Restoration of dopamine transmission in graft reinnervated striatum. Evidence for regulation of dopamine D2 receptor function in regions lacking dopamine.
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Animals↗
Biomedical subjects
J Kehr
Publications and source records attributed to J Kehr.
Intracerebral infusion of H-dopamine and H-mannitol in the striatum of halothane-anaesthetized male rats. A dual-probe microdialysis study of long-distance diffusion.
This report characterizes an in vivo intracerebral long-distance diffusion model using dual-probe microdialysis. Two probes 1 mm apart were implanted into the striatum of control and 6-hydroxydopamine (6-OHDA)-lesioned halothane-anaesthetized male rats. Either tritiated dopamine (500 nM 3H-DA) or mannitol (1.5 microM 3H-mannitol) was infused continuously for 5 h, while samples were collected from the other probe. Samples (10 microl) were counted by liquid scintillation. For the DA-infused rats, another 10 microL was separated with high-pressure liquid chromatography (HPLC)-electrochemical detection into individual fractions containing 3,4-dihydroxy phenylacetic acid (DOPAC) and homovanillinic acid (HVA), and counted for beta-decay. The total transfer of 3H-labelled compounds described the overall effect of cellular uptake, metabolism and clearance into the microcirculation, and was compared with that of an extracellular marker, 3H-mannitol. The migration reached steady-state levels, generating an equilibrium between delivery and removal from the extracellular space. The half-time of the steady-state values, t50%, was in all cases lower in 6-OHDA-treated rats compared with control. In addition, the t50% values of 3H-mannitol were lower than those following the 3H-dopamine infusion in both control or 6-OHDA-lesioned rats. However, it was not possible to detect any unmetabolized 3H-dopamine at the 1 mm distance. In conclusion, the dual-probe microdialysis approach proved to be a valid method to study in vivo diffusion and migration in the brain, and the intracerebral spread of compounds highly depends on the nature of the compound infused.
Anesthetics, Inhalation↗
Galanin and learning.
A number of studies indicate that galanin (GAL) is a potent modulator of basal acetylcholine release in the rat forebrain e.g. in the cholinergic neurons of the septo-hippocampal projections. Thus, GAL perfused through the microdialysis probe decreased basal acetylcholine release in the ventral hippocampus, while it enhanced acetylcholine release in the dorsal hippocampus. This finding indicates that GAL may act via different mechanisms within the subsystems of the hippocampus. This hypothesis has received support from studies using the Morris swim maze, a learning task dependent on hippocampal mechanisms. GAL (3 nmol/rat) infused into the ventral hippocampus impaired spatial learning acquisition, while it tended to facilitate when injected into the dorsal hippocampus. However, the effects of GAL on acetylcholine release and on spatial learning, which are due to activation of GAL-receptors, appear to be indirectly mediated possibly via noradrenaline transmission. GAL is also a potent inhibitor of mesencephalic 5-HT neurotransmission in vivo. These findings are discussed in relation to the role of acetylcholine and serotonin in cognition.
Acetylcholine↗
Determination of norepinephrine in microdialysis samples by microbore column liquid chromatography with fluorescence detection following derivatization with benzylamine.
