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B H Westerink

Publications and source records attributed to B H Westerink.

At least 73 records · Page 4Linked to original sources
PubMed1994

A novel approach for studying septo-hippocampal cholinergic neurons in freely moving rats: a microdialysis study with dual-probe design.

In this study, the overflow of acetylcholine (ACh) in the septo-hippocampal system was studied using intracerebral microdialysis in freely moving rats. Dialysis probes were implanted in the ventral hippocampus and in the medial septal area (MS), including a part of the ventral limb of the diagonal band of Broca (VDB). Dialysis samples were analysed 'on-line' using HPLC with post column enzymatic conversion and electrochemical detection. Local perfusion of 1 mumol/l of the sodium-channel blocker tetrodotoxin (TTX) through the probe resulted in 94% and 92% decrease in extracellular levels of ACh in the hippocampus and the septal area, respectively. The effects of septal manipulation on the efflux of ACh in the hippocampus were studied by electrical stimulation of the septal area and by administering drugs via the septal probe. Electrical stimulation of the MS/VDB caused a 336% increase in the output of ACh in the hippocampus. Perfusion of 3 mumol/l TTX through the septal probe caused a maximal decrease of 56% in the output of ACh in the ventral hippocampus. When perfused in the MS/VDB, the excitatory amino-acid agonists N-methyl-D-aspartate (NMDA) (100 mumol/l) and kainic acid (10 mumol/l) caused an increase in the extracellular level of ACh in the hippocampus by 83% and 161%, respectively. Thus, the overflow of ACh in the hippocampus and the septal area both depend on neuronal impulse flow. The extracellular level of ACh in the hippocampus is at least partially dependent on impulse flow in septo-hippocampal fibres. Moreover, the output of ACh in the hippocampus can be manipulated by electrical and pharmacological stimulation of the MS/VDB.

Acetylcholine↗
PubMed1994

Do nerve terminals and cell bodies of nigrostriatal dopaminergic neurons of the rat contain similar receptors?

The question was investigated whether dopamine release-controlling receptors are evenly distributed over somatodendritic sites and nerve terminals of nigrostriatal dopaminergic neurons of the rat. Prototypical drugs of 5 different (sub)types of receptors (D2, cholinergic, GABAB, NMDA and non-NMDA) were infused via a microdialysis probe into the striatum, and effects on dopamine released from nerve terminals were determined by microdialysis. In separate experiments the same drugs were infused into the substantia nigra and effects on dendritic release of dopamine were recorded. In addition, the effect of calcium depletion and tetrodotoxin infusion (1 mumol/l) was studied in both areas. Infusion of (-)-N0437 (1 mumol/l), (-)-sulpiride (1 mumol/l), NMDA (300 mumol/l), AMPA (100 mumol/l), kainic acid (30 mumol), tetrodotoxin and depletion of calcium induced comparable changes in the release of dopamine when applied into the striatum as well as into the nigra. Carbachol (100 mumol/l) and baclofen (5 mumol/l) inhibited dendritic dopamine release when administered into the nigra; however, the latter drugs were not effective when infused into the striatum. It is concluded that the release-controlling receptors are not evenly distributed over somata and nerve terminals of dopaminergic neurons.

Animals↗
PubMed1994

Increase in dopamine release from the nucleus accumbens in response to feeding: a model to study interactions between drugs and naturally activated dopaminergic neurons in the rat brain.

The aim of the present study was to investigate the interactions between the in vivo release of dopamine and certain drugs, during conditions of increased dopaminergic activity. Dopaminergic neurons in the nucleus accumbens were activated by feeding hungry rats. 48-96 h after implantation of a microdialysis probe 30 min food ingestion by hungry rats induced an immediate eating response that was accompanied with a reproducible and long-lasting increase in extracellular dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC). The effect of various drugs (infused into the nucleus accumbens via the microdialysis probe), on the extracellular levels of dopamine and DOPAC were recorded, and the effect of eating was determined. Infusion of 5 mumol/l nomifensine and 3.4 mmol/l calcium increased dopamine release respectively 5.4 and 2-fold but did not modify the eating related increase in dopamine and DOPAC release. Infusion (1 mumol/l) as well as intraperitoneal administration (20 mg/kg) of sulpiride induced an increase in basal dopamine release to 220 and 195% of controls, respectively. Both routes of sulpiride pretreatment enhanced the eating related increase in extracellular dopamine and DOPAC. The results of the sulpiride experiments indicate that a behaviorally induced stimulation of dopamine release is modified by autoinhibition.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Subchronic treatment with the neuroleptic-like peptide desenkephalin-gamma-endorphin may decrease dopaminergic neurotransmission in the nucleus accumbens of rats.

