine agonists used were A1-selective cyclohexaladenosine (10(-6)-10(-4) M) and A2a-selective CGS 21680 (10(-7)-10(-3) M). Each animal also received a series of three, paired-consecutive injections of the muscarinic receptor antagonist atropine (4x10(-3) M) followed by the lowest effective dose of each agonist or saline as control. The A2a receptor agonist, CGS 21680, was one order of magnitude more potent than the A1 receptor agonist, cyclohexaladenosine, in inducing rapid eye movement sleep increases. Preinjection of atropine at a dose that did not itself affect rapid eye movement sleep resulted in antagonism of CGS 21680, but not cyclohexaladenosine-induced rapid eye movement sleep. The differential sensitivity of these ligands to antagonism by atropine supports the conclusion that both A1 and A2a adenosine receptor subtypes in the reticular formation subserve agonist-induced rapid eye movement sleep and that they do so by independent mechanisms. The A2a mechanism requires the cholinergic system and may act through the increased release of acetylcholine. The A1 mechanism operates at a different locus possibly through an inhibition of GABA neurotransmission.

The use of Alendronate for the treatment of senile diabetes with osteopenia or osteoporosis is a common practice today, although the reasons for the success of this treatment are not completely understood. We investigated 40 elderly female patients, over 70 years of age, divided in two Groups (A and B) 20 cases of each, with insulin-dependent senile diabetes and fair metabolic balance, with an average disease duration of 30 +/- 4 years. They all had osteoporosis shown by the mean T-score of bone mineral densitometry. The Groups were treated as follows, Group A with 10 mg/day of Alendronate per os, with morning fasting plus a supplementation of calcium and vitamin D3, while the Group B received only calcium and vitamin D3 per os. Bone mineral density (BMD) expressed in mg/cm2, and in terms of T-score and Z-score at the spine (L1-L4) was monitored over time after 12 and 24 months, using dexa technique with a Lunar DPX densitometer. Moreover, the variation of daily consumption of insulin (DCI) of all the study population was calculated 12 and 24 months after the start of treatments. The data of Group A showed an improvement of osteoporosis, as evidenced by the increase of BMD at both times of measurement, accompanied by a significant reduction in the DCI (-21.6% by the 12th month, and -36.2% by the end of the observation period). In the Group B only small, statistically insignificant changes were observed in both the BMD and DCI. The most plausible explanation of reduction of DCI in Group A seems to be that Alendronate has improved the clinical symptoms of osteoporosis (pain, rigidity, and reduction of movements) through its action on the bone mass recovery and slowing down the bone turnover and under these conditions the diabetic patients improved their own physical performance. The better and more extensive movements certainly produced a reduction in the DCI, since a correct and adequate physical activity does contribute to an improved glucose metabolism.

Obesity has gained a great importance during the last decades, and this fact stimulated numerous studies regarding the genetic causes of this disease. A recently discovered new molecule, called leptin, raised a wide interest. It is a product of the adipocytes, it exerts inhibitory effects on the center of appetite and increases the energy expenditure of the organism. The present study evaluated blood leptin levels in 57 elderly subjects and searched for eventual correlations between this parameter and the age, the body mass index (BMI), the fat body mass (fat%), the waist (W) and hip (H) circumference, as well as the ratio (R) of these latter two values (WHR). Blood leptin levels do not correlate with age, body height and the WHR, but display significant positive correlations with the body weight, the BMI, the fat%, the W, H and WHR. A deeper knowledge on leptin and the correlations of this hormone with other body parameters might be helpful in a better understanding of several pathogenetic mechanisms related to aging and involved in a deterioration of the quality of life in elderly, like multiple atherosclerotic and metabolic diseases (diabetes, dyslipidemias).

This study was aimed at evaluating the correlation between bone mineral density (BMD) and the psychophysical health status in an elderly study population (62 subjects, mean age 84+/-5 years, 21 males and 41 females), institutionalized (Group A) in various structures of Pozzallo, a marine locality of the Ragusa Province in Sicily. BMD was measured by using ultrasonography of the calcanear area (T-score, Z-score, stiffness). The alterations of the cognitive and affective spheres as well as the levels of autonomy and autosufficiency were estimated by means of psychometric scales like mini-mental state examination (MMSE), geriatric depression scale (GDS), activities of daily living (ADL) and instrumental activities of daily living (IADL). Other biological, social and health-related factors, such as age, sex, body weight and height, nutritional and drug-taking habits, physical activity and previous pathologies, were also considered. These variables were compared to those obtained in a similar, but non-institutionalized controls (Group B) of 63 subjects (mean age 85+/-2 years, 27 males and 36 females), being similar in number and age distribution, frequenting the Geriatric Day Center of the same locality. Statistical analysis revealed significant differences between Groups A and B: the BMD was considerably lower, but also the cognitive and affective performances were strongly reduced in Group A. These findings can be attributed to decreased psychosensorial stimuli and lost interest of the patients in Group A, resulting in a lower physical activity, accompanying the depressive state, and may represent the first signs of a decreased intellectual performance, which can later be transformed into dementia. The functional abilities and the levels of autonomy are also reduced, risking the loss of autosufficiency. Also, the drug usage was different in Group A: more sedative-hypnotics and anticoagulants were consumed. As regards the polymorbidities, arterial hypertension and consequent chronic renal failure, hepatopathies and thyreopathies were most frequent, these latter two being more frequent in the Group A.