A microbore column liquid chromatographic method is described for the determination of norepinephrine (NE) in microdialysis samples from rat brain. The method is based on precolumn derivatization of NE with benzylamine in the presence of potassium hexacyanoferrate(III) resulting in a highly fluorescent and stable benzoxazole derivative. Typically, a 10-microl sample was mixed with 10 microl derivatization reagent containing 0.45 M Caps buffer (pH 12.0), 0.2 M benzylamine, 10 mM potassium hexacyanoferrate(III), and N,N-dimethylformamide (1:1:1:15, v/v). The derivatization was carried out at 50 degrees C for 20 min. Under these conditions only NE and epinephrine produced high fluorescence yields at excitation and emission wavelengths of 345 and 480 nm, respectively, while fluorescence of other catechols and 5-hydroxyindoles was quenched by 10-100 times. The NE derivative was separated on a reversed-phase column (100 x 1.0 mm i.d., packed with C18 silica, 5 microm) within 10 min with no late eluting peaks. The mobile phase consisted of 40 mM Britton-Robinson buffer (pH 7.5) containing 1 mM didodecyldimethylammonium bromide and acetonitrile (34%, v/v), the flow rate was 40 microl/min. The limit of detection (signal-to-noise ratio of 3) for NE was 90 amol in 10 microl sample injected. Microdialysis samples were collected in 5-min intervals from the probes implanted in the hippocampus, frontal cortex, or hypothalamus of awake rats. The basal extracellular NE levels in the respective areas were 4.7 +/- 0.9, 1.8 +/- 0.3, and 0.8 +/- 0.2 fmol/10 microl (mean +/- SE, n = 7). Perfusion with a Ringer solution containing 100 mM K+ increased hippocampal NE levels by 700%, while NE uptake inhibitors maprotiline and amitriptyline administered orally or subcutaneously increased extracellular NE in the frontal cortex by about 300%. On the other hand, reserpine (5 mg/kg) reduced cortical NE levels by 40% 3 h after the administration. This new fluorescence derivatization method provides better selectivity, sensitivity, and speed for NE determination than the electrochemical detection since no late-eluting compounds such as dopamine, serotonin, and their metabolites are detectable in the chromatograms of the microdialysis samples.
Adrenergic Uptake Inhibitors↗
Analysis of phloem protein patterns from different organs of Cucurbita maxima Duch. by matrix-assisted laser desorption/ionization time of flight mass spectroscopy combined with sodium dodecyl sulfate polyacrylamide gel electrophoresis.
Sieve tubes mediate the long-distance transport of nutrients and signals between source and sink organs of plants. To detect mobile phloem proteins that are differentially distributed in source and sink organs of Cucurbita maxima, we used both one-dimensional gel electrophoresis (SDS-PAGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Both techniques revealed that phloem protein patterns depend on the sampling site: whilst several proteins were consistently observed in all phloem samples studied others appeared to occur in a organ-specific manner. For a characterization and identification of distinct phloem polypeptides, two approaches were chosen. First, protein bands resolved by SDS-PAGE were eluted from the polyacrylamide gel and the masses of the proteins were then determined by MALDI-TOF MS. Second, proteins resolved by SDS-PAGE were subjected to proteolytic degradation and the resulting peptides were analyzed by MALDI-TOF MS: the masses of the proteolytic peptides were used for a database search. By the latter approach, three mobile phloem compounds were identified as the phloem-specific protein PP2 (D.E. Bostwick et al., 1992, The Plant Cell 4, 1539-1548) a chymotrypsin and an aspartic proteinase inhibitor. None of the other polypeptides studied corresponded to any of the protein sequences present in the database. Furthermore, MALDI-TOF MS analyses indicated that some of the mobile phloem proteins occur in a covalently modified form and that the extent of the modification depends upon the plant organ.
Amino Acid Sequence↗
Adenosine A2A and group I metabotropic glutamate receptors synergistically modulate the binding characteristics of dopamine D2 receptors in the rat striatum.