In rats, subchronic administration of desenkephalin-gamma-endorphin (DE gamma E) into the nucleus accumbens or subcutaneously for 10 days resulted in hypoactivity. Intra-accumbens administration caused a significant reduction in the nucleus accumbens tissue levels of the dopamine (DA) metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Systemic administration of DE gamma E decreased DOPAC and 5-hydroxyindoleacetic acid (5-HIAA) levels in nucleus accumbens tissue. Subchronic subcutaneous DE gamma E treatment reduced the basal release of [3H]DA from rat nucleus accumbens slices in vitro and the basal release of endogenous DA and DOPAC in vivo as assessed with on-line dialysis in the nucleus accumbens of freely moving rats. The DA agonist N,N-dipropyl-7-hydroxy-2-aminotetralin (DP-7-ATN) was equally effective in inhibiting [3H]DA release elicited by electrical stimulation from slices of subchronically DE gamma E and placebo treated rats. Administration of a small dose of apomorphine caused similar reductions of the in vivo release of DA and DOPAC in both placebo and DE gamma E treated rats. These results indicate that subchronic DE gamma E treatment may decrease dopaminergic neurotransmission in the nucleus accumbens. This effect is probably not due to alterations in the sensitivity of presynaptically located DA autoreceptors mediating DA release in vitro and in vivo.

Animals↗
PubMed1994

GABAergic modulation of striatal cholinergic interneurons: an in vivo microdialysis study.

Striatal cholinergic interneurons have been shown to receive input from striatal gamma-aminobutyric acid (GABA)-containing cell elements. GABA is known to act on two different types of receptors, the GABAA and the GABAB receptor. Using in vivo microdialysis, we have studied the effect of intrastriatal application of the GABAA-selective compounds muscimol and bicuculline and the GABAB-selective compounds baclofen and 2-hydroxysaclofen, agonists and antagonists, respectively, at GABA receptors, on the output of striatal acetylcholine (ACh). Intrastriatal infusion of 1 and 10 mumol/L concentrations of the GABAA antagonist bicuculline resulted in a significant increase in striatal ACh output, whereas infusion of 1 and 10 mumol/L concentrations of the GABAA agonist muscimol significantly decreased the output of striatal ACh. Both compounds were ineffective in changing the output of striatal ACh at lower concentrations. Infusion of concentrations up to 100 mumol/L of the GABAB-selective antagonist 2-hydroxy-saclofen failed to affect striatal ACh output, whereas infusion of 10 and 100 mumol/L baclofen, but not 0.1 and 1 mumol/L baclofen, significantly decreased the output of striatal ACh. Thus, agonist-stimulation of GABAA and GABAB receptors decreases the output of striatal ACh in a dose-dependent fashion, whereas the GABAAergic system appears to inhibit tonically the output of striatal ACh via GABAA receptors, but not via GABAB receptors. We hypothesize that although GABAA mediated regulation of striatal ACh occurs via GABA receptors on the cholinergic neuron, the GABAB mediated effects may be explained by presynaptic inhibition of the glutamatergic input of the striatal cholinergic neuron.

Acetylcholine↗
PubMed1993

Are bilateral nigrostriatal dopaminergic pathways functionally linked in the rat brain? A microdialysis study in conscious rats.

In the present study, we have infused 6 prototypical drugs known to affect nigrostriatal dopaminergic neurons (kainate, baclofen, muscimol (10 mumol/l), picrotoxin (50 mumol/l), tetrodotoxin (TTX) (5 mumol/l) and 1-methyl-4-phenylpyridinium ion (MPP+) (10 mmol/l) via a microdialysis probe unilaterally into the left substantia nigra. During the infusion of these compounds, the extracellular content of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) was recorded simultaneously via microdialysis cannulas in both left and right striatum. Intranigral infusion of TTX, MPP+ and baclofen decreased dopamine release in the ipsilateral striatum, whereas muscimol, picrotoxin and kainate increased dopamine release. No changes were seen in the extracellular content of dopamine in the contralateral striatum. During all experiments, extracellular DOPAC increased in the ipsilateral striatum. No changes were seen in the extracellular content of DOPAC in the contralateral striatum. The present data provide no evidence that the bilateral nigrostriatal dopaminergic pathways are functionally linked in the rat brain.

1-Methyl-4-phenylpyridinium↗
PubMed1993

Pharmacological aspects of R-(+)-7-OH-DPAT, a putative dopamine D3 receptor ligand.

The R-(+)-isomer of 7-hydroxy-2-(N,N-di-n-propylamino)tetralin (7-OH-DPAT) bound with a more than 200-fold higher affinity to cloned human dopamine D3 receptors (Ki = 0.57 nM) than to dopamine D2 receptors; the corresponding S-(-)-enantiomer had considerably less affinity for both dopamine receptor subtypes, indicating that the known enantiomer selectivity of 7-OH-DPAT for the 'classical' dopamine D2 receptor subtype extends to the recently discovered dopamine D3 receptor subtype. In rats R-(+)-7-OH-DPAT dose dependently (10-1000 nmol/kg) decreased dopamine release and induced yawning, while sniffing behaviour occurred at the highest dose tested (1000 nmol/kg). The possibility that the inhibition of dopamine release and the elicitation of yawning are mediated by dopamine D3 receptors is considered.

Animals↗
PubMed1993

Differential effect of systemic administration of bromocriptine and L-dopa on the release of acetylcholine from striatum of intact and 6-OHDA-treated rats.

A presumed balance between striatal dopaminergic and cholinergic systems forms a major theoretical framework for the development of new agents for the treatment of Parkinson's disease. We therefore studied the effect of two drugs currently used as anti-parkinsonian agents, bromocriptine (BROMO) and L-beta-3,4-dihydroxyphenylalanine (L-DOPA), on the release of striatal acetylcholine (ACh) in intact and 6-hydroxy-dopamine-treated rats using in vivo microdialysis. Lesioned rats with a > 90% tissue depletion of striatal dopamine (DA) had a significantly higher output of striatal ACh than unlesioned rats (88 fmol/min vs. 52 fmol/min; 0.3 mumol/l neostigmine in perfusate). BROMO (4 mg/kg) inhibited the output of striatal ACh in both groups. Whereas the lowest dose of L-DOPA (50 mg/kg) potently stimulated ACh output in lesioned rats, unlesioned rats were significantly less responsive. A higher dose of L-DOPA (100 mg/kg) stimulated ACh output to the same extent in both groups. At the highest dose tested, L-DOPA (200 mg/kg) given to intact rats did not further increase striatal ACh output. Thus, BROMO decreases whereas L-DOPA increases striatal ACh release after systemic application. Therapeutic as well as side effects of L-DOPA may therefore be mediated by neurochemical alterations that are more complex than previously thought.

Acetylcholine↗
PubMed1993

Microdialysis of melatonin in the rat pineal gland: methodology and pharmacological applications.

The present study describes the development of a new technique to measure melatonin contents in the pineal gland of freely moving rats, by means of on-line microdialysis. The transcerebral cannula was modified, and a sensitive assay of melatonin, using HPLC with fluorimetric detection, was set up. With this system it is possible to monitor the melatonin levels on-line in the pineal gland during day- and nighttime. The nightly increase in melatonin release was recorded. Tetrodotoxin had an inhibitory effect on nighttime levels, whereas even high concentrations did not alter the daytime level. From this we conclude that neuronal activity is necessary to synthesize melatonin and that during daytime no net neuronal activity is present. Melatonin levels could be greatly enhanced by systemic administration of the beta-agonist isoprenaline (ISO). Also, local infusion of ISO or 8-bromoadenosine 3',5'-cyclic monophosphate, an analogue of the second messenger cyclic AMP, resulted in increased melatonin levels, demonstrating the presence of beta-adrenergic receptors, coupled to a cyclic AMP-based second messenger system, on the pineal gland. Injection of phenylephrine had no effect on daytime levels. Only when administered during ISO-induced stimulation of melatonin release did it enhance this stimulated release. This proved the regulatory role of alpha 1-receptors on pinealocytes. The method presented is of special interest for investigating the innervation of the pineal gland and the biochemical processes that regulate the biosynthesis of melatonin. Also, for studies on the diurnal rhythms of melatonin release and factors that influence these rhythms in freely moving animals, this model will be of great value.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1992

The role of GABA receptors in the control of nigrostriatal dopaminergic neurons: dual-probe microdialysis study in awake rats.

A microdialysis probe implanted into the substantia nigra was used to infuse gamma-aminobutyric acid-ergic (GABAergic) compounds onto cell bodies/dendrites of dopaminergic neurons, while a second microdialysis probe was used to record the extracellular concentrations of dopamine and 3,4-dihydroxy-phenylacetic acid (DOPAC) in the ipsilateral striatum. The GABAA receptor agonist muscimol (10 mumol/l) increased the release of dopamine in the ipsilateral striatum to 120% of the control values. The GABAB receptor agonist, (Z)-3[(aminoiminomethyl)-thiol]-prop-2- enoic acid (500 mumol/l), was without effect. Infusion of the GABAA receptor antagonists, bicuculline (50 mumol/l) and picrotoxin (50 mumol/l), stimulated the release of dopamine in the ipsilateral striatum to 160 and 130% of the controls, respectively. The GABAB receptor agonist, baclofen (10 and 50 mumol/l), strongly inhibited the release of striatal dopamine, whereas infusion of the GABAB receptor antagonist, 2-hydroxy-saclofen (100 mumol/l), was without effect. The results indicate that, in the substantia nigra, GABAA as well as GABAB receptors participate in controlling the activity of dopaminergic neurons.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Raised glucose levels enhance scopolamine-induced acetylcholine overflow from the hippocampus: an in vivo microdialysis study in the rat.

Behavioural studies in both humans and animals have shown that an acute rise in circulating glucose levels at or around the time of training enhances subsequent retention performance and can also afford protection from the amnesia produced by posttraining injections of scopolamine. In an attempt to directly investigate the neurochemical basis for these effects of glucose we have tested the hypothesis that raised glucose levels may enhance acetylcholine (ACh) synthesis and release in the brain during conditions of increased neuronal activity, induced either by training or pharmacological challenge, via a microdialysis study using rats. Microdialysate concentrations of ACh overflow from the hippocampus of fasted rats induced by i.p. injections of scopolamine (1 mg/kg) combined with concurrent s.c. injections of either glucose (2 g/kg) or saline were compared in successive 15-min samples using an on-line HPLC system. Scopolamine injections resulted in an immediate 10-20-fold increase in hippocampal ACh overflow which subsequently progressively declined over a 4-h period to pretreatment baseline levels. The combined injection of glucose with scopolamine resulted in a highly significant enhancement (19.4%; P less than 0.01) in ACh content of the first two samples as compared to saline-injected controls. These results provide the first direct experimental evidence that raised glucose levels, via increased availability of acetyl-coenzyme A (acetyl-coA), transiently facilitates ACh synthesis and release during conditions of increased neuronal activity. This enhancement of ACh availability during states of cholinergic neuronal activation may underlie the previously observed facilitatory effects of glucose on memory performance and its protection from scopolamine-induced amnesia.

Acetylcholine↗
PubMed1992

Characterization of extracellular GABA in the substantia nigra reticulata by means of brain microdialysis.

Brain microdialysