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K Fuxe

Publications and source records attributed to K Fuxe.

At least 379 records · Page 21Linked to original sources
PubMed1989

Neurotensin counteracts apomorphine-induced inhibition of dopamine release as studied by microdialysis in rat neostriatum.

Microdialysis in the neostriatum of the halothane-anesthetized male rats was used to study the effect of neurotensin on the release of dopamine and its metabolites in the absence or presence of systemic apomorphine treatment. Perfusate levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were assayed by high-performance liquid chromatography in combination with electrochemical detection. Perfusion with neurotensin (1000 nM but not 10 nM) increased the dialysate levels of dopamine without affecting those of DOPAC and HVA. Systemic treatment with apomorphine (0.05 and 0.5 mg/kg, s.c.) reduced the dialysate levels of dopamine, DOPAC and HVA in a dose-related way. Neurotensin (10 nM but not 1 nM) counteracted the inhibitory effect of apomorphine on dialysate levels of dopamine without affecting those of DOPAC and HVA. The results indicate a facilitatory effect of neurotensin on dopamine release in rat neostriatum. It is suggested that activation of neurotensin receptors may cause a reduction in the affinity of dopamine autoreceptors, since the low dose of neurotensin is able to counteract the inhibitory effect of apomorphine on dopamine release.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Acute treatment with clozapine blocks D1 dopamine receptor binding in discrete brain areas of the male rat.

The ability of acute treatment with clozapine in vivo to block D1 receptors in the rat telencephalon and midbrain was investigated using the irreversible inactivation of [125I]SCH 23982 binding sites by N-ethoxy-carbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ; 6 mg/kg, i.p., 24 h). As analyzed by quantitative autoradiography, clozapine (40 mg/kg, i.p., 15 min before EEDQ administration) was found to produce a partial protection of central D1 receptors in all brain areas investigated, including cerebrocortical regions. These data could perhaps explain the failure of clozapine to induce tardive dyskinesia upon chronic treatment.

Animals↗
PubMed1989

Transient forebrain ischemia produces multiple deficits in dopamine D1 transmission in the lateral neostriatum of the rat.

Striatal dopamine D1 transmission was studied in rats 7 days after transient (30 min) forebrain ischemia using the 4-vessel occlusion model. The striatal distribution of dopamine D1 ([3H]SCH 23390 binding sites) and D2 ([3H]sulpiride binding sites) receptors as well as the distribution of adenylate cyclase ( [3H]forskolin binding sites) and of the intracytoplasmic dopamine and cAMP-regulated phosphoprotein DARPP-32 related to D1 transmission were analyzed. While the distribution of D2 receptors was unaffected 7 days after the ischemic insult, all the other markers showed a patchy disappearance in the dorsolateral part of the neostriatum. These findings underline the existence of selective multiple deficits in D1 transmission after transient forebrain ischemia in rat striatum.

Animals↗
PubMed1989

Chronic nicotine treatment eliminates asymmetry in striatal glucose utilization following unilateral transection of the mesostriatal dopamine pathway in rats.

Partial hemitransection was performed through a knife lesion at the meso-diencephalic level in rats to sever the mesostriatal dopamine system. During the subsequent 2 weeks the animals received 0.125 mg/kg/h of nicotine continuously via an osmotic minipump implanted s.c. To achieve prompt high nicotine levels, 4 i.p. injections of 0.5 mg/kg nicotine were, in addition, given during the first 2 h following the lesion. The total treatment corresponded to a mean plasma level of 50 ng/ml nicotine, measured at the end of the experiment. Control animals received corresponding volumes of 0.9% saline. Quantitative autoradiographic analysis of the glucose utilization in the caudate nucleus using Sokoloff's [14C]2-deoxyglucose method demonstrated a 16% side-to-side difference in the lesioned control animals, whereas the asymmetry was counteracted by the nicotine treatment. Although there was an overall tendency to a lower rate of glucose utilization (by 6%) in the nicotine-treated animals compared to the controls receiving saline only, the difference was not statistically significant. The eliminated asymmetry probably reflects an increased survival of the dopamine neurons and/or of striatal nerve cells on the lesioned side due to protective effects of nicotine resulting from desensitization of nicotinic-type cholinergic receptors following continuous administration of the drug.

Animals↗
PubMed1989

Pertussis toxin treatment counteracts the cardiovascular effects of neuropeptide Y and clonidine in the awake unrestrained rat.

The role of G-proteins in the mediation of the cardiovascular effects of neuropeptide Y and the alpha 2-adrenoceptor agonist clonidine was investigated by injections of pertussis toxin (10 micrograms/30 microliters, i.v.t., 24 h) in the awake unrestrained male rat. Treatment with pertussis toxin was found to inhibit the hypotensive and bradycardic actions of neuropeptide Y (1250 pmol) and the hypotensive actions of clonidine (1875 pmol). Control experiments showed that treatment with pertussis toxin caused an approximately 50% reduction in the back-ADP-ribosylation of GTP-binding proteins. These results suggest that G-proteins mediate the central cardiovascular actions of neuropeptide Y and clonidine.

Animals↗
PubMed1989

Evidence for the existence of a population of arcuate neurons costoring choline acetyltransferase and tyrosine hydroxylase immunoreactivities in the male rat.

By combined immunoperoxidase and immunofluorescence histochemistry we have analyzed the distribution of choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH) immunoreactive (IR) perikarya within the same sections of the mediobasal hypothalamus of the male rat. Evidence was obtained for the existence of perikarya costoring TH and ChAT immunoreactivities in both the dorsomedial and ventrolateral part of the arcuate nucleus and in the adjacent periarcuate nucleus at all rostrocaudal levels. The results strongly implicate interactions between dopamine and acetylcholine as well as acetylcholine and growth hormone releasing factor in dorsomedially and ventrolaterally located TH/ChAT costoring tuberoinfundibular neurons, respectively.

Animals↗
PubMed1989

Coexistence of glucocorticoid receptor-like immunoreactivity with neuropeptides in the hypothalamic paraventricular nucleus.

The paraventricular nucleus (PVN) of male albino rats was analyzed for the presence of glucocorticoid receptor-like immunoreactivity (GR-LI) in neuropeptide containing neurons. Using immunohistochemistry, coronal sections trough the entire PVN were double-stained with a mouse monoclonal antibody against GR and one of the following antisera: rabbit antiserum to corticotropin releasing factor (CRF), neurotensin (NT), enkephalin (ENK), cholecystokinin (CCK), thyrotropin releasing hormone (TRH), galanin (GAL), peptide histidine isoleucine (PHI), vasoactive intestinal polypeptide (VIP), somatostatin (SOM) or tyrosine hydroxylase (TH). For comparison the occurrence of GR-LI in NT-, SOM-, NPY- or TH-positive neurons of the arcuate nucleus was also studied. Our results indicate that GR-LI is present in the parvocellular part of the PVN but not in its magnocellular portion. Virtually every parvocellular neuron in the PVN containing one of the above mentioned peptides was also positive for GR, with the exception of SOM neurons, of which only about two thirds showed detectable levels of GR-LI. All TH-positive, presumably dopamine neurons in the PVN were GR-positive. In the arcuate nucleus all TH- and NPY-positive neurons as well as a large proportion of the SOM- and NT-immunoreactive neurons contained GR-LI. The results indicate that in the PVN, in addition to the CRF neurons, certain peptidergic neurons in the parvocellular part of the PVN, without any established role in the control of ACTH synthesis and release, may also be under glucocorticoid control. This seems to be the case also for most arcuate neurons.

Animals↗
PubMed1989

Effects of withdrawal from chronic exposure to cigarette smoke on hypothalamic and preoptic catecholamine nerve terminal systems and on the secretion of pituitary hormones in the male rat.

A 48 h but not a 72 h or 7 day withdrawal from chronic exposure to cigarette smoke was associated with increased noradrenaline levels (quantitative histofluorimetry) in the subependymal layer (SEL) of the median eminence, the anterior periventricular hypothalamic region (PV I) and the parvocellular part of the hypothalamic nucleus (PA FP) and an increased noradrenaline utilization (tyrosine hydroxylase inhibition by alpha MT) in the SEL and the PV I. Following a 48 h or 72 h but not a 7 day withdrawal from chronic exposure to cigarette smoke an increased catecholamine utilization was found in the medial palisade zone (MPZ) of the median eminence. Reduced serum prolactin, FSH and corticosterone levels were found following a 48 h withdrawal from chronic exposure to cigarette smoke. Following a 72 h withdrawal from chronic exposure to cigarette smoke a reduced concentration of serum prolactin was noted. Chronic exposure to cigarette smoke reduced serum TSH levels and lead to a tolerance development with regard to noradrenaline levels and utilization within the preoptic region with the exception of the periventricular preoptic region. The finding of special interest in the present study is the demonstration of a highly significant lowering of corticosterone serum levels despite maintained blood levels of ACTH as seen 48 h following withdrawal. It is suggested that this type of endocrine change may lead to changes in fear-motivated behaviour and contribute to behavioural withdrawal reactions. The maintained reductions of serum prolactin levels found after 48 h and 72 h of withdrawal from cigarette smoke exposure (cf. Andersson et al. 1985a) is discussed in terms of an increased catecholamine utilization in the medial palisade zone of the median eminance. This activation is suggested to be caused by the development of a prolactin receptor supersensitivity within the medium eminence. The present evidence indicates withdrawal effects mainly in the noradrenaline nerve terminals of the subependymal layer of the median eminence, the anterior periventricular hypothalamic region and the parvocellular part of the paraventricular hypothalamic nucleus which inter alia are involved in regulation of ACTH secretion (cf. Andersson et al. 1985a).

Animals↗
PubMed1989

Neuropeptide Y increases the inhibitory effects of clonidine on potassium evoked 3H-noradrenaline but not 3H-5-hydroxytryptamine release from synaptosomes of the hypothalamus and the frontoparietal cortex of the male Sprague-Dawley rat.

The release of 3H-noradrenaline (3H-NA) and of 3H-5-hydroxytryptamine (3H-5-HT) evoked by high-K+ (15 mM) was studied in synaptosomes isolated from the hypothalamus and the frontoparietal cortex of the male Sprague-Dawley rat using a superfusion apparatus. Based on concentration-response curves obtained by analyzing the full-time course of the inhibitory effects of clonidine on 3H-NA and on 3H-5-HT release neuropeptide Y (NPY) (1 nM) was shown to significantly increase the ability of clonidine to inhibit 3H-NA release in synaptosomes isolated from the hypothalamus and from the frontoparietal cortex. NPY (1 nM) alone had no effect on K+-evoked 3H-NA release from these regions. In contrast, NPY (1 nM) did not modulate the inhibitory effects of clonidine on 3H-5-HT release in the above mentioned regions. These results indicate that NPY can increase the sensitivity of the alpha 2-autoreceptors belonging to hypothalamic NA and/or to adrenaline nerve terminals and to cortical NA nerve terminals, while the alpha 2-heteroreceptors inhibiting 3H-HT release in the same brain regions appear not to be regulated by high affinity NPY receptors. Thus, alpha 2-autoreceptors and alpha 2-heteroreceptors appear to be differentially controlled by high affinity NPY receptors at least with regard to regulation of 3H-NA and 3H-5-HT release, respectively.

Animals↗
PubMed1989

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)

Animals↗
PubMed1989

Reduced inhibitory effects of clonidine and neuropeptide Y on 3H-noradrenaline release from synaptosomes of the medulla oblongata of the spontaneously hypertensive rat.

The release of 3H-noradrenaline (3H-NA) evoked by high-K+ (15 mM) was studied in synaptosomes isolated from the medulla oblongata of the normotensive Wistar-Kyoto and spontaneously hypertensive male rat (14 weeks old) using a superfusion apparatus. Based on concentration-response curves clonidine was shown to have a reduced ability to inhibit 3H-NA release in synaptosomes isolated from the spontaneously hypertensive rat (SHR) versus the normotensive rat. Furthermore, only a high concentration of NPY (100 nM) had the ability to enhance the inhibitory effects of clonidine on 3H-NA release in synaptosomes isolated from the medulla oblongata of the SH male rat, while 1 nM of NPY was effective in synaptosomes isolated from the medulla oblongata of the normotensive Wistar-Kyoto rat. These results may indicate a reduced presynaptic alpha 2-adrenoceptor and NPY receptor function to inhibit 3H-NA release from NA and/or adrenaline (A) nerve terminals in the medulla oblongata of the adult 14 weeks old SHR.

Animals↗
PubMed1989

Reciprocal interactions between alpha 2-adrenoceptor agonist and neuropeptide Y binding sites in the nucleus tractus solitarius of the rat. A biochemic and autoradiographic analysis.

Interactions between a alpha 2-adrenoceptor agonist and neuropeptide Y (NPY) binding sites have been studied in the rat medulla oblongata (MO) using biochemical binding techniques as well as quantitative autoradiography. Tritiated para-amino clonidine (3H-PAC; alpha 2-adrenoceptor agonist), idazoxan (3H-IDA; alpha 2-adrenoceptor antagonist) and iodinated neuropeptide Y (125I-NPY) were used as radioligands. (1) Neuropeptide Y (NPY; 10(-8) M) but not bovine pancreatic polypeptide (BPP) nor peptide YY (PYY 10 nM) increased the KD value of 3H-PAC binding sites. However, intraventricular administration of a high dose of NPY (1.25 nmol) did not change the 3H-PAC binding characteristics in MO membrane preparations of these animals. (2) GTP 10(-4) lowered the affinity of 3H-PAC binding. NPY (10 nM) had no additional effect, nor did NPY influence the GTP induced shift in potency of clonidine to displace 3H-IDA from its binding sites. (3) In the autoradiographical experiments NPY (10 nM) significantly reduced 3H-PAC binding (2 nM) in the nucleus tractus solitarius (NTS) area by 35%. (4) When clonidine, either given centrally in vivo (3.75 nmol) or in vitro (10 nM) the binding of 125I-NPY was reduced (34 and 24%, respectively) in the NTS. When the monoamine receptors were irreversibly blocked in vivo by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ, 10 micrograms i.c. 24 h) 125I-NPY (0.5 nM) binding was increased by 137% in the NTS. This effect of EEDQ was prevented by pretreatment with the alpha 2-adrenoceptor antagonist idazoxan. These results provide support for a direct intramembrane interaction between the alpha 2-receptor and the NPY receptor within the NTS and may be of importance in central cardiovascular regulation.

Animals↗
PubMed1989

Persistent effects of neonatal toluene exposure on regional brain catecholamine levels and turnover in the adult male rat.

Effects of neonatal toluene exposure (80 ppm, day 1-7, 6 h/day) have been studied on regional brain catecholamine levels and utilization, and on serum levels of hypophyseal and adrenocortical hormones in the adult male rat. Catecholamine levels were measured by quantitative histofluorimetry in the forebrain and hypothalamus and by high pressure liquid chromatography with electrochemical detection in the substantia nigra. Catecholamine utilization was evaluated from the decrease in catecholamines seen after tyrosine hydroxylase inhibition using alpha-methyl-p-tyrosine methyl ester hydrochloride (alpha MT, 250 mg/kg, i.p., 2 h). Serum levels of thyroid stimulating hormone, corticosterone, aldosterone, prolactin and luteinizing hormone were measured by radioimmunoassays. Neonatal toluene exposure produced a reduction of dopamine levels and utilization selectively in the olfactory tubercle and substantia nigra of the adult rat. Furthermore, neonatal toluene exposure produced a significant reduction in the noradrenaline levels and utilization in the substantia nigra and an increase of noradrenaline utilization selectively in the subependymal layer of the median eminence and of the magnocellular part of the paraventricular hypothalamic nucleus. The serum hormone levels were not significantly influenced by neonatal toluene exposure as evaluated in adulthood. However, the alpha MT induced increase in serum prolactin levels was reduced following neonatal exposure to toluene. Neonatal toluene treatment was also found to alter the responses of the catecholamine neurons to subacute toluene exposure in adulthood. In some of the dopamine nerve terminal systems of the forebrain and in the dopamine cell body containing area of the substantia nigra neonatal toluene exposure appears to have made the dopamine neurons insensitive to adult subacute toluene exposure. In the hypothalamic noradrenaline nerve terminal systems, there were even reversed responses to subacute toluene exposure. The present results indicate that neonatal toluene exposure in doses at the threshold limit value produces persistent changes in dopamine and noradrenaline neurons of the forebrain, hypothalamus and substantia nigra in the presence of a relatively intact neuroendocrine system. In addition, neonatal toluene exposure appears to diminish or even counteract the responses to subacute toluene treatment in adulthood.

Administration, Inhalation↗
PubMed1989

Neuroendocrine actions of nicotine and of exposure to cigarette smoke: medical implications.

Over many years a large number of studies have demonstrated that nicotine and exposure to cigarette smoke produce marked neuroendocrine changes in animals and in man. The initial effects of nicotine are characterized by a marked hypersecretion of ACTH, vasopressin, beta-endorphin, prolactin and LH. Many of these very acute stimulatory effects of nicotine rapidly disappear, probably due to a desensitization of the central nicotinic cholinergic receptors involved. Instead, upon acute intermittent treatment with nicotine or exposure to cigarette smoke, an inhibition of prolactin, LH and TSH secretion occurs, which is associated with maintained hypersecretion of corticosterone. These effects are probably mediated via activation of central cholinergic receptors of the ganglionic type. Evidence indicates that the inhibitory effects of nicotine on LH and prolactin secretion are produced via an activation by these nicotinic receptors of the tubero-infundibular dopamine neurons, releasing dopamine as a prolactin inhibitory factor. Dopamine inhibits LHRH release via an axonic interaction involving D1-like dopamine receptors in the median eminence. It therefore seems possible that the reduced fertility found in heavy smokers may be counteracted by D1 receptor antagonists. The symptoms associated with glucocorticoid hypersecretion induced by nicotine is discussed considering not only the peripheral side effects but also permanent deficits in hippocampal glucocorticoid receptors and loss of hippocampal neurons. In view of the important influence of hormones on immune functions, it seems likely that smoking will cause disturbances in immune responsiveness. Finally, the nicotine-induced alterations of neuroendocrine function, especially in the pituitary-adrenal axis and in vasopressin release, may also lead to behavioural consequences in smokers, especially in the withdrawal phase.

Animals↗
PubMed1989

Protective effects of chronic nicotine treatment on lesioned nigrostriatal dopamine neurons in the male rat.

The present results demonstrate that chronic nicotine treatment can in part protect against mechanically-induced and neurotoxin-induced degeneration of nigrostriatal DA neurons. These results indicate that in sufficient doses chronic treatment with nicotine may be considered in the pharmacological treatment of Parkinson's disease. It remains to be demonstrated whether these protective actions can be extended to include also other injured neurons such as the cholinergic neurons, known to be severely affected in Alzheimer's disease.

Animals↗
PubMed1989

Studies of protective actions of nicotine on neuronal and vascular functions in the brain of rats: comparison between sympathetic noradrenergic and mesostriatal dopaminergic fiber systems, and the effect of a dopamine agonist.

Neuroprotective and possible trophic actions of nicotine were studied in two types of experimental models: (1) one in which the meso-striatal dopamine system was subjected to partial hemitransection, and regional glucose utilization (using 2-[3H]deoxyglucose) and blood flow (using [14C]iodoantipyrine) were measured by computer-assisted quantitative autoradiography based on a double-isotope technique; and (2) another where the sympathetic cranial nervous system supplying the brain vasculature was subjected to decentralization, axotomy, and partial or complete ganglionectomy, and the neuronal survival and fiber regeneration were elucidated by fluorescence histochemistry of noradrenaline, tyrosine hydroxylase, and neuropeptide Y. Continuous nicotine infusion for 4 weeks failed to significantly affect the neuronal response to the surgical interference of the sympathetic noradrenergic system. The same nicotine treatment for 2 weeks significantly improved glucose utilization and blood flow in caudate-putamen on the side in which the meso-striatal dopamine system had been transected, thus eliminating the 16% side-to-side asymmetry in the metabolism caused by the axotomy. The dopamine agonist, EMD 23,448, was without significant effect on this asymmetry. The hemitransection produced marked reduction in metabolism and flow also in the ventro-lateral thalamus. In substantia nigra, glucose utilization was markedly elevated--perhaps as a consequence of a regenerative increase in protein synthesis--opposite to a considerable reduction in nigral blood flow. Little or no effect of the hemitransection was seen in hippocampus or nucleus accumbens. In neither of these four regions did nicotine (or EMD 23,448) have any overt influence on glucose metabolism or blood flow. It is concluded that nicotine, mainly through its protective action on the meso-striatal dopaminergic system, is able to improve striatal glucose utilization and associated blood flow, probably reflecting a tendency to amelioration of neurotransmission function of surviving terminals belonging to the nigro-striatal dopamine neurons.

Animals↗
PubMed1989

Regional differences in glucocorticoid receptor immunoreactivity among neuropeptide Y immunoreactive neurons of the rat brain.

By means of two-colour immunocytochemistry using a mouse monoclonal antibody directed against the rat liver glucocorticoid receptor (GR) and a rabbit polyclonal neuropeptide Y (NPY) antiserum combined with the biotin-avidin immunoperoxidase and a double immunofluorescence procedure, it has been possible to demonstrate nuclear GR immunoreactivity (IR) in neurons showing cytoplasmatic NPY IR in rat brain. The majority of NPY immunoreactive perikarya of the medial parvocellular part of the arcuate nucleus, locus coeruleus and the rostral and caudal part of the ventrolateral medulla oblongata contained strong nuclear GR IR. Many of the NPY immunoreactive neurons present in the subnuclei of the nucleus tractus solitarius also contained nuclear GR IR, while most of the NPY immunoreactive perikarya of the cerebral cortex and all of the neostriatum appeared to lack GR IR. These results indicate that NPY immunoreactive neurons in the upper and lower brain stem, but not in the cerebral cortex and in the neostriatum may be directly involved in mediating central effects of glucocorticoids.

Animals↗