Biomedical subjects

E Brodin

Publications and source records attributed to E Brodin.

At least 37 records · Page 2Linked to original sources

PubMed1995

Effects of acute systemic treatment with the 5 HT-uptake blocker alaproclate on tissue levels and release of substance P in rat periaqueductal grey.

The effects of acute systemic treatment with alaproclate, a serotonin uptake blocker on regional brain tissue levels of substance P, neurokinin A and cholecystokinin were studied in the rat. The peptide levels of all three peptides were increased (23-35%) in the rat periaqueductal grey 60 min after treatment with alaproclate (20 mumol/kg peroral, p.o.), compared to controls. In the cingulate cortex, the tissue levels of substance P and cholecystokinin were increased (19-32%) after subcutaneous (s.c.) treatment with alaproclate, compared to controls. Higher tissue levels of all three peptides (20-38%) in the periaqueductal grey, and lower levels of substance P and cholecystokinin in the cingulate cortex were found following saline s.c. compared to saline p.o., probably due to different degrees of stress. In microdialysis experiments, a s.c. injection of either saline (2 ml/kg), alaproclate (20 mumol/kg) or morphine (3 mg/kg) was found to slowly increase the substance P release in the periaqueductal grey. Experiments with the selective 5-HT neurotoxin, 5,7-dihydroxytryptamine indicated no neuronal co-existence of substance P and serotonin in the periaqueductal grey and cingulate cortex. In conclusion, acute treatment with the serotonin uptake blocker alaproclate increases both the tissue level and the release of substance P in the periaqueductal grey.

5,7-Dihydroxytryptamine↗

PubMed1995

Spatiotemporal selective effects on brain-derived neurotrophic factor and trkB messenger RNA in rat hippocampus by electroconvulsive shock.

Electroconvulsive therapy is used in the treatment of affective disorders and schizophrenia and experimental electroconvulsive shock may serve as an animal model for this treatment. The aim of this study was to investigate a possible role for neurotrophins in the mechanism of action of experimental electroconvulsive shock and thus in clinical electroconvulsive therapy. The effect of electroconvulsive shock on levels of messenger RNAs encoding the neurotrophin brain-derived neurotrophic factor and the receptor trkB in rat hippocampus was determined by in situ hybridization with RNA probes 1, 3, 9 and 27 h following the shock. Brain-derived neurotrophic factor messenger RNA levels were increased at 1, 3 and 9 h following the shock and normalized after 27 h. Granule cells of the dentate gyrus showed a more rapid response as compared to hilar cells and pyramidal cells of CA1. Total trkB messenger RNA levels, including the transcripts for both the truncated and full length trkB receptor protein (gp95trkB and gp145trkB, respectively), showed a pattern of increase very similar to that of the brain-derived neurotrophic factor messenger RNA. However, using a probe selective for the full length (gp145trkB) trkB messenger RNA, we determined a delayed pattern of activation with significant increase only at 3 and 9 h after the shock. In hippocampus total trkB messenger RNA was found to consist of approximately one-quarter of mRNA encoding gp145trkB and three-quarters encoding gp95trkB as revealed by RNAase protection. While brain-derived neurotrophic factor and the truncated trkB messenger RNAs appear to increase with a similar pattern, suggesting a similar mechanism of activation by electroconvulsive shock, full length receptor trkB messenger RNA appears to increase with a delayed pattern suggesting a separate mechanism of activation. Electroconvulsive shock-induced seizures seem to include activation of a brain neurotrophin known to be important for neuronal plasticity.

Animals↗

PubMed1994

Clomipramine and clonazepam increase cholecystokinin levels in rat ventral tegmental area and limbic regions.

Recent reports suggest that a cholecystokinin (CCK)-related dysfunction may be a target by which drugs can modulate anxiety and panic disorders. In the present study, effects of subchronic (14 days) treatment with the monoamine uptake inhibitors nortriptyline (30 mumol/kg per day), amitriptyline (29 mumol/kg per day), clomipramine (32 mumol/kg per day) and alaproclate (39 mumol/kg per day), as well as with the benzodiazepine clonazepam (0.25 mumol/kg per day), on rat brain levels of CCK- and substance P-like immunoreactivity, were compared. The drugs were administered by continuous s.c. infusion using implanted osmotic pumps. The plasma concentrations of the monoamine uptake inhibitors were similar after 1 and 2 weeks of treatment, indicating that steady-state plasma levels had been reached during the first week. Treatment with clomipramine or clonazepam increased the CCK-like immunoreactivity level in the ventral tegmental area (by 64.4 +/- 28.8% and 105.1 +/- 28.8%, respectively) and in the cingulate cortex (by 30.3 +/- 10.1% and 36.0 +/- 11.8%, respectively) (P < 0.05 or P < 0.01). Clomipramine also significantly increased the CCK-like immunoreactivity level in the periaqueductal grey by 85.1 +/- 29.7%. Neither nortriptyline nor amitriptyline or alaproclate produced any significant alterations in the CCK- or substance P-like immunoreactivity levels in the areas examined. The present results may suggest that an altered utilization of CCK in limbic circuits could be of importance for the well documented clinical effect of clomipramine and clonazepam in panic disorders.

Amitriptyline↗

PubMed1994

Multiple molecular forms of tachykinins in rat spinal cord: a study comparing different extraction methods.

Various procedures for extraction at acid, neutral and alkaline pH were compared with regard to the yield of different tachykinins and tachykinin-like substances from rat spinal cord. Reverse phase high performance liquid chromatography (RP-HPLC) and radioimmunoassay with various C-terminally directed tachykinin antisera and a newly developed N-terminally directed substance P (SP)-antiserum (SPN 1) were used. Antiserum SPN 1 fully reacts with SP-analogues modified at the C-terminal end (SP free acid and SP-Gly-Lys) and also (77%) with SP(1-9) but not with C-terminal SP-fragments lacking 2 or more N-terminal amino acids. The highest levels of SP-like immunoreactivity (LI) and neurokinin A (NKA)-LI were measured after combined water and acetic acid extraction procedures. Also when measuring cholecystokinin-like immunoreactivity the highest level was obtained following this extraction procedure. RP-HPLC revealed a major component of SP-LI at the position of synthetic SP irrespectively of the extraction method and if the C- or N-terminally directed antiserum was used. Neutral water extracts contained a late eluting component detected with the C-terminally, but not with the N-terminally, directed antiserum. Acid and alkaline extracts, in contrast, contained components which could be detected with the N-terminally, but not with the C-terminally, directed SP-antiserum. Immunoreactive components eluting at the position of NKA and NKB were found in all types of extracts with NKA-, kassinin- and eledoisin-antisera. The NKB- and neuropeptide K (NPK)-components were more prominent in acid than in neutral and alkaline extracts. In conclusion, the present results indicate that rat spinal cord may contain molecular forms of tachykinin-like immunoreactivity in addition to those previously described and illustrate the importance of the choice of extraction method in immunochemical studies. Combined extraction in water and acetic acid appears to be a suitable method when the content of peptides with different chemical properties are to be measured in a tissue sample.

Animals↗

PubMed1994

Quantitation of N-terminally extended tachykinins in cerebrospinal fluid from healthy subjects.

N-terminally extended substance P (SP) and neuropeptide K (NPK), an N-terminally extended form of neurokinin A (NKA), were determined in cerebrospinal fluid (CSF) from healthy human subjects by combined high performance liquid chromatography and radioimmunoassay. The concentrations of the peptides were similar in fresh CSF and in CSF which had been kept frozen for up to 5 months. SP and NKA were not present in measurable amounts in neither fresh CSF nor in CSF that had been frozen. On the other hand, when synthetic SP and NKA were added to approx. 2 pM concentration to fresh CSF samples, both peptides were recovered to 85 and 98%, respectively. There were no significant concentration gradients of the peptides in the first 18 ml (three consecutive 6 ml fractions) of CSF (n = 10). In contrast, we confirmed previous findings, that there are gradients of the amine metabolites 5-HIAA (P < 0.01) and HVA (P < 0.001) (n = 5). The concentrations of extended SP (expressed in SP equivalents) and NPK in the first 6 ml of CSF were 1.5 +/- 0.7 pM and 14.2 +/- 6.4 pM (mean +/- S.D., n = 10), respectively. The present results thus show that the levels of N-terminally extended SP and NKA are stable in frozen CSF samples for up to 5 months. The virtual lack of SP and NKA in CSF does not seem to be due to losses during sample preparation or storage.

Adult↗

PubMed1994

Effects of sequential removal of rats from a group cage, and of individual housing of rats, on substance P, cholecystokinin and somatostatin levels in the periaqueductal grey and limbic regions.

The effect of specific stressful stimuli on neuropeptide levels was studied in rat brain regions known to be involved in the mediation of stress responses and anxiety. Rats were sequentially removed, one by one with 20-min intervals from group cages and immediately decapitated. A selective increase of the somatostatin level was observed in the amygdala in the rats taken for sacrifice second last and last, compared to the rats taken earlier from the respective group cage (increases by 40 to 69%, p < 0.05 or p < 0.01). Isolation of rats in single cages for 24 h or 1 week before sacrifice, increased the substance P level in the dorsal periaqueductal grey by 26 and 27% (p < 0.05 in both cases), respectively, compared to group housed rats. In group housed rats treated with diazepam (5 mg/kg, s.c.) 140 min before sacrifice, the level of substance P in the rostral hippocampus and dorsal periaqueductal grey was reduced by 40% (p < 0.001) and 28% (p < 0.05), respectively, compared to saline treated controls. In conclusion, handling, as well as a single dose of the anxiolytic drug diazepam, appears to induce rapid, selective and region-specific changes of regional brain peptide levels in the rat. The effects of handling are likely to be related to the acute stress response and are probably not secondary to increased plasma glucocorticoid levels.

Amygdala↗

PubMed1994

Weight bearing as an objective measure of arthritic pain in the rat.

This study compares two methods for evaluating pain-related behavior in an animal model with carrageenan-induced monoarthritis. Rats injected with lambda-carrageenan into the right tibio-tarsal joint were videofilmed at various times after injection and later scored regarding their stance. Immediately after each videorecording session the animals were tested in a box constructed to register the weight load exerted by the hindpaws by means of force plates inserted in the floor. Following carrageenan injection (300 micrograms in 50 microL) the load on the injected paw fell from a control value of 39.3% +/- 0.4% of the body weight (mean +/- SEM, n = 6) to a minimum of 5.1% +/- 1.8% at 6 hr and then slowly increased to approach control levels at 72 hr. The weight load on the contralateral paw increased from a control value of 38.9% +/- 0.6% to 52.4% +/- 1.4% at 6 hr, whereafter it gradually decreased. The video-based stance scores also showed a maximal impairment at 4-6 hr, with a gradual return towards control values at 72 hr. However, the results based on the force plate measurements were less variable and more graded. Morphine inhibited the carrageenan-induced effect in a dose-dependent manner in both paradigms. In conclusion, the present results indicate that measurement of weight bearing as described in the present paper is a practical, useful, and objective method to assess the degree of arthritic pain in the rat.

Animals↗

PubMed1994

On the origin of striatal cholecystokinin release: studies with in vivo microdialysis.

In the present study, extracellular levels of the neuropeptide cholecystokinin (CCK), of the monoamine dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and of the excitatory amino acids glutamate and aspartate were simultaneously monitored by microdialysis in the neostriatum of halothane-anesthetized rats under basal and K(+)-depolarizing conditions. Extracellular CCK and dopamine levels, but not glutamate and aspartate levels, were decreased by perfusion with a Ca(2+)-free medium, under both basal and K(+)-depolarizing conditions. HPLC revealed that the majority of the CCK-like immunoreactivity in the perfusates coeluted with CCK octapeptide. Striatal extracellular CCK levels were decreased by decortication plus callosotomy, with a parallel decrease in glutamate levels. Striatal extracellular levels of dopamine, DOPAC, and HVA were significantly decreased in animals treated previously with a unilateral 6-hydroxydopamine injection into the medial forebrain bundle. In these animals, however, the effect of decortication plus callosotomy on CCK and glutamate levels was not further augmented. Thus, this study supports the hypothesis of a neuronal origin of extracellular CCK and dopamine monitored with microdialysis in the striatum of the rat, and also supports the idea of a partly contralateral origin of corticostriatal CCK and glutamate inputs.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Gamma-aminobutyric acid is released in the dorsal horn by electrical spinal cord stimulation: an in vivo microdialysis study in the rat.

The mechanism underlying the beneficial effect of electrical stimulation of the posterior surface of the spinal cord in chronic pain states are unknown. The prolonged pain relief following a short stimulation period is believed to imply the activation of long-lasting neurochemical processes, mainly in the spinal cord, but possibly also involving other parts of the central nervous system. Previous studies have demonstrated that substance P and serotonin are released in the cat dorsal horn during spinal cord stimulation (SCS) with electrical parameters similar to those used in the clinic. However, gamma-aminobutyric acid (GABA) has also been hypothesized to play a role in the effect of SCS, but there have been no studies of the possible effects of SCS on GABA release. The authors applied SCS to anesthetized rats and monitored the extracellular concentration of GABA in the lumbar dorsal horns by microdialysis and a sensitive reverse-phase high-performance liquid chromatography technique. After 30 minutes of SCS, the GABA level increased significantly (by almost 270%) in comparison with the basal level recorded before stimulation, from 3.6 +/- 1.0 nmol/L to 13.1 +/- 2.2 nmol/L (mean +/- the standard error of the mean; P < 0.05). The peak release was delayed and appeared in the 30-minute fraction collected after stimulation. Also, perfusion of the dialysis probes with potassium (100 mmol/L) induced an increase of the GABA level. In control experiments without electrical stimulation, slowly decreasing GABA levels were observed throughout the experiments. The present results may suggest an involvement of GABA in the mechanism of SCS-induced pain relief.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

N-terminally extended tachykinins in human cerebrospinal fluid.

With HPLC-RIA methods we were unable to demonstrate SP and NKA in measurable amounts in human CSF. Instead N-terminally extended forms of these peptides were found to be present and could be quantitated. The finding that these forms of tachykinins can be released from nervous tissue might suggest that their levels in CSF can be used as markers of the activity in central SP and NKA neurons.

Animals↗

PubMed1993

An animal model for the study of brain transmittor release in response to spinal cord stimulation in the awake, freely moving rat: preliminary results from the periaqueductal grey matter.

Electrical spinal cord stimulation (SCS) is an important method in the treatment of certain chronic pain syndromes which are difficult to manage with conventional techniques. The indications for this procedure have gradually narrowed to neuropathic pain states, especially those of peripheral origin, ischaemic pain due to peripheral vascular disease, and treatment-resistant angina pectoris. In spite of the clinical use of this method for more than 20 years, the mechanisms underlying the pain alleviating effect remain largely unknown. For the effect on ischaemic pain, recent animal research indicates a mediation via autonomic pathways. Concerning the effect on neuropathic pain progress in knowledge has been scanty. Data from spinal microdialysis in decerebrated or anaesthetized animals indicate the possible importance of serotonin and substance P in the dorsal horn for pain inhibition by SCS. However, data from experiments on anaesthetized animals are, for several reasons, not likely to truely reflect the mechanisms active in conscious humans under treatment with SCS. To avoid the influence of anaesthesia and to approach the clinical situation, we have developed an animal model enabling simultaneous SCS and supraspinal microdialysis in awake, freely moving rats. The animal model is described and some preliminary data indicating a release of gamma-amino butyric acid (GABA) induced by SCS in the periaqueductal grey matter (PAG), are presented.

Animals↗

PubMed1993

Differential release of endogenous 5-hydroxytryptamine, substance P, and neurokinin A from rat ventral spinal cord in response to electrical stimulation.

The release of endogenous 5-hydroxytryptamine (5-HT), substance P (SP), and neurokinin A (NKA) from superfused tissue slices of rat ventral lumbar spinal cord, where SP and NKA coexist with 5-HT in terminals of descending bulbospinal neurons, was investigated. Electrical field stimulation was performed using square-wave pulses of 2-ms duration and 30 mA stimulus intensity. The following four different patterns of stimulation were used: 2 Hz continuous, 20 Hz continuous, 20 Hz intermittent, and 50 Hz intermittent. 5-HT was measured in the slice superfusates by HPLC with electrochemical detection. SP and NKA were measured by radioimmunoassay. The release of 5-HT was significantly enhanced using all stimulation paradigms and the evoked release of 5-HT per pulse was independent of the stimulation frequency. The release was found to be calcium dependent and there was no increase in the efflux of 5-hydroxyindoleacetic acid in response to stimulation. At 2 Hz (continuous), no significant increase in the release of SP was observed. Stimulation at higher frequencies yielded a significant increase in the release of SP per pulse. At 20 Hz, the release was increased by 73% (continuous) and 74% (intermittent), and at 50 Hz (intermittent) by 175% of basal efflux. The evoked release of NKA was also frequency dependent. At 2 Hz (continuous), no significant increase in the release of NKA was observed. At 20 Hz (intermittent), the evoked release per pulse was increased by 33% and at 50 Hz (intermittent) by 53% compared with the basal efflux of NKA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Extracellular somatostatin measured by microdialysis in the hippocampus of freely moving rats: evidence for neuronal release.

Intracerebral microdialysis combined with a sensitive and specific radioimmunoassay was used to monitor the neuronal release of somatostatin (somatostatin-like immunoreactivity, SLI) in the dorsal hippocampus of freely moving rats. The sensitivity of the radioimmunoassay was optimized to detect < 1 fmol/ml. The basal concentration of SLI in 20-min dialysate fractions (5 microliters/min) collected 24 h after probe implantation was stable over at least 200 min. The spontaneous efflux dropped by 54 +/- 6.4% (p < 0.05) when Ca2+ was omitted and 1 mM EGTA added to the Krebs-Ringer solution and by 65.5 +/- 3.2% (p < 0.05) in the presence of 1 microM tetrodotoxin. Depolarizing concentrations of the Na+ channel opener veratridine (6.25, 25, 100 microM) induced 11 +/- 2 (p < 0.05), 17 +/- 2 (p < 0.05), and 21 +/- 5 (p < 0.01) fold increase in SLI concentration, respectively, during the first 20 min of perfusion. The effect of 100 microM veratridine was blocked by coperfusion with 5 microM tetrodotoxin (p < 0.01) and reduced by 79% (p < 0.01) in the virtual absence of Ca2+. Neuronal depolarization by 20 min of perfusion with Krebs-Ringer solution containing 25 and 50 mM KCl and proportionally lowered Na+ increased the dialysate SLI 4.4 +/- 1 (p < 0.05) and 17 +/- 3 (p < 0.01) fold baseline, respectively. Ten micromolar ouabain, a blocker of Na+,K(+)-ATPase, increased the dialysate SLI 15-fold baseline, on average (p < 0.05), during 80 min of perfusion. The results demonstrate the suitability of brain microdialysis for monitoring the neuronal release of SLI and for studying its role in synaptic transmission.

Animals↗

PubMed1993

On the involvement of tachykinin neurons in the secretory nervous reflex elicited by cholera toxin in the small intestine.

The possible involvement of tachykinins in the nervous reflex activated by exposing the intestinal mucosa to cholera toxin was investigated in cats and rats. Three types of experiments were performed. In cats the release of tachykinins into blood was followed after placing cholera toxin in the intestinal lumen. In rat experiments a tachykinin receptor antagonist (Spantide II) was given close i.a. and its effect on cholera toxin-evoked fluid secretion was studied. Finally, in rats the effect of cholera toxin on the SP contents in the intestinal mucosa was studied. No release of tachykinins could be demonstrated. Spantide II did not change the rate of cholera toxin induced secretion. The SP content in the intestinal mucosa was not influenced by placing the toxin in the intestinal lumen. Hence, no experimental evidence was obtained for the involvement of a tachykinin neuron in the intestinal secretory nervous reflex activated by cholera toxin. Based on observations reported in the literature the involvement of an acetylcholine/tachykinin neuron in the reflex is tentatively discussed.

Animals↗

PubMed1993

Release of neurotransmitters in the CNS by spinal cord stimulation: survey of present state of knowledge and recent experimental studies.

Electric stimulation applied to the posterior surface of the spinal cord (SCS) is an established treatment in certain chronic pain syndromes resistant to conventional therapeutic procedures. Despite the clinical value of SCS, the mechanisms behind the efficacy of the method are largely unknown. Several neurotransmitters in the CNS (e.g. opioids, serotonin, noradrenaline, substance P, GABA), have been proposed to be involved in the pain-alleviating effect of SCS. However, as yet there is no evidence that these would be involved in the beneficial effects of SCS. We have studied neurotransmitter release, using microdialysis techniques, in the spinal dorsal horn and the periaqueductal grey substance (PAG) of the rat and the cat, induced by SCS applied with current parameters equivalent to those used clinically in man. Up to now dialysates have been assayed for GABA, serotonin and substance P with highly sensitive methods. Three groups of studies have been carried out: (1) dorsal horn microdialysis in rats under halothane anesthesia during acute SCS; (2) dorsal horn microdialysis in cats under barbiturate anesthesia or following decerebration, and (3) PAG microdialysis in awake, unrestrained rats with chronic SCS. In the dorsal horn studies, microdialysis probes of different sizes were implanted in the lower lumbar dorsal horns. In the PAG studies, rats had guide cannulas for microdialysis stereotactically inserted into the PAG. SCS was applied at a low thoracic level with 50 or 100 Hz; 0.2 ms and an intensity amounting to 2/3 of the motor threshold. The microdialysis probes were perfused with modified Ringer's solution. Fractions of the dialysate were collected at various intervals. GABA and serotonin were assayed by reverse-phase HPLC, while substance P was investigated using a highly sensitive radioimmunoassay. SCS induced a significant release of GABA in the dorsal horn, most marked in the fraction following the stimulation period. In the rats with PAG microdialysis, the GABA level decreased significantly following two stimulation periods, although transitional increases during SCS were noted in some animals. In the decerebrated cat, a significant release of serotonin in the dorsal horn was obtained with SCS, while the levels of the metabolite 5-HIAA were little influenced by stimulation. On the contrary, in the decerebrated preparation there was no release of substance P in the dorsal horn with SCS, although in the intact cat under barbiturate anesthesia a significant release was induced.4+ off

Animals↗

PubMed1992

Thyrotropin-releasing hormone (TRH)-like immunoreactivity in the grey monkey (Macaca fascicularis) spinal cord and medulla oblongata with special emphasis on the bulbospinal tract.

The distribution of thyrotropin-releasing hormone (TRH)-like immunoreactivity (LI) has been studied in the grey monkey (Macaca fascicularis) spinal cord and medulla oblongata by the use of indirect immunofluorescence and the peroxidase-antiperoxidase (PAP) technique. Furthermore, double-labeling experiments were performed in order to study colocalization of 5-hydroxytryptamine (5-HT)- and substance P-LI. A dense innervation of TRH-immunoreactive (IR) varicose fibers was found in the ventral horn motor nuclei, in the region surrounding the central canal, in the intermediolateral cell column, and in the dorsal horn laminae II and III. In addition, cell bodies harboring TRH-LI were found in the dorsal horn laminae II-IV. In the ventral horn, many of the large cell bodies and their proximal dendrites were totally encapsulated by TRH-IR fibers. From double-labeled sections a high degree of coexistence could be established between TRH-/5-HT-LI, TRH-/substance P-LI, and 5-HT-/substance P-LI in fibers in the motor nuclei; as a consequence, a large proportion of these fibers should harbor TRH-/5-HT-/substance P-LI. A coexistence between TRH-/5-HT-LI could also be demonstrated in the intermediolateral cell column. However, no unequivocal coexistence could be found between TRH-/substance P-LI and 5-HT-/substance P-LI in this region. In the dorsal horn, no clear coexistence could be encountered for any of the above indicated combinations. Electron microscopic analysis of material from the lumbar lateral motor nucleus demonstrated TRH-IR terminals making synapses with large cell bodies and dendrites. In addition, contacts lacking synaptic specializations could also be verified. In the medulla oblongata, with the use of the PAP technique, a large number of cell bodies containing TRH-LI were encountered in the midline raphe nuclei and in nucleus reticularis lateralis. A similar distribution pattern could be found for 5-HT-LI, but no cell bodies containing substance P-LI could be seen in these regions. Chemical analysis of specimens from cervical, thoracic, and lumbar spinal cord revealed higher concentrations of TRH- and 5-HT-LI in the ventral quadrants, whereas substance P-LI dominated in the dorsal quadrants. Thus, the concentrations of TRH-, 5-HT-, and substance P-LI was in accordance with the observed regional variation in density of IR-fibers and varicosities found in the spinal cord. We have shown that TRH-LI has a distribution in the monkey spinal cord and medulla oblongata similar to that previously demonstrated in other species.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

Amphetamine regulation of mesolimbic dopamine/cholecystokinin neurotransmission.

The effects of acute and repeated amphetamine administration on mesolimbic dopamine (DA) neurons was assessed by studying DA and cholecystokinin (CCK) release in the nucleus accumbens (Acc), as well as effects on mRNA genes regulating DA and CCK synthesis in ventral tegmental area (VTA) cells in rats. Amphetamine (1.5 mg/kg) markedly increased extracellular levels of DA in the medial Acc (assessed by in vivo microdialysis) in drug-naive animals, about twice the amount released in animals repeatedly administered the drug for the previous 7 days (twice daily). CCK overflow was found to mirror the DA responses in that the very transient elevation of CCK monitored in drug-naive animals was attenuated in those with prior amphetamine use. The attenuation of both DA and CCK overflow in the medial Acc was found to be associated with a decrease in the number of CCK mRNA-positive VTA neurons (assessed by in situ hybridization histochemistry). Although the number of cells expressing CCK mRNA were decreased, the gene expression in those positive CCK and tyrosine hydroxylase mRNA cells in the VTA was significantly increased. The CCK mRNA neurons in the VTA were positively identified as those projecting to the medial Acc by the local perfusion of Fluoro-gold retrograde tracer via microdialysis probes located in the Acc.

Amphetamine↗

PubMed1992

Cholecystokinin is released from a crossed corticostriatal pathway.

The release of striatal cholecystokinin, glutamate, aspartate and dopamine was studied in vivo with microdialysis in decorticated rats, with or without callosotomy. Unlesioned rats were also analysed. Unilateral decortication produced a unilateral decrease in K(+)-stimulated extracellular striatal glutamate and aspartate levels, without decreasing cholecystokinin or dopamine levels. However, following decortication plus callosotomy, basal and K(+)-stimulated extracellular cholecystokinin and glutamate levels were significantly decreased in the striatum ipsilateral to side of decortication. Aspartate levels were bilaterally decreased. These results give evidence for the existence of crossed corticostriatal projections containing releasable cholecystokinin and glutamate.

Animals↗