Enhancement of rapid eye movement sleep in the rat by actions at A1 and A2a adenosine receptor subtypes with a differential sensitivity to atropine.

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 leptin, a new hormone of adipose tissue: clinical findings and perspectives in geriatrics.

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).

Alendronate reduces the daily consumption of insulin (DCI) in patients with senile type I diabetes and osteoporosis.

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.

Food restriction-like effects of dietary dehydroepiandrosterone. Hypothalamic neurotransmitters and metabolites in male C57BL/6 and (C57BL/6 x DBA/2)F1 mice.

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.

Correlation between the bone mass, psychometric performances, and the levels of autonomy and autosufficiency in an elderly Italian population above 80 years of age.

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.

A new method for diagnosing fever of unknown origin (FUO) due to infection of muscular-skeletal system in elderly people: leukoscan Tc-99m labelled scintigraphy.

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.

Leukoaraiosis, cognitivity and affectivity in elderly patients: on the lack of correlations between neurodiagnostic and psychometric findings.

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.

Use of alendronate in treatment of secondary osteoporosis from hypopituitarism: a case report.

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.

Ponto-geniculo-occipital-wave suppression amplifies lateral geniculate nucleus cell-size changes in monocularly deprived kittens.

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.

Thyroid hormones and lipid metabolism in a group of patients over seventy.

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.

Electroionotherapy in acute arthrorheumatic pain.

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.

The NTX assay in the follow-up of the osteoporotic patients: 3 years of alendronate treatment.

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.

Assessment of cognitive and affective disorders in an elderly population undergoing hemodialysis.

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.

The neurotoxin 1-methyl-4-phenylpyridinium is sequestered within neurons that contain the vesicular monoamine transporter.

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.

REM sleep deprivation in monocularly occluded kittens reduces the size of cells in LGN monocular segment.

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.

Correlations between C-reactive protein, interleukin-6, tumor necrosis factor-alpha and body mass index during senile osteoporosis.

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.

Estrogens and euosteogenesis in men.

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 MPTP causes degeneration of specific nucleus A8, A9 and A10 dopaminergic neurons in the mouse.

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.