Twenty patients affected by fever of unknown origin (FUO), due to a likely infection of the muscular or skeletal tissues, were studied by a Total Body scan with a monoclonal antibody fragment (Leukoscan) labelled with Tc-99m. The diagnostic procedure helped reach a final diagnosis in 8 out of the 20 patients because it identified the focus of the infection of the muscles or bones in joint proximity. Our data show that Leukoscan deserves to become a first line diagnostic procedure in the diagnostic algorithm for the evaluation of patients with FUO.

Dehydroepiandrosterone (DHEA) is a precursor of sex hormones in mammals. Dietary DHEA serves to prevent or inhibit various diseases and also lengthens life spans of animals. Moreover, dietary DHEA inhibits food intake in certain strains of mice. We administered DHEA (0.45% w/w of food) to C57BL/6 (B6) and (B6 x DBA/2)F1 (BDF1) mice for 5 weeks. Food intake was inhibited in both strains of mice during the first week. Thereafter, B6, but not BDF1, mice consumed less food. Because hypothalamic serotonin and/or dopamine regulate appetite, satiety and other behaviors, the hypothesis tested was that hypothalamic concentration of serotonin, dopamine and/or their metabolites are affected differentially in B6 and BDF1 mice fed DHEA. In another study, mice were fed the AIN-76A diet with or without DHEA for 1 and 7 days or were pair-fed to DHEA-fed mice for 7 days. On Day 1 of DHEA feeding (acute effects) hypothalamic levels of serotonin, dopamine, and metabolites were unchanged in B6 mice, but levels of dopamine were increased and levels of dopamine metabolites were decreased in BDF1 mice. On Day 7 of DHEA feeding, levels of serotonin were increased in BDF1 but not B6 mice. On Day 7 of pair-feeding there were decreased levels of hypothalamic dopamine metabolites in BDF1 but not B6 mice. Paraventricular nuclei of BDF1 mice had decreased levels of serotonin but not of dopamine in all groups. Serum levels of DHEA and its metabolite, 5-androstene-3beta,17beta-diol, correlated significantly only with serotonin concentrations in BDF1 mice. The salient findings of these experiments are that DHEA inhibits food intake to a greater extent in B6 than in BDF1 mice. However, alterations of hypothalamic neurotransmitters were greater in BDF1 than in B6 mice. Because BDF1 and B6 mice share B6 genes, relevant gene(s) derived from DBA/2 mice might mediate the different responses detected.

The authors report a case of hypogonadotropic and hypothyrotropic partial hypopituitarism, being treated for over sixteen years with a substitution therapy consisting of estroprogestogenal hormones and L-thyroxine, presenting severe secondary osteoporosis, detected by densitometric examination (DEXA) of the medial and ultradistal sites of the non dominant radius. The patient was treated with alendronate (10 mg/die) for two years, in addition to the estroprogestogen therapy, resulting in a significant recovery of bone mass, equal to 16% compared to initial values, reaching near normal bone density values. On analysing the mechanisms of action of the bisphosphonates, the estrogens and the L-thyroxines, the authors suggest a synergic mechanism between the estrogen and the alendronate, which act on the bone turn-over at different times. Also, the alendronate would seem to antagonise the osteopenia of L-thyroxine, though this mechanism is still unknown.

Among the age-related pathophysiological alterations of the brain, the anomalies of the white matter are becoming of increasing interest at both pathological and clinical levels. Wherever specific pathologies of the white matter can be excluded, the still encountered anomalies are generally defined as leukoaraiosis (from the Greek words white and rarefaction), in order to indicate certain ill-defined, slurred subcortical areas which may be single, multiple, or confluent, representing transparent white matter regions, most probably of ischemic origin. The causes, risk factors and clinical significance of leukoaraiosis have remained so far unknown. At clinical level, it is believed to be connected with cognitive and affective disorders. This study intended to collect evidence of the presence and to estimate the extent of eventual cognitive and affective disorders in a sample of elderly patients displaying cerebral lesions like simple or associated leukoaraiosis, as well as other stabilized focal, single or multiple ischemic lesions, cerebral atrophy, lacunar state and vascular cerebropathies without leukoaraiosis. So far no significant correlations have been encountered between the neurodiagnostic and psychometric findings.

These studies were conducted on 38 female patients treated with alendronate (10 mg/day, per os) for 3 years, because of osteoporosis. Of these patients, 29 were in the menopausal age longer than 10 years, and the remaining nine patients were in menopausa shorter than 10 years. Urine sample were taken at the start of the treatment and every 6 months afterward for 3 years, and crosslinked N-telopeptides of type I collagen (NTx) have been measured in them by means of an ELISA technique. Bone mineral density (BMD) has been recorded at the ultradistal (UDBMD) and mediodistal (MDBMD) region of radius of the non-dominant side. Body mass index (BMI) of the subjects has also been determined each time. The baseline values of NTx varied very much, scattered in a range of 11-215 nanomoles bone collagen equivalent/millimoles creatinine (nM BCE/mM Cr), in average 59+/-46; those of UDBMD and MDBMD amounted to 258+/-63 and 587+/-112 mg/cm(2), respectively. NTx, the BMD values and the menopausal age does not correlate with cach other. Both BMD values increased almost linearly in the total study pool during the 3-years-long treatment, being 3.0-9.2 and 0.8-2.5% higher in terms of UDBMD and MDBMD, respectively. Urine NTx concentrations decreased during the same time 30-35%. It is concluded that monitoring of urine NTx levels may be very useful during antiosteoporotic treatments, because a reduction of NTx is an indicator of the slowing down of bone turnover and the bone losses, as was observed during the alendronate therapy.