There is experimental evidence for the existence of interactions between metabotropic glutamate (mGlu), adenosine and dopamine receptors in the striatum. In membrane preparations from rat striatum the group I and II mGlu receptor agonist 1-aminocyclopentane-1S-3R-dicarboxylic acid (1S-3R-ACPD) was found to modulate the binding characteristics of D2 receptors in a similar manner as the A2A receptor agonist 2-[p-(2-carboxyethyl)phenthylamino]-5'-N-ethylcarboxamidoadenosine (CGS 21680), with a significant decrease in the affinity of the high-affinity state of D2 receptors for dopamine. The effect of 1S-3R-ACPD was mimicked by (+/-)-trans-ACPD (t-ACPD; a racemic mixture of 1S-3R-ACPD and its inactive isomer 1R-3S-ACPD) and by the selective group I mGlu receptor agonist 3,5-dihydroxyphenylglycine (DHPG) and it was counteracted by the selective group I mGlu receptor antagonist 1-aminoindan-1,5-dicarboxilic acid (AIDA), but not by the the group II and III mGlu receptor antagonist (RS)-alpha-methyl-4-tetrazolylphenylglycine (MTPG) or the adenosine receptor antagonist 8-phenyltheophylline. Furthermore, a strong synergistic effect was observed when the striatal membranes were exposed to both CGS 21680 and 1S-3R-ACPD. In agreement with the biochemical results, in unilaterally 6-OH-dopamine lesioned rats 1S-3R-ACPD counteracted the turning behaviour induced by the D2 receptor agonist quinpirole, but not by the D1 receptor agonist SKF 38393, and it synergistically potentiated the antagonistic effect of CGS 21680 on quinpirole-induced turning behaviour.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
Technical Advance: A rapid method for detection of plant gene transcripts from single epidermal, mesophyll and companion cells of intact leaves.
A protocol for the detection of gene transcripts from single plant cells in living, undamaged plant tissue is described. Samples of leaf epidermal, mesophyll and companion cells were extracted by using glass microcapillaries and directly subjected to RT-PCR without any purification steps nor time consuming construction of cDNA libraries. The procedure is not restricted to surface cells or outer cell layers. Even cells from the central region of leaves could be harvested. For identification, companion cells were labelled by expression of the green fluorescent protein under control of a companion cell specific promoter. The described method is applicable to a wide range of plants and genes with different expression levels.
Journal Article↗
Modulation of acetylcholine and serotonin transmission by galanin. Relationship to spatial and aversive learning.
This paper presents evidence that galanin is a potent in vivo modulator of basal acetylcholine release in the rat brain with qualitatively and quantitatively differential effects in the dorsal and ventral hippocampus. Galanin perfused through the microdialysis probe decreased basal acetylcholine release in the ventral hippocampus, while it enhanced acetylcholine release in the dorsal hippocampus. Galanin (3 nmol/rat) infused into the ventral hippocampus impaired spatial learning acquisition, while it tended to facilitate acquisition when injected into the dorsal hippocampus. These effects appear to be related to activation of GAL-R1 (ventral hippocampus) and GAL-R2 (dorsal hippocampus) receptors, respectively. However, the effects of galanin on acetylcholine release and on spatial learning appear not to be directly related to cholinergic mechanisms, but they may also involve interactions with noradrenaline and/or glutamate transmission. Galanin administered into the lateral ventricle failed to affect acetylcholine release, while this route of administration produced a long-lasting reduction in 5-HT release in the ventral hippocampus, indicating that galanin is a potent inhibitor of mesencephalic 5-HT neurotransmission in vivo. Subsequent studies supported this hypothesis, showing that the effects on 5-HT release in vivo are most likely mediated by a galanin receptor in the dorsal raphe. The implications of these findings are discussed in relation to the role of acetylcholine in cognitive functions in the forebrain and the role of the raphe 5-HT neurons in affective disorders.
Acetylcholine↗
Simultaneous determination of acetylcholine, choline and physostigmine in microdialysis samples from rat hippocampus by microbore liquid chromatography/electrochemistry on peroxidase redox polymer coated electrodes.
Microbore column liquid chromatography with post-column immobilized enzyme reactor (IMER) and electrochemical detection on redox polymer coated electrodes was used for detection of acetylcholine (ACh) and choline (Ch) in microdialysis samples. The sensitivity of the coated electrodes, decreased gradually by about 10%/day, with highest reduction of 30% within the first 16 h of use. A number of choline derivatives were tested as possible internal standards, of those acetylethylhomocholine (AEHCh) and butyrylcholine (BCh) were found the most suitable candidates since they both provided high enzymatic conversion in the IMER. Physostigmine produced a negative peak, possibly reflecting oxidation of eseroline--a decarbamoylated product of reversible reaction of physostigmine with immobilized acetylcholine esterase. The probes, implanted in the ventral hippocampi of awake rats were perfused at a flow-rate of 1.25 microl/min with Ringer solution containing 10 microM physostigmine or with artificial cerebrospinal fluid only. The concentrations of ACh in 10-microl samples at basal conditions were between 0.9-2.5 nM, whereas in the presence of physostigmine the ACh levels raised to 41-48 nM. Physostigmine concentration was reduced to 8.8 microM, indicating its in vivo delivery of about 12%. The coefficients of variation were reduced from 7.4% for external standard method after every sixth sample to 5.8% and 5.9% for internal standardization with AEHCh and BCh, respectively. The latter method shortened the total analysis time by about 15%, thus being especially suitable for continuous long-lasting off-line or on-line monitoring. Additionally, other endogenous cholines such as butyrylcholine or synthetic choline derivatives could be detected by the present method.
Acetylcholine↗
Determination of gamma-aminobutyric acid in microdialysis samples by microbore column liquid chromatography and fluorescence detection.
A method for the determination of gamma-aminobutyric acid (GABA) at concentrations as low as 1.5 nM in microdialysis samples is described. A high-performance liquid chromatography (HPLC) autosampler was used for precolumn derivatizations of samples with phthalaldehyde-2-mercaptoethanol reagent, as well as for automated injections of acetonitrile to wash the microbore column between injections. This permitted the use of only one isocratic pump and reduced the run-to-run analysis time to below 20 min, without any risk for late-eluting peaks. Three different microbore columns were evaluated. The optimal column was a 150 x 1 mm I.D., C18 reversed-phase silica column with a particle size of 3 microm, operated at a flow-rate of 50 microl/min. The mobile phase was 0.1 M sodium acetate buffer, pH 5.4, containing 20% acetonitrile. Under these conditions, the column exhibits a low back-pressure of about 11.1 MPa and is usable for at least 1000 injections. Good correlation was found between fluorescence and electrochemical detector responses for o-phthaldialdehyde-GABA derivatives, although the latter detector type generally required more skill and maintenance for routine use. Microdialysis samples of 10-20 microl, recovered from various rat brain nuclei, were assayed using the described method.
Animals↗
Determination of glutamate and aspartate in microdialysis samples by reversed-phase column liquid chromatography with fluorescence and electrochemical detection.
Five different systems for fast determination of aspartate and glutamate in microdialysis samples are described: (I) a high-speed HPLC using a gradient pump with a sharp elution profile, (II) a column switching technique, (III) an isocratic pump with a low-pressure switching valve for one-step gradients, (IV) microbore chromatography using injections of acetonitrile as a wash-out step, (V) on-line connection of microdialysis and HPLC/derivatization. In all cases, automated precolumn derivatization with o-phthalaldehyde-2-mercaptoethanol reagent were used. Both fluorescence and electrochemical detection techniques were evaluated in terms of reproducibility, sensitivity, interference, maintenance and troubleshooting. The electrochemical detection method required a second derivatization step with 0.2 M iodoacetamide to remove excess of a thiol moiety and regular recalibrations after each six to ten injections. Under these conditions the correlation coefficients for electrochemical vs. fluorescence detectors were 0.918 for Asp and 0.988 for Glu for 65 microdialysis samples. Coefficients of variation for six analyses between calibrations were below 3% for both detectors. The limits of detection for both amino acids were about 0.4 pmol for electrochemical detection with a thiol scavenger step, 50 fmol for fluorescence detection using conventional columns and about 20-30 fmol for the microbore system. All systems are suitable for detecting basal levels of Asp and Glu in 5-10 microl microdialysis samples from a rat brain where typical concentrations lie around 1-10 pmol or more. It is concluded that a microbore setup with one isocratic pump and an autosampler optimized for injections of washing solvent between samples is the most practical and economical. The system allows analysis of minute sample volumes down to 1-2 microl.
Animals↗
Transgenic plants changed in carbon allocation pattern display a shift in diurnal growth pattern.
Photosynthesis, partitioning of carbohydrates and growth have to be highly orchestrated to enable an efficient performance of plants. To study the diurnal relationships between carbon distribution and growth, we analysed transgenic potato plants with altered carbon allocation patterns. To modify carbohydrate supply of growing sinks, we used plants that accumulated starch as a consequence of inhibition in triose-phosphate export from chloroplasts and plants that were genetically inhibited in starch production. Carbon assimilation was analysed by gas exchange and single cell analysis of source leaves. Export was determined by microanalysis of phloem exudates and internodal growth rates were measured by displacement transducers. Gas exchange measurements showed similar assimilation rates in the wild-type and transgenic plants during the light period. Sugar analysis of phloem exudates and epidermal cells revealed a severe shift of sucrose concentrations in the individual plant lines. Moreover, epidermal cells turned out to be a potential storage site for carbohydrates in potato. Finally, we could demonstrate that changing the diurnal rhythm of carbon allocation results in a change in the diurnal growth pattern.
Animals↗
Microbore high-performance liquid chromatographic method for measuring acetylcholine in microdialysis samples: optimizing performance of platinum electrodes.
A microbore high-performance liquid chromatographic method with electrochemical detection was applied to the measurement of acetylcholine in microdialysis samples. There was an excellent linear relationship (r=0.99998) between the concentration of acetylcholine injected onto the column and the peak height (0.05-10 pmol/5 microl). During the validation of this method, we noticed that the peak height for acetylcholine decreased over time, coupled with the appearance of a brown coating on the surface of the platinum electrode. Repeated measurement of acetylcholine standards which had been stored at 4 degrees C and -20 degrees C before and after cleaning the platinum electrode with ethanol or methanol indicated that the decrease in the peak height of acetylcholine is caused by a decrease in sensitivity of the electrode itself. Results with a second microbore high-performance liquid chromatographic system confirmed these findings. On the basis of these results, we recommend that the platinum electrode is cleaned periodically with ethanol or methanol, and that quantitation is regularly calibrated with external acetylcholine.
Acetylcholine↗
Differential effects of the neuropeptide galanin on striatal acetylcholine release in anaesthetized and awake rats.
1. In the present study the mechanisms were examined by which the neuropeptide galanin modulates the extracellular concentrations of striatal acetylcholine (ACh) in enflurane anaesthetized and in freely moving male rats by use of in vivo microdialysis and high performance liquid chromatography. 2. The perfusion of galanin through the microdialysis probe (0.3 nmol microl(-1), flow rate: 2 microl min(-1)) caused a statistically significant increase in the basal striatal ACh levels in anaesthetized but a decrease in awake animals. No significant effect was revealed after a low dose (0.1 nmol microl(-1), flow rate: 2 microl min(-1)) of galanin perfusion. Both the stimulating and inhibitory effects of galanin on basal ACh release were reversible. 3. The muscarinic antagonist scopolamine (0.1 mg kg(-1), subcutaneously (s.c.)) caused a significant increase in ACh release in both anaesthetized and awake animals. 4. The combination of galanin plus scopolamine attenuated the stimulant effect on ACh release caused by scopolamine alone in awake animals. 5. The putative galanin receptor antagonist M35 at 0.3 nmol microl(-1) but not at 0.1 nmol microl(-1) caused a significant reduction (20%) in ACh release, supporting the view that M35 at higher concentrations behaves as a partial agonist at the galanin receptor. When M35 (0.1 nmol microl(-1)) was co-infused with galanin (0.3 nmol microl(-1)) the galanin-evoked decrease in ACh release was completely blocked. 6. Taken together, these results indicate that galanin affects basal ACh release via stimulation of galanin receptors within the striatum. The mechanism involved is dependent on the anaesthesia procedure which may act via enhancement of gamma-aminobutyric acidA (GABA(A)) mediated transmission within striatal and/or output neurones. In addition, anaesthesia may also decrease the activity of glutamatergic striatal afferents. The results with M35 indicate that the role of galanin perfused in striatum is permissive in the normal rat. Furthermore, galanin is a potent inhibitory modulator of basal ACh release also in the striatum, as recently was shown in the ventral hippocampus in awake animals.
