Improvement of control cable system of trans-humeral body-powered prostheses.

For the purpose of improving the efficiency of a body-powered prosthesis, a control cable system was developed which uses a pulley and a cable housing which includes a highly slippery plastic liner. Improvements were also made to the harness. In this paper, the mechanism of these systems is firstly described and then, the results of a clinical evaluation test of a practical model is presented along with an efficiency evaluation by a testing instrument. For the design of each system, the material and size suitable for the conditions of cosmetic and general versatility were considered. The clinical test was performed on 12 subjects to prove the effectiveness of the system. This test procedure was repeated. These tests proved the effectiveness of the systems.

Decreased expression of the mRNA for somatostatin in the periventricular nucleus of depression-model rats.

Expression of the mRNA for somatostatin (SRIF) in the periventricular nucleus (PeN), the level of SRIF in the stalk-median eminence (SME) and the concentration of growth hormone (GH) in the plasma were examined in depression-model rats in an attempt to confirm the hypothesis that SRIF neurons in the hypothalamus are hypofunctional in this model. We exposed male Wistar rats to intermittent walking stress for two weeks and then we measured their spontaneous running activity for 12 days. We divided the rats into a depression-model group and a partial-recovery group according to the spontaneous running activity of each rat after the termination of exposure to stress. Expression of SRIF mRNA in the PeN of the hypothalamus was monitored by in situ hybridization and relative levels were determined with an image analysis system. The relative level of expression of SRIF mRNA in the PeN was lower in rats in the depression-model group than in the control group and the partial-recovery group. The level of SRIF in the SME was lower and the plasma concentration of GH was higher in the depression-model group than in the other groups. Our findings suggest that reduced expression of mRNA for SRIF in the PeN might be associated with the pathophysiology of rats with this particular model of depression.

Increased expression of magnocellular arginine vasopressin mRNA in paraventricular nucleus of stress-induced depression-model rats.

Exposure of rats to long-term intermittent walking stress results in a persistent inactive behavior in the subsequent two weeks in about 50% of rats (depression-model rats) while the activity returns gradually toward baseline in other rats (spontaneous recovery rats). To explore the role of hypothalamic-pituitary-adrenal (HPA) axis in these depression-model rats, we examined changes in the gene expression of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) in the paraventricular nucleus (PVN) of the hypothalamus using in situ hybridization histochemistry. We imposed the intermittent walking stress for two weeks in male Wistar rats, then compared the response of the depression-model rats and spontaneous recovery rats. The expression of CRF mRNA in PVN increased significantly by 60% and 80% compared to controls, in the model and the recovery rats, respectively. The magnocellular AVP mRNA in PVN increased significantly in the model rats by 60% compared to controls. The concentration of plasma ACTH increased in the model rats, but no significant change in plasma corticosterone or AVP level was noted in all three groups. Our results suggest that increased magnocellular AVP in PVN plays an important role in the regulation of HPA axis of the depression-model rats induced by long-term walking stress.

Tyrosine hydroxylase gene expression in the locus coeruleus of depression-model rats and rats exposed to short-and long-term forced walking stress.

Abnormal brain noradrenergic function is thought to cause depressive illnesses which are sometimes manifested or aggravated under stressful conditions. To investigate the effect of chronic stress on noradrenaline (NA) synthesis in the brain we used in situ hybridization to examine the expression of tyrosine hydroxylase (TH) mRNA in the locus coeruleus (LC) of "depression-model rats" that exhibit reduced activity following exposure to long-term (14 days) forced walking stress (FWS). We also examined TH mRNA expression in rats stressed for 30 minutes, 3 hours and 1, 2 (short-term), 6 or 12 (long-term) days. The expression of TH mRNA increased markedly following 1 to 12 days of FWS, but not in rats exposed to FWS for 30 minutes or 3 hours. The expression also increased significantly in the depression-model rats, but not in the "spontaneous recovery rats" whose activity was restored after long-term stress. Our results suggest that NA synthesis remains high in the FWS-induced depression-model rats because of the high levels of TH mRNA expression in the LC. Our results also suggest that FWS is initially a mild stress but gradually becomes a severe form of unadaptable stress as reflected by delayed but persistent increases in TH mRNA expression.

Effect of reserpine on 3-methoxy-4-hydroxyphenylethyleneglycol and 3,4-dihydroxyphenylacetic acid in the hippocampus of depression-model rats: an in vivo microdialysis study.

Using in vivo microdialysis, we examined the effect of intraperitoneal injection of reserpine (2 mg/kg) on hippocampal 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and 3,4-dihydroxy-phenylacetic acid (DOPAC), two major metabolites of catecholamine. Responses were examined serially for 12 h in the hippocampus of walking-stress-induced depression-model rats, recovery rats and control rats. Control rats showed a rapid rise followed by a gradual fall of free and total MHPG and a delayed increase of DOPAC in response to reserpine. Depression-model rats showed a significantly blunted biphasic response of free and total MHPG as well as blunted monophasic response of DOPAC compared with control rats. Recovery rats also exhibited a blunted fall response of MHPG. Our findings suggest that the vesicle membrane in the central noradrenaline (NA) neurons could be hyposensitive to reserpine in the depression-model rats.

Enhanced response of growth hormone to growth hormone-releasing hormone and a decreased content of hypothalamic somatostatin in a stress-induced rat model of depression.

This study was designed to evaluate changes in the hypothalamic somatostatin-growth hormone axis (SRIF-GH axis) in a stress-induced rat model of depression. We exposed male Wistar rats to intermittent walking stress for two weeks, and then measured their spontaneous running activities for 12 days. We divided the rats into the depression-model group and the partial recovery group according to their spontaneous running activities after the termination of exposure to stress. We examined the secretion of GH from the anterior pituitary by injecting human GH-releasing hormone (hGHRH) with intracardiac cannulae or by applying hGHRH or SRIF to isolated anterior pituitaries using a perifusion system. We also determined SRIF content in the stalk-median eminence (SME) and the plasma concentration of GH. In the depression-model group, intracardiac administration of hGHRH caused the enhanced release of GH into plasma, while application of hGHRH or SRIF to the anterior pituitary in vitro had similar effects on GH release in the control and partial recovery groups. Furthermore, the SRIF content was decreased in the SME and the GH concentration was increased in plasma. The partial recovery group gave similar values to the control group. The enhanced response of GH to hGHRH in the depression-model group might have been caused by the reduced content of SRIF in the SME in view of the unchanged response of GH to the infusion of hGHRH or SRIF in the perifusion system.

EEG findings in diabetic patients with and without retinopathy.

OBJECTIVES: We showed previously that temporal low-voltage irregular delta waves (TLID) on EEG are indicative of cerebrovascular dysfunction in its early stages. The present study was designed to determine whether the incidence of this finding is elevated in diabetics as compared to normal controls. METHODS: EEGs of 50 diabetics and 50 normal controls were examined. Relationships of blood sugar levels, levels of HbA1C and stages of diabetic retinopathy to TLID were also examined. RESULTS: TLID was found in 56% of EEGs of the diabetics and in 14% of EEGs of the controls (P < 0.0001). The occurrence of TLID was also associated with the presence of diabetic retinopathy. CONCLUSIONS: Our results suggest that the incidence of cerebrovascular dysfunction is elevated in diabetics. Since TLID was associated with diabetic retinopathy, it seems possible that the TLID detected in diabetics might reflect certain functional changes induced by microangiopathy of the brain.

Long-term stress degenerates, but imipramine regenerates, noradrenergic axons in the rat cerebral cortex.

Exposed to a forced walking stress for 2 weeks, some rats became persistently inactive (depression-model rats), whereas others gradually recovered from exhaustion (spontaneous recovery rats). We also studied rats exposed to short-term stress, rats without stress, and the model rats treated with imipramine or saline. We examined the density of noradrenergic axons in the frontal cortex using retrograde labeling of the locus coeruleus with horseradish peroxidase injected into the cortex and immunohistochemical staining of cortical axons with dopamine beta-hydroxylase antiserum. The density was significantly lower in the depression-model rats, but tended to be higher in the recovery rats and short-term stressed rats. Chronic treatment with imipramine significantly increased the density in the model rats. There was also a correlation between the density of noradrenergic axons and the recovery rate of activity. Our results suggest that cortical noradrenergic degeneration is involved in the pathogenesis of depression.

Degeneration of locus coeruleus axons in stress-induced depression model.

Antidepressants such as desipramine induce axonal regeneration of brain noradrenergic neurons. This novel action of antidepressants suggests the involvement of degeneration or retraction of brain noradrenergic axons in the pathophysiology of clinical depression. The present study was designed to further confirm this view in an animal model of stress-induced depression. The depression model was produced by exposing rats to prolonged forced walking stress. To see if axonal degeneration of noradrenergic neurons occurred in the depression model, the density of noradrenergic axons in the cerebral cortex was assessed by three different methods, antidromic stimulation technique, retrograde tracing with horseradish peroxidase and immunohistochemical staining with dopamine-beta-hydroxylase antiserum. These methods all assured of degenerative changes of noradrenergic axon terminals in the depression model. Furthermore, it was found that repeated treatments of the depression-model rats with imipramine could cause regeneration of cortical noradrenergic axons. These findings support the view that degeneration or retraction of noradrenergic axons is involved in the pathophysiology of depression.

Electrophysiological evidence for axonal degeneration of locus coeruleus neurons following long-term forced running stress.

Using electrophysiological methods, a change in the density of axon terminals of locus coeruleus (LC) neurons in the cerebral cortex of rats following long-term forced running stress was examined. The stressed animals were classified into two groups based on spontaneous running activity (SRA) measured for 2 weeks after the stress treatment: 1) animals showing early restoration of SRA (poststress active rat) and 2) animals showing little or no SRA (poststress inactive rat). To quantify the density of LC axon terminals in the cerebral cortex, the percentage of LC neurons antidromically activated by cortical stimulation (projection index, P-index) was assessed. The P-indices for the cortex decreased in the poststress inactive rats. Since the threshold currents for antidromic activation were not altered by the stress treatment, the observed change was considered to reflect a change of the density of LC axon terminals rather than physiological consequences. Therefore, when animals receive a prolonged, severe stress, LC neurons in a certain group of the animals may cause axonal retraction or degeneration in the cerebral cortex.

Tyrosine hydroxylase activity in discrete brain regions of depression model rats.

Tyrosine hydroxylase (TH) activity was measured in discrete brain regions of rats during short-term forced running stress (FRS). TH activity was also determined in a depression-like state and in a recovered state after a long-term FRS. Under the short-term FRS, the TH activity showed a significant increase in the locus ceruleus, certain limbic regions and tuberoinfundibular system. In the depression-like state, however, there was a significant decrease in the locus ceruleus and certain limbic regions, but a significant increase was seen in the median eminence. The TH activity in recovered rats showed no difference from the level in the controls. These findings demonstrate an adaptive increase in the TH activity in relation to stress, and may also indicate a failure of adaptation in the depression-like state.

Pure word deafness with possible transfer of language dominance.

A 55-year-old, right-handed male patient with a past history of a stroke followed by a difficulty of speech and hearing fell and manifested a left hemiplegia. He could neither comprehend spoken language and melody nor repeat them, though he spoke with paraphasia and understood written language and nonverbal sound. An electroencephalogram, pneumoencephalogram and cerebral angiogram suggested the existence of old infarcts in the left temporal lobe and a probable new one in the right cerebrum. A diagnosis of this case was made as pure word deafness which might be caused by a reimpairment of the language function possibly transferred to the nondominant, right hemisphere following the early stroke.

Chronic immobilization stress: evidence for decreases of 5-hydroxy-tryptamine immunoreactivity and for increases of glucocorticoid receptor immunoreactivity in various brain regions of the male rat.

Male rats were exposed to severe 14 day immobilization stress. Body weight, body temperature, food and water intake, behavioral parameters, and serum corticosterone levels were measured during and after the stress period. On the 7th day after cessation of stress the experimental animals together with the control rats were taken to immunocytochemical analysis involving morphometry and microdensitometry of tyrosine hydroxylase (TH), 5-hydroxytryptamine (5-HT), various neuropeptide, and glucocorticoid receptor (GR) immunoreactivities (IRs) in a large number of regions of the central nervous system. In addition, adrenocorticotropic hormone (ACTH) IR was analyzed in the pituitary gland. Seven days following cessation of the chronic stress food intake, total locomotion and forward locomotion had been restored to normal. Serum corticosterone levels appeared to remain increased even 6 days following cessation of the chronic immobilization stress, probably caused by increased release of ACTH. Paraventricular corticotropin releasing hormone (CRF) IR was negatively correlated with the pituitary ACTH IR, indicating that the increase in ACTH release was produced by an increased release of CRF from the hypothalamus. The major immunocytochemical change observed 7 days after cessation of stress was a disappearance of 5-HT IR in the 5-HT cell groups B1, B2, B3, and B7. 5-HT IR in nerve terminals was only affected in the dorsal horn, where 5-HT IR was increased in the substantia gelatinosa. GR IR was found to be significantly increased in monoaminergic cell groups: serotoninergic B7, dopaminergic A12, and noradrenergic A1, A2, and A6. A trend for a reduction of TH IR was observed in nigral DA cells associated with significant reductions in TH IR in striatal DA nerve terminals. Finally, increases in 5-HT and substance P (SP) IR were found in the nerve terminals of the substantia gelatinosa of the cervical spinal cord in the stress group. In the present experimental model evidence has been obtained for a maintained activation of the hypothalamic-pituitary-adrenal axis as evaluated 7 days after cessation of severe chronic immobilization stress. The reduction of 5-HT IR in various 5-HT cell groups indicates a reduction of 5-HT synthesis, which may also be associated with reduced 5-HT release from the nerve terminals, since no depletion was observed in terminal regions and in one case an increase in 5-HT IR was noted (substantia gelatinosa).(ABSTRACT TRUNCATED AT 400 WORDS)

Chronic nicotine treatment counteracts the disappearance of tyrosine-hydroxylase-immunoreactive nerve cell bodies, dendrites and terminals in the mesostriatal dopamine system of the male rat after partial hemitransection.

Male Sprague-Dawley rats were partially hemitransected at the mesodiencephalic junction and treated with nicotine (nicotine hydrogen (+)-tartrate) using Alzet minipumps implanted subcutaneously. Nicotine was delivered for 2 weeks in a dose of 0.125 mg/kg/h resulting in a serum nicotine level of 50.0 +/- 5.1 ng/ml. Three other groups of rats were analyzed: hemitransected rats receiving saline treatment and sham-operated animals receiving nicotine and saline, respectively. The effects of hemitransection and nicotine rostrally as well as caudally to the lesion were evaluated with image analysis of tyrosine hydroxylase (TH)-immunoreactive (IR) nerve cell body and dendrite profiles in the rostral and caudal substantia nigra and of TH-IR nerve terminal profiles in the striatum. Adjacent sections were taken to Nissl staining. [3H]Nicotine binding in the midbrain and forebrain was studied by means of receptor autoradiography on partially hemitransected rats receiving no treatment. Catecholamine (CA) levels in the frontal cortex were measured using high-performance liquid chromatography (HPLC). Striatal dopamine (DA) function was analyzed studying apomorphine-induced (1.0 mg/kg) ipsilateral rotational behavior. The spontaneous behavior of the rats was evaluated with a hole board. Furthermore, body temperature and body weight were measured. The results demonstrated a lesion-induced disappearance of TH-IR cell body and dendrite profiles in the substantia nigra and of TH-IR nerve terminal profiles in the striatum. Similar findings were seen after Nissl staining. A significant counteraction of this disappearance was found in the nicotine-treated animals. On the lesioned animals a marked reduction of [3H]nicotine binding in the striatum and the substantia nigra was found. In the functional experiments an enhancement of the apomorphine-induced ipsilateral rotational behavior was demonstrated. The degree of rotation was positively correlated with the serum nicotine level. The study on spontaneous activity in the hole board showed a slower restoration of total activity in the hemitransected nicotine-treated rats. All these results are compatible with the hypothesis that the protective action of nicotine on the mesostriatal DA system may be due to a desensitization of excitatory nicotine cholinoceptors located on the nigral DA nerve cells, leading to a reduction of firing rate and reduced energy demands. Such an action of nicotine could be of importance for a possible anti-parkinsonian effect.

Effects of chronic imipramine treatment on glucocorticoid receptor immunoreactivity in various regions of the rat brain. Evidence for selective increases of glucocorticoid receptor immunoreactivity in the locus coeruleus and in 5-hydroxytryptamine nerve cell groups of the rostral ventromedial medulla.

Glucocorticoid receptor (GR) immunoreactivity (IR) was analyzed semi-automatically in the forebrain and in the lower brain stem of male rats treated for two weeks with imipramine (10 mumol/kg). Serum corticosterone and aldosterone levels were determined by means of radioimmunoassay procedures. The microdensitometric analysis demonstrated a selective increase in the GR IR in the nerve cell nuclei of the locus coeruleus (A6), of the ventral part of the reticular gigantocellular nucleus (B3L) and of the nucleus raphae magnus (B 3 M), whereas a small reduction of GR IR was found in the nucleus raphe obscurus (B2). In the morphometric analysis significant increases in the mean profile area of nuclear GR IR, which may be secondary to the increase in GR IR, were observed in the B 3 M. The serum corticosterone and aldosterone levels were not found to be significantly altered. The selective changes of GR IR may reflect the presence of an altered number of GR in these nerve cell groups and/or an altered translocation of GR to the nuclei. It is of substantial interest that these changes were observed in the presence of unchanged serum levels of corticosterone and aldosterone. It seems possible that adaptive changes in monoamine synapses induced by the chronic imipramine treatment may be responsible for the changes in GR IR found in the noradrenaline (NA) and 5-hydroxytryptamine (5-HT) cell bodies, respectively. The present results open up the possibility that chronic imipramine treatment may help to maintain the glucocorticoid receptor function in the locus coeruleus and in the 5-HT cell groups of the rostral ventromedial medulla of depressed patients.

Effect of antidepressant on behavior and central catecholamine of depression-model rats.

Effect of antidepressant on behavior and central catecholamine were investigated in depression-model rats produced by long-term forced running stress. Changes in the spontaneous running activity and the concentration and turnover of catecholamine were examined in non-stressed rats injected with saline and depression-model rats injected with saline, imipramine and MOD-20 (a candidate for a tetracyclic antidepressant). Running activity was significantly restored by injection of imipramine and MOD-20. In depression-model rats, the concentrations of central catecholamine increased in the cell bodies and nerve terminals of the ascending noradrenaline system, and turnover rates of the catecholamine decreased in the terminal region. The increased concentrations were returned to the non-stressed level after injection of the drugs. However, decreased turnover rates were not recovered after the injection. These results suggested that MOD-20 was a potent antidepressant and the therapeutic efficacy of antidepressants might be due to the restoration of catecholamine concentrations.

Evidence for discrete alterations in central cardiovascular catecholamine and neuropeptide Y immunoreactive neurons in aged male rats and in genetically hypertensive male rats of the Lyon strain.

A computer-assisted morphometrical and microdensitometrical analysis has been performed on cardiovascular noradrenaline (NA), adrenaline (A) and neuropeptide (Y (NPY) neurons in adult and 24-month-old male rats and on hypotensive (LL), normotensive (LN) and hypertensive (LH) male rats of the Lyon strain using the indirect immunoperoxidase procedures. It was found that in NPY/phenylethanolamine-N-methyltransferase (PNMT) costoring neurons of the CI area of the rostral medulla oblongata NPY-like immunoreactivity showed a more marked reduction than the PNMT immunoreactivity. Furthermore, within the parvocellular part of the paraventricular hypothalamic nucleus. NPY immunoreactive nerve terminal profiles were much more affected than the PNMT immunoreactive profiles during aging as revealed by a marked reduction in the number of profiles and by a marked reduction of absorbency values in the microdensitometrical analysis. Thus, in the NPY/PNMT costoring neurons of the A C1 group of the ventrolateral medulla projecting, for example, to the hypothalamus, the peptide transmission line may have a special vulnerability to the aging processes which may contribute to the development of hypertension in old people in view of a vasodepressor role of many central NPY/PNMT neurons. An extensive morphometrical and microdensitometrical analysis of the various catecholamine (CA) cell groups of the medulla oblongata of the LL, LN and LH rats of the Lyon strain was performed. In a comparison between LL and LH rats the A2 cell group of the LH strain showed a trend for an increase in the mean tyrosine hydroxylase (TH) immunoreactive cell body area and the C3 group showed a significant increase in the number of PNMT immunoreactive profiles.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of acute and chronic treatment with imipramine on 5-hydroxytryptamine nerve cell groups and on bulbospinal 5-hydroxytryptamine/substance P/thyrotropin releasing hormone immunoreactive neurons in the rat. A morphometric and microdensitometric analysis.

Groups of male rats were treated for a period of 14 days with imipramine (10 mumol/kg) given twice daily. Separate groups of rats received a single dose treatment using the same dose and experimental design as for the repeated treatment. Employing the avidin-biotin immunoperoxidase technique for immunohistochemistry 5-hydroxytryptamine (5-HT)-, substance P(SP)- and thyrotropin releasing hormone (TRH)-like immunoreactivities (IRs) were visualized in consecutive coronal sections of the brain stem and of the spinal cord. The IRs were studied by means of morphometric and microdensitometric procedures using automatic image analysis on profiles representing nerve terminal networks of the ventral horn of the cervical and lumbar enlargements of the spinal cord as well as their coexistence (5-HT/SP and 5-HT/TRH). With the same technique 5-HT IR was measured in the 5-HT nerve cell groups of the medulla oblongata (B1, B2, B3) and of the nucleus raphe dorsalis (B7) of the midbrain. In addition 5-HT and 5-hydroxyindolacetic acid (5-HIAA) levels were measured in the ventral and dorsal horns of the cervical and lumbar enlargements of the spinal cord using high performance liquid chromatography (HPLC). In the same parts of the spinal cord SP IR was studied by means of radioimmunoassay (RIA). The microdensitometric studies showed that chronic, but not acute, imipramine treatment selectively increased SP IR in the 5-HT/SP/TRH costoring nerve terminals of the medial part of the ventral horn in both the cervical and the lumbar enlargements. Furthermore, quantitative analysis of the entity of coexistence in the 5-HT nerve terminals networks of these areas showed that all the 5-HT nerve terminals contained SP and TRH IRs and that this phenomenon remained after acute and chronic imipramine treatment. The microdensitometric studies on the 5-HT nerve cell groups of the medulla oblongata and of the nucleus raphe dorsalis demonstrated that chronic, but not acute, imipramine treatment selectively increased 5-HT IR in the nerve cell bodies of the lateral part of group B3 as evaluated from the median grey values. Acute, but not chronic, imipramine treatment significantly increased the field area of 5-HT IR of nerve cell bodies in group B7, reflecting an increase in the mean profile area of the 5-HT IR nerve cell body profiles. Instead, the mean profile area of 5-HT IR cell bodies of group B1 was acutely reduced by imipramine.(ABSTRACT TRUNCATED AT 400 WORDS)

Intracisternal administration of cholecystokinin-8 counteracts the central cardiovascular effects of adrenaline and NPY. A study based on the coexistence of cholecystokinin, phenylethanolamine N-methyltransferase and neuropeptide Y immunoreactivity in neurons of the nucleus tractus solitarius.

(1) In the present study the occlusion method was employed to evaluate the overall coexistence of neuropeptide Y and phenylethanolamine-N-methyl transferase, neuropeptide Y and tyrosine hydroxylase as well as cholecystokinin and phenylethanolamine-N-methyl transferase immunoreactivity in nerve cell bodies of the dorsal subnuclei of the nucleus tractus solitarius of the male rat. A high degree of coexistence was established for neuropeptide Y/phenylethanolamine-N-methyl transferase, cholecystokinin/phenylethanolamine-N-methyl transferase and for tyrosine hydroxylase/neuropeptide Y immunoreactivity. (2) Sulfated [(12)I]cholecystokinin-8 was used as radioligand to study the densities of cholecystokinin-8 binding sites in the dorsal medulla oblongata by means of quantitative receptor autoradiography. High densities of binding sites were observed in parts of the nucleus tractus solitarius and in the area postrema. Labeling was also observed in the dorsal motor nucleus of the vagus. (3) In the physiological studies adrenaline (0.15-1.0 nmol), neuropeptide Y (0.075-0.75 nmol) and sulfated cholecystokinin-8 (0.3-3.0 nmol) were administered alone or in combination with neuropeptide Y or adrenaline intracisternally into ?-chloralose anaesthetized male rats. Especially the hypotensive and bradycardic responses of adrenaline were counteracted in the adrenaline/cholecystokinin co-treated animals, whereas the cardiovascular effects of neuropeptide Y when co-administered with cholecystokinin-8 (0.3 nmol) appeared to be more resistant to the antagonistic effect of cholecystokinin 8. In addition, cholecystokinin-8 further enhanced the neuropeptide Y-induced bradynpnea and increase in the tidal volume. The present results indicate the existence of neuropeptide Y, adrenaline and cholecystokinin-8 immunoreactivity in the same neurons of the dorsal subnuclei of the nucleus tractus solitarius. Furthermore, binding sites for cholecystokinin-8 seem to at least partly co-distribute with ?-2 adrenergic and neuropeptide Y binding sites in the nucleus tractus solitarius. In the functional analysis, an antagonistic interaction between cholecystokinin-8 and adrenaline as well as between cholecystokinin and neuropeptide Y is demonstrated opening up the possibility that cholecystokinin peptides act as intrinsic modulators in the putative cholecystokinin/neuropeptide Y/adrenaline synapses in the nucleus tractus solitarius.