The purpose of this study was to assess the prevalence of cognitive and affective disorders in a group of elderly people suffering from chronic renal failure (CRF) and undergoing outpatient hemodialysis. Psychogeriatric assessment was performed on 39 individuals over 65 years of age suffering from CRF, and on a control group composed of 35 healthy elderly individuals. Assessment was made through Mini Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Activity Daily Living (ADL) and Instrumental Activity Daily Living (IADL) shortly before hemodialysis. A number of blood parameters were determined for both groups to evaluate the state of metabolic compensation. The elderly people undergoing hemodialysis did not seem to present a greater decline in cognitive capacity than their healthy peers, even if this is closely related to the level of anemia present in hemodialysis patients. On the other hand, affective disorders were widely observed, although in mild form, and seem to depend on factors other than age. There is certainly a reactive element deriving from the hemodialysis condition itself and the problems related to it, whereas an organic element linked to CRF cannot be excluded, and which seems to be related to anemia. Finally, the level of independence does not seem to be compromised in hemodialysis patients.

Numerous studies have suggested a marked correlation between thyroid functionality indices and lipid metabolism. In this trial we assessed the functional parameters of 165 individuals over 70, 87 women and 78 men, correlating the serum values of T3, T4, FT4, TSH with cholesterol, triglycerides, HDL, Apo-A and Apo-B levels. The correlation was performed over the whole population studied and subsequently, after dividing the population by sex and age (3 age groups: A, 70-75; B, 76-80; C, over 80) in the individual groups. In the population as a whole, we have observed a statistically significant correlation between T4/cholesterol (P=0.0001); T3/cholesterol (P=0.06); T4/triglycerides (P=0.0001); T3/triglycerides (P=0.09); T4/HDL (P=0.0001); T4/Apo-A (P= 0.02); T3/Apo-A (P=0.008); T4/Apo-B (P=0.0001). Analysis by gender shows a statistically significance between the female and male sexes in the correlation between T3/cholesterol (P=0.001); T3/triglycerides (P=0.06); T4/cholesterol (P=0.0001) and T4/triglycerides (P=0.0001). When the data were analyzed by age, in Group A (75-80) there was no statistically significant correlation, whereas in Group B (76-80) there has been an increase in significance in the correlation between T3/cholesterol (P=0.006); T3/triglycerides (P=0.001); T3/Hdl (P=0.08); T3/Apo-A (P=0.0001); T3/Apo-B (P=0.08); T4/cholesterol (P=0.00001) and ); T4/Apo-A (P=0.0001). On the other hand in the Group C age group (over 80) this significance is considerably lower. Maybe this decrease of correlations should be attributed to a global savings of the older organisms, or to a process of natural selection.

We have previously shown that during the post-natal critical period of development of the cat visual system, 1 week of instrumental rapid eye movement (REM) sleep deprivation (IRSD) during 2 weeks of monocular deprivation (MD) results in significant amplification of the effects of solely the 2-week MD on cell-size in the binocular segment of the lateral geniculate nucleus (LGN) [36,40]. In this study, we examined whether elimination of ponto-geniculo-occipital (PGO)-wave phasic activity in the LGN during REM sleep (REMS), rather than suppression of all REMS state-related activity, would similarly yield enhanced plasticity effects on cell-size in LGN. PGO-activity was eliminated in LGN by bilateral pontomesencephalic lesions [8,32]. This method of removing phasic activation at the level of the LGN preserved sleep and wake proportions as well as the tonic activities (low voltage, fast frequency ECoG and low amplitude EMG) that characterize REM sleep. The lesions were performed in kittens on post-natal day 42, at the end of the first week of the 2-week period of MD, the same age when IRSD was started in the earlier study. LGN interlaminar cell-size disparity increased in the PGO-wave-suppressed animals as it had in behaviorally REM sleep-deprived animals. Smaller A1/A-interlaminar ratios reflect the increased disparity effect in both the REM sleep- and PGO-suppressed groups compared to animals subjected to MD-alone. With IRSD, the effect was achieved because the occluded eye-related, LGN A1-lamina cells tended to be smaller relative to their size after MD-alone, whereas after PGO-suppressing lesions, the A1-lamina cells retained their size and the non-occluded eye-related, A-lamina cells tended to be larger than after MD-alone. Despite this difference, for which several possible explanations are offered, these A1/A-interlaminar ratio data indicate that in conjunction either with suppression of the whole of the REMS state or selective removal of REM sleep phasic activity at the LGN, altered visual input evokes more LGN cell plasticity during the developmental period than it would otherwise. These data further support involvement of the REM sleep state in reducing susceptibility to plasticity changes and undesirable variability in the course of normative CNS growth and maturation., (Copyright 1999 Elsevier Science B.V.)