Acetylcholine↗
Effect of morphine on dynorphin B and GABA release in the basal ganglia of rats.
In vivo microdialysis was used to study the effects of systemic, as well as intracerebral administration of morphine and naloxone on dynorphin B release in neostriatum and substantia nigra of rats. The release of dopamine (DA), gamma-aminobutyric acid (GABA), glutamate (Glu) and aspartate (Asp) was also investigated. Systemic injection of morphine (1 mg/kg s.c.) induced long-lasting increases in extracellular dynorphin B and GABA levels in the substantia nigra, whereas DA, Glu and Asp levels, measured in the same region, were not significantly affected. No effect on striatal neurotransmitter levels was observed following systemic morphine administration. Local perfusion of the substantia nigra with morphine (100 microM) through the microdialysis probe also increased nigral dynorphin B and GABA levels. Perfusion of the neostriatum with morphine (100 microM) significantly increased GABA and dynorphin B levels in the ipsilateral substantia nigra, but no effect was observed locally. Naloxone blocked the effect of systemic morphine administration on nigral dynorphin B and GABA release, already at a dose of 0.2 mg/kg s.c. Naloxone alone, given either systemically (0.2-4 mg/kg s.c.) or intracerebrally (1-100 microM), did not affect dynorphin B or amino acid levels, either in neostriatum or in substantia nigra. However, naloxone produced a concentration-dependent increase in DA levels. The present results indicate that systemic morphine administration stimulates the release of dynorphin B in the substantia nigra, probably by activating the mu-subtype of opioid receptor, since the effect of morphine on nigral dynorphin B and GABA was antagonized by a low dose of naloxone. The increase in extracellular DA levels produced by high concentrations of naloxone, both in neostriatum and substantia nigra, indicates a disinhibitory effect of this drug on DA release, probably via a non-mu subtype of opioid receptors located on nigro-striatal DA neurones.
Animals↗
Modulation of neurotransmitter release by cholecystokinin in the neostriatum and substantia nigra of the rat: regional and receptor specificity.
The effect of cholecystokinin peptides on the release of dynorphin B, aspartate, glutamate, dopamine and GABA in the neostriatum and substantia nigra of the rat was investigated using in vivo microdialysis. Sulphated cholecystokinin-8S in the dialysis perfusate (1-100 microM) induced a concentration-dependent increase in extracellular dynorphin B and aspartate levels, both in the neostriatum and substantia nigra. Striatal dopamine levels were only increased by 100 microM of cholecystokinin-8S, while in the substantia nigra they were increased by 10-100 microM of cholecystokinin-8S. Extracellular GABA and glutamate levels were increased following 100 microM of cholecystokinin-8S only. Striatal cholecystokinin-8S administration also produced a significant increase in nigral dynorphin B levels. Local cholecystokinin-4 (100 microM) produced a moderate, but significant, increase of extracellular dynorphin B and aspartate levels in the neostriatum and substantia nigra. No effect was observed on the other neurotransmitters investigated. A 6-hydroxydopamine lesion of the nigrostriatal dopamine pathway did not affect the increases in dynorphin B and aspartate levels produced by local administration of cholecystokinin-8S. Basal extracellular GABA levels were increased significantly in both the neostriatum and substantia nigra ipsilateral to the lesion. Nigral glutamate and aspartate levels were also increased in the lesioned substantia nigra, but in the lesioned neostriatum aspartate levels were decreased. The cholecystokinin-B antagonist L-365,260 (20 mg/kg, s.c.), but not the cholecystokinin-A antagonist L-364,718 (devazepide; 20 mg/kg, s.c.), significantly inhibited the effect of cholecystokinin-8S on striatal dynorphin B and aspartate levels. In the substantia nigra, however, the effect of cholecystokinin-8S on dynorphin B and aspartate levels was inhibited to a similar extent by both L-365,260 and L-364,718. Pretreatment with L-364,718, but not with L-365.260, prevented the increase in nigral dopamine levels produced by nigral cholecystokinin-8S administration. Taken together, these results suggest that cholecystokinin-8S modulates dynorphin B and aspartate release in the neostriatum and substantia nigra of the rat via different receptor mechanisms. In the neostriatum, the effect of cholecystokinin-8S on dynorphin B and aspartate release is mediated via the cholecystokinin-B receptor subtype, while in the substantia nigra, cholecystokinin-8S modulates dynorphin B and aspartate release via both cholecystokinin-A and cholecystokinin-B receptor subtypes. Cholecystokinin-8S modulates dopamine release mainly in the substantia nigra, via the cholecystokinin-A receptor subtype.
3,4-Dihydroxyphenylacetic Acid↗
Effects of ventral hippocampal galanin on spatial learning and on in vivo acetylcholine release in the rat.
The neuropeptide galanin coexists in the medial septum and diagonal band of Broca with a population of acetylcholine neurons which project mainly to the ventral hippocampus. The present studies investigated the role of ventral hippocampal galanin in spatial learning in the male rat using a spatial learning task. In addition, the effects of galanin on cholinergic function were monitored by in vivo microdialysis and high-performance liquid chromatography. Bilateral microinjections of galanin (3 nmol/ rat) via chronic cannulae placed into the ventral hippocampus (i.v.h.) produced a slight but significant impairment of acquisition of the spatial task, while the 1 nmol dose of galanin facilitated acquisition. The 6 nmol dose of galanin failed to affect performance. A trend for an impairment of long-term memory retention (examined seven days after the last training session) was observed after 3 nmol of galanin, while the 1 nmol dose facilitated retention performance. Scopolamine (0.1 mg/kg, s.c.) caused a marked impairment of acquisition. Galanin (3 nmol/rat) given i.v.h. failed to modify the acquisition impairment caused by scopolamine (0.1 mg/kg, s.c.). These results suggest that galanin given i.v.h. produces a biphasic dose-dependent effects on spatial learning. In freely moving rats, galanin (3 nmol/10 microliters) given into the lateral ventricle (i.c.v.) did not affect basal acetylcholine release. In contrast, perfusion (100 min) with galanin (0.1 or 0.3 nmol/1.25 microliters/min) through the ventral hippocampal probe resulted in a reduction of basal acetycholine release which was dose-dependent and reversible. Galanin given i.c.v. (3 nmol/10 microliters) or through the probe (0.3 nmol/1.25 microliters/min) attenuated the increase in acetylcholine release evoked by the muscarinic antagonist scopolamine (0.1 mg/kg, s.c.; 0.001 nmol/1.25 microliters/min through the probe). The galanin plus scopolamine combinations produced a 50% lower increase in the extracellular acetylcholine concentrations than scopolamine alone. This suggests that the mechanism(s) behind scopolamine- and galanin-induced stimulation of acetylcholine differ. These results indicate that ventral hippocampal galanin plays a role in cognition and that it has a powerful and modulatory effect on cholinergic transmission. However, the effects of exogenous galanin on spatial learning cannot be directly related to changes in in vivo cholinergic transmission in the ventral hippocampus. These discrepancies may relate to effects on subtypes of galanin receptors with different functional coupling. In addition, other hippocampal neurotransmitter systems (e.g. noradrenergic neurons) important for cognitive functions may also be modulated by ventral hippocampal galanin.
Acetylcholine↗
[Anorexigenic drugs in the treatment of obesity].
Obesity is highly prevalent and has several adverse effects on health. Its treatment is thus warranted and must aim to modify dietary and physical activity habits. The opinion of this association is that anorexigenic drugs with cathecolaminergic action (diethylpropion, phentermine, mazindol and phenylpropanolamine) or serotoninergic action (fenfluoramine and fluoxetine) may be used in moderate or severe obesity (BMI > 30 kg/m2) after a complete clinical assessment and in the context of an integral medical treatment. This association recommends a close surveillance of the use of these drugs, specially when formulated as non-proprietary prescriptions.
Appetite Depressants↗