The authors evaluated the efficacy of an electronic treatment for pain, using an ion flow generator, BE-101 model by Bio-Ejt, on 19 patients suffering from acute pain of an arthrorheumatic nature. Each patient was treated for two weeks every other day (6 sittings), each sitting lasting 20 minutes at an intensity of about 30 microAmper for both transducers. The results demonstrated that this technique is very effective in curing the pain.

Study Objectives: In this study, we test the hypothesis that when REM-state activation (which impinges upon all lateral geniculate nucleus laminae irrespective of stimulating eye) is deprived, the monocular segment (MS) that is cut off from visual input and also deprived of REM-state activation will exhibit smaller cells, owing to the loss of extrinsic as well as intrinsic activation., Design: We carried out a study comparing soma sizes in the MSs of kittens subjected to monocular deprivation (MD) + REM deprivation (RD) to two age-matched nonRD groups, MD ONLYs and MD MOMS (MD kittens living in their home cages)., Measurements and Results: Perikaryal outlines of 100 cells in each of the bilateral MSs were measured. As predicted, mean cell size in the MS connected to the patched eye of MD + RD kittens, but in neither of the control groups, was significantly smaller than in the MS afferented by the nonpatched eye. One-way ANOVAs comparing MS cell-size means from the same sides across groups were also significant, but the two MSs showed different results on post hoc tests. The ordering of MS cell-size means correlated significantly with a measure that aggregates the sources of activation reaching a particular MS and their durations., Conclusions: These results reveal that removal of REM-state activation during CNS development amplifies the plasticity processes generated when normal visual afferentation to central visual areas is interrupted. Our findings in the MS of the LGN indicate that during the usual operation of REM sleep, central visual-sensory sites receive intrinsic activation that, in the visual system, is additive and complementary to the stimulation obtained from extrinsic sources. In the course of early development, normative symmetrical activation of central visual areas during REM sleep may counterbalance plasticity changes caused either by absent or aberrant sensory stimulation.

Serum concentrations of C-reactive protein (CRP), interleukin-6 (Il-6) and tumor necrosis factor-alpha (TNF-alpha), as well as body mass index (BMI) were measured in a series of 36 elderly subjects (18 males, 18 females) of mean age 76.8+/-4.5 years, in order to assess whether these parameters are involved in senile osteoporosis (SOP). Bone mineral density was determined, by a dual-emission X-ray absorbimetry (dexa) method on the nondominant radius, as a measure of SOP. These studies revealed the following main results: (i) the female/male ratio of SOP at this age is 4:1; (ii) overweight has a sort of protection against SOP in females; (iii) increased Il-6 and TNF-alpha serum levels when observed in either of the sexes were accompanied by SOP, indicating that these parameters may be involved in provoking and maintaining SOP; (iv) elevated serum CRP levels indicate, in most elderly subjects, the presence of inflammation in SOP which has been considered previously as a merely 'wear and tear'-induced disease.

The bone mineral density (BMD) has been analyzed in 200 male patients divided in 4 groups of age as follows: (A) 40-49, (B) 50-59, (C) 60-69, and (D) 70 years and above. BMD was measured by using the DEXA technique both in the ultradistal and mediodistal region of radius of the non-dominant side. In addition, the serum levels of testosterone (Ts), dihydrotestosterone (DHT) and 17-beta estradiol (E-2) have also been measured. The data obtained have shown that bone mineral density values are decreasing also in the males with advancing age, and the positive correlation (p < 0.05) of BMD with the E-2 levels also tend to decrease. These results suggest the hypothesis that the true sexual hormones regulating the rhythm of osteogenesis may be the estrogens in the males, too.

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine produces a parkinsonian syndrome in man and experimental animals. The toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1-methyl-4-phenylpyridinium, exhibits high-affinity uptake by plasma membrane monoamine transporters and also by the vesicular monoamine transporter. Using autoradiographic and immunohistochemical methods in mice, we demonstrate the accumulation of [3H]1-methyl-4-phenylpyridinium within neurons that contain the vesicular monoamine transporter, following systemic administration of [3H]1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Within 1-24 h following the intraperitoneal administration of 10 microg/kg of [3H]1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, [3H]1-methyl-4-phenylpyridine labelling was found within such regions as the locus coeruleus, dorsal, medial, and pallidal raphe nuclei, substantia nigra pars compacta, ventral tegmental area, and paraventricular nucleus of the hypothalamus. These regions all contain monoaminergic somata as defined by immunohistochemical staining with an antibody against the vesicular monoamine transporter. There was a positive relationship between the density of [3H]1-methyl-4-phenylpyridinium label and the density of vesicular monoamine transporter immunoreactivity: the highest densities of both were found in the locus coeruleus and lowest densities in the midbrain dopaminergic neurons. In addition, [3H]1-methyl-4-phenylpyridinium labelling was detected in the bed nucleus of the stria terminalis and paraventricular nucleus of the thalamus, which also contained vesicular monoamine transporter immunoreactive nerve terminals. The present data indicate that low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine cause a significant accumulation of 1-methyl-4-phenylpyridinium within monoaminergic somata in parallel with the amount of vesicular monoamine transporter in the neuron. Since nuclei with intense labelling are not damaged by doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine that are toxic to midbrain dopaminergic neurons, these data are consistent with the hypothesis that sequestration of 1-methyl-4-phenylpyridinium within monoaminergic synaptic vesicles can protect the neurons from degeneration caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

The neurotoxin MPTP has been used to create an animal model of Parkinson's disease in the mouse, in part, because it causes a significant loss of dopaminergic neurons in the substantia nigra (nucleus A9). The purpose of the present study was to determine whether MPTP also causes degeneration of midbrain dopaminergic neurons in nuclei A8 and A10 in the mouse, as occurs in humans with Parkinson's disease. Two commonly used strains of mice were used: FVB/N and C57BL/6. MPTP was administered in cumulative doses of 50-300 mg/kg. Seven days later, dopamine concentrations were measured in the striatum using high performance liquid chromatography, and midbrain dopaminergic neurons were identified using an antibody against tyrosine hydroxylase. The cell locations were mapped with a computer imaging system. In the FVB/N strain, there was a dose-dependent decrease in striatal dopamine concentrations. Although the highest dose (300 mg/kg) caused an 86% reduction in striatal dopamine concentrations, there was only a moderate and non-significant loss of midbrain dopaminergic neurons. In the C57BL/6 strain, however, a high dose of MPTP (240 mg/kg) caused a significant reduction in both striatal dopamine concentrations (95%), and midbrain dopaminergic cells; 69% loss of nucleus A8 cells, 75% loss of nucleus A9 cells, and in nucleus A10 subnuclei there was 42% loss of ventral tegmental area cells, 55% loss of interfascicular nucleus cells, and no loss of cells in the central linear nucleus. These data (1) provide further evidence for differential susceptibility to MPTP toxicity among different mouse strains, (2) indicate that a significant depletion of striatal dopamine is not necessarily due to degeneration of midbrain dopaminergic neurons, (3) provide the precise locations of midbrain dopaminergic cells that are vulnerable to MPTP, which will aid future studies that seek to determine the mechanism/s by which-MPTP selectively destroys only certain midbrain dopaminergic neurons, and (4) indicate that MPTP produces midbrain dopaminergic neuronal degeneration in the same nuclei in the C57BL16 mouse that degenerate in humans with Parkinson's disease.

The abundance of rapid eye movement (REM) sleep in the neonatal mammal and its subsequent decline in the course of development, as well as the dramatic and widespread enhancement of CNS activity during REM sleep, led us to propose that this state plays a functional role in the normative physiological and structural maturation of the brain [54]. When, after 1 week of monocular deprivation (MD), a second week of MD was coupled with behavioral deprivation of REM sleep, the structural alteration in the visual system provoked by MD alone (interlaminar relay cell-size disparity in the lateral geniculate nucleus (LGN) was amplified. With the addition of REM deprivation during MD, the LGN cells connected to the surgically patched eye, which are smaller than normal after MD, became even smaller, whereas the LGN cells receiving input from the seeing eye, which display compensatory hypertrophy after MD, grew even larger. We believe that the interlaminar disparity effect widened because during REM deprivation, the already vision-compromised LGN cells associated with the patched eye also lose the ascending brainstem activation reaching them during the REM state. Loss of the two main sources of 'afference' by these LGN cells permits their seeing-eye LGN counterparts to gain even greater advantage in the competition for synaptic connections in cortex, which is reflected in the relative soma sizes of the LGN relay cells. It is likely that the relatively abundant REM state in early maturation provides symmetric stimulation to all LGN relay cells, irrespective of eye of innervation. The symmetric activation propagated from brainstem to LGN acts to 'buffer' abnormal, asymmetric visual input and, thereby diminishes the extreme, asymmetric structural alteration that results from MD in the absence of REM sleep. We conclude that REM sleep-generated CNS discharge in development has the effect of 'protecting' the CNS against excessive plasticity changes. This is consistent with the possibility that REM sleep plays a role in the genetically programmed processes that direct normative brain development.

Objective: The authors compared clinical findings of Alzheimer's disease and the so-called Lewy body variant of Alzheimer's disease., Method: Available data were analyzed on the clinical features of 58 patients with Alzheimer's disease and 24 patients with the Lewy body variant of Alzheimer's disease who underwent postmortem examination., Results: The proportion of men was significantly larger in the Lewy body variant group than in the Alzheimer's disease group (66.7% versus 34.5%), and, concordantly, the Lewy body variant group was slightly taller. The prevalence of hallucinations and delusions was significantly higher in Lewy body variant subjects than the Alzheimer's disease subjects, but there were no significant differences between the two groups in educational attainment, family history of dementia, age at onset, duration of illness, cognitive impairment, overall severity of illness, or neuropsychological findings. Patients with the Lewy body variant of Alzheimer's disease tended to experience more frequent extrapyramidal side effects of neuroleptics than did the patients with Alzheimer's disease, but for patients in the two groups who were not exposed to neuroleptics, there was little difference in frequency of extrapyramidal side effects. CSF concentration of homovanillic acid (HVA) was significantly lower in the Lewy body variant patients, even when correction was made for height., Conclusions: The Lewy body variant of Alzheimer's disease may be suspected in elderly male dementia patients who otherwise meet criteria for Alzheimer's disease but who manifest significant psychiatric symptoms and neuroleptic-induced extrapy-ramidal side effects and have low levels of CSF HVA.

The calcium-binding protein calbindin-D28k (CALB) has been localized in high concentrations in several neuronal populations within the central nervous system (CNS) and is believed to act as an intracellular calcium (Ca2+) buffer. There has been much interest and speculation concerning its potential neuroprotective function. However, there is little direct evidence linking CALB content of individual neurons to Ca2+ buffering ability, resistance to Ca(2+)-mediated excitotoxicity, or vulnerability to Ca(2+)-mediated degeneration. It is necessary to demonstrate these relationships on a cellular level so that more definitive conclusions can be made. We have utilized immunocytochemical and Western blot techniques to determine whether cellular CALB content is altered in the nucleus A10 dopaminergic region of the midbrain following administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Our data demonstrate a significant increase in the CALB content of nucleus A10 neurons (up to 227 +/- 23% above control) 3 and 6 h after MPTP treatment. CALB elevation demonstrated both time and dosage dependence as 6-h groups exhibited larger increases than 3-h groups, and a 60 mg/kg dosage induced a larger increase than a 20 mg/kg dosage. These data support the hypothesis that MPTP is neurotoxic by causing increases in free intracellular Ca2+ and that increased CALB in the midbrain dopaminergic neurons is a protective response to elevated intracellular free Ca2+.

The biological function of REM sleep is defined in terms of the functions of neural processes that selectively operate during the REM sleep state. The high amounts of REM sleep expressed by the young during a period of central nervous system plasticity suggest that one function of REM sleep is in development. The phenomenon of activity-dependent development has been clearly shown to be one mechanism by which early sensory experience can affect the course of neural development. Activity-dependent development may be a ubiquitous process in brain maturation by which activity in one brain region can influence the developmental course of other regions. We hypothesize an ontogenetic function of REM sleep; namely, the widespread control of neuronal activity exerted by specific REM sleep processes help to direct brain maturation through activity-dependent developmental mechanisms. Preliminary tests of the hypothesis have been conducted in the developing feline visual system, which has long been known to incorporate information derived from visual experience in establishing neuronal connectivity. We find that suppression of REM sleep processes by an instrumental REM deprivation procedure results in a significant enhancement of the effects of altered visual experience by monocular occlusion. Bilateral brainstem lesions that selectively block the occurrence of ponto-geniculo-occipital (PGO) waves are sufficient to produce similar results. These data indicate that the propagation of phasic influences during REM sleep interacts with other processes subserving neural development. This source of influence appears not to derive from the environment but rather stems from an intrinsic source of genetic origin. Examination of the neural activity associated with PGO waves in the lateral geniculate nucleus reveals a distribution of facilitatory influence markedly different from that induced by visual experience. We conclude that REM sleep directs the course of brain maturation in early life through the control of neural activity.

Several lines of evidence indicate that an interaction exists between opioid peptides and midbrain dopaminergic neurons. The purpose of this study was to map and quantify the density of the mu opioid receptor subtype relative to the location of the dopaminergic (DA) neurons in the retrorubral field (nucleus A8), substantia nigra (nucleus A9), and ventral tegmental area and related nuclei (nucleus A10) in the rat. Sections through the rostral-caudal extent of the midbrain were stained with an antibody against tyrosine hydroxylase, as a DA cell marker, and comparable sections were processed for in vitro receptor autoradiography using the mu-selective ligand, 3H-Tyr-D-Ala-N-MePhe-Gyl-ol enkephalin. In the nucleus A8 region, there were low levels of mu binding. In the rostral portion of nucleus A9, there was prominent mu binding both in the ventral pars compacta, which contains numerous DA neurons, and in regions that correspond to the location of the DA dendrites which project ventrally into the underlying substantia nigra pars reticulata. In the caudal portion of nucleus A9, mu binding was greatest in the substantia nigra pars reticulata, but also in the same region that contains DA neurons. In nucleus A10, mu receptor densities differed depending upon the nucleus A10 subdivision, and the rostral-caudal position in the nucleus. Low receptor densities were observed in rostral portions of the ventral tegmental area and interfascicular nucleus, and there was negligible binding in the parabrachial pigmented nucleus and paranigral nucleus at the level of the interpeduncular nucleus; all regions where there are high densities of DA somata. Mu binding was relatively high in the central linear nucleus, and in the dorsal and medial divisions of the medial terminal nucleus of the accessory optic system, which has been shown to contain DA dendrites. These data indicate that mu opioid receptors are located in certain regions occupied by all three midbrain DA nuclei, but in a highly heterogeneous fashion.

Opiates and opioid peptides are known to influence the dopaminergic (DA) neurons in the midbrain. The purpose of this study was to map and quantify the density of kappa and delta opioid receptor subtypes in the retrorubral field, substantia nigra, and ventral tegmental area and related nuclei, which contain DA nuclei A8, A9, and A10, respectively. Sections through the rostral-caudal extent of the rat midbrain were stained with an antibody against tyrosine hydroxylase, as a DA cell marker, and comparable sections were processed for in vitro receptor autoradiography using the kappa-selective ligand, U-69593, and the delta-selective ligand, D-Pen2, D-Pen5-enkephalin. In general, both kappa and delta ligands exhibited low levels of specific binding in regions occupied by the midbrain DA neurons. Kappa binding (4-8 fmol/mg tissue) was high throughout the rostral-caudal extent of the substantia nigra, in rostral portions of the ventral tegmental area, and in the nucleus paranigralis; low binding occurred in the retrorubral field and central linear nucleus raphe. Delta binding (6-18 fmol/mg tissue) was high in the caudal portion of the substantia nigra pars reticulata, and in the medial terminal nucleus of the accessory optic system (a region previously shown to contain DA dendrites). The kappa and delta receptor binding is heterogeneously distributed in regions occupied by midbrain dopaminergic neurons, and several fold lower than the binding of mu opioid receptors in the same brain regions.

Several days after the administration of 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'CH3-MPTP) to the BALB/cJ mouse there is a loss of midbrain dopaminergic neurons, a reduction of forebrain dopamine (DA) content, and an elevation in forebrain DA turnover. The purpose of the present study was to determine whether the increase in forebrain DA turnover is related to an increase in dopaminergic neuronal activity. In vitro extracellular single unit recordings were made from midbrain dopaminergic neurons in the substantia nigra pars compacta (nucleus A9) and ventral tegmental area (nucleus A10) of BALB/cJ mice. The experimental animals were treated intraperitoneally with 40, 50 or 55 mg/kg 2'CH3-MPTP and killed 7-15 days later. Forebrain DA concentrations were decreased below control values by the two higher toxin doses in the caudate-putamen (67% and 78%, respectively), but not in the nucleus accumbens. DA turnover increased more than 2-fold in the caudate-putamen, but was unchanged in the nucleus accumbens. Nucleus A9 cells, in the 2'CH3-MPTP-treated animals, exhibited a 3-fold increase in the number of spontaneously active cells, and an 84% increase in basal firing rates. There was also a positive correlation between the A9 cell firing rates, and the DA turnover in the striatum of the toxin-treated mice. Nucleus A10 cells, in the 2'CH3-MPTP-treated animals, exhibited neither changes in number of spontaneously active cells nor changes in firing rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Both alpha 2-adrenergic (alpha 2) and serotonergic (5HT) neurons are associated with stimulation of GH secretion via GRH release. The object of this study was to determine whether the 5HT system is involved in the stimulation of GH secretion by alpha 2-receptor agonists. There are two parts of this study. In the first, the relationship between alpha 2-5HT systems were analyzed by determining if alpha 2-stimulated GH release is mediated by 5HT. In this model, systemically administered alpha 2-agonists [clonidine (CLON) or UK14,304] were tested against 5HT antagonists (meterogoline or cyproheptadine) or 5HT synthesis inhibitors (p-chlorophenylalanine methylester hydrochloride). In the second, sites of 5HT-GRH interaction were determined by testing the response to CLON after 5HT neurotoxin [5,7-dihydroxytryptamine (5,7-DHT)] microinjection at specific hypothalamic nuclei. In both experiments sequential blood samples were withdrawn from silastic jugular cannulas in unanesthetized, freely moving animals. Metergoline (0.045 and 0.135 mg/kg, iv) and cyproheptadine (0.969 micrograms/kg, iv) suppressed, in a dose-dependent manner, the CLON (33 or 66 micrograms/kg, iv)-induced GH surge that was detected 15-30 min after injection in control animals. Both cyproheptadine (0.969 micrograms/kg, iv) and p-chlorophenylalanine (300 mg/kg, ip) effectively suppressed the UK14,304 (220 micrograms/kg, iv)-induced GH surge that occurred 15-30 min after injection in control animals. These data suggest that an intact 5HT system is required for alpha 2-stimulated GH release. 5,7-DHT neurotoxin microinjected into the midline arcuate nucleus (6 micrograms/mg,iv) or bilaterally into the ventromedial nucleus or perifornical area (4 micrograms/0.2 microliter) 5 days previously suppressed the CLON (30 micrograms/kg)-induced GH surge only in animals with arcurate nucleus lesions. To determine if the suppression was mediated by inhibition of GH-releasing hormone (GRH) or stimulation of somatostatin (SRIF), an additional experiment was conducted including 5,7-DHT arcuate nucleus-lesioned animals injected with anti-SRIF. Inasmuch as anti-SRIF failed to reverse the 5,7-DHT suppression of GH secretion, the results of this experiment suggest that GRH mediates NE-5HT-induced GH secretion. In conclusion, these data suggest that alpha 2 activation of GH secretion requires intact serotonergic terminals in the arcuate nucleus and most likely involves GRH rather than SRIF, release.

A technique for embryonic implantation and the subsequent recording of electrocortical, neck muscle, and ocular activity continously from the 20th day of incubation through hatching and the first few days thereafter is demonstrated. The embryonic maturation of the EEG, with a characteristic muscle burst pattern heralding hatching was found, supporting previous reports obtained with acute preparations. The technique for injection into the chorioallantoic membrane (CAM) vessels or direct deposition onto the CAM is also described. The usefulness of the embryonic neurophysiological implantation coupled with the injection at specific stages of development is discusses as an approach to the understanding of the parameters of the maturation of the sleep-wakefulness cycle, neurochemistry, and behavior.

The intracortical distribution of monoamines, noradrenaline (NA) and serotonin (5-HT), was examined in the visual cortex of the rat with high pressure liquid chromatography (h.p.l.c.) and radioautography. H.p.l.c. measurements showed the densities of both amines to be highest in layer I. The concentration of NA varied considerably in all other layers while the 5-HT concentration decreased with increasing distance from the pial surface. The morphological characteristics of the monoaminergic axon-terminals in the cerebral cortex has been the subject of controversy in recent years. We have used radioautography following topical or intraventricular administration of tritiated amines to examine the ultrastructural features of these terminals in the visual cortex of the rat. Systematic analysis of single sections revealed that more than one-half of the terminals labelled with tritiated NA or 5-HT formed typical synaptic contacts (mostly type I) with dendritic shafts or spines.

The plasma concentrations of dopamine in blood from hypophysial portal vessels in various locations on the pituitary stalk were evaluated in diestrous rats. It was found that the mean concentration of dopamine in blood from lateral hypophysial portal vessels, which contain the venous effluent of the lateral median eminence, was significantly less (P less than 0.005) than that in blood from medial portal vessels, which contain the venous effluent of the medial median eminence [1.59 +/- (SE) 0.23 ng/ml vs. 3.12 +/- 0.48 ng/ml]. The mean plasma concentration of dopamine in blood of lateral portal vessels and of medial portal vessels was at least 20-40 times greater than that in arterial blood of these animals. It was calculated that the rate of release of hypothalamic dopamine was 174 +/- 38 pg/h into a medial portal vessel and 73 +/- 15 pg/h into a lateral portal vessel. The mean plasma concentration of norepinephrine or epinephrine in blood from a medial portal vessel was not different from that from a lateral portal vessel. To address the issue of whether the rate of release of dopamine into a medial portal vessel and into a lateral portal vessel was correlated with the rate of synthesis of dopamine in discrete regions of the median eminence, the concentration of L-dihydroxyphenylalanine (DOPA), the precursor of dopamine, was evaluated in lateral and medial segments of the median eminence of diestrous rats treated with 3-hydroxybenzylhydrazine, an inhibitor of DOPA decarboxylase activity. The concentration of DOPA was similar in the medial and lateral segments of the median eminence, suggesting that the rate of synthesis of dopamine did not account for the difference in the rate of release of dopamine into portal blood. The finding of different concentrations of dopamine in blood from various hypophysial portal vessels may be important in view of the heterogenous perfusion of the pars distalis with hypophysial portal blood. We suggest that topographic differences may exist in the release of PRL by cells of the pituitary gland as a consequence of uneven concentrations of dopamine in portal blood perfusing the lactotropes.

The present study examined whether neostriatal monoamine biochemistry was activated in a bilaterally symmetrical fashion during a non-lateralized forward locomotor task, and whether specific midbrain dopamine (DA) neuronal systems were influenced selectively by specific behavioral tasks. Monoamine concentrations (DA, serotonin and their metabolites) were measured, using high pressure liquid chromatography, in the neostriatum, nucleus accumbens, and medial prefrontal cortex in rats that were either induced to walk forward in a motorized rotating wheel (two speeds) or were exposed to footshock stress (two shock intensities). Our results demonstrate that during locomotor behavior there is an increase in neostriatal DA metabolism, but not in serotonin metabolism. Furthermore, the increase in DA metabolism was found: (a) in both right and left neostriatal nuclei, but with significantly less asymmetry than occurred in non-locomoting control rats; and (b) within the neostriatum at both speeds and also in the nucleus accumbens at the higher speed. Locomotion had no effect on DA metabolism in the prefrontal cortex. With both shock intensities there was increased DA metabolism in the prefrontal cortex, whereas during the low shock intensity there was also an increased DA metabolism in the nucleus accumbens. At the high level of footshock, which evoked jumping and running escape behavior, there was also an increase in neostriatal DA metabolism. These data indicate that a non-lateralized forward locomotor task activates DA metabolism primarily in the less metabolically active hemisphere. Secondly, we found that specific subgroups of midbrain DA neurons can be selectively activated by specific behavioral tasks.

The effects of apomorphine (Apo), haloperidol (Hal), reserpine, phenyoxybenzamine, oxotremorine and scopolamine on hypothalamic caatecholamines and metabolites were assessed. All these drugs, except Apo, significantly changed the hypothalamic concentration of 3-methoxy-4-hydroxyphenylglycol (MHPG), thus suggesting parallel changes in noradrenaline (NA) metabolism and turnover. Hal increased MHPG, an effect which was reversed by Apo pretreatment. Oxotremorine and scopolamine respectively increased and decreased MHPG, reserpine decreased NA and increased MHPG. Phenoxybenzamine increased MHPG without altering NA concentrations. Dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were not changed by Apo and Hal, but were influenced by the other drugs. These results indicate that NA in the hypothalamus is influenced by both cholinergic and dopaminergic events occurring in the brain and that dopaminergic neurones in this organ are different in their biochemical and pharmacological characteristics from neurones present in other central and peripheral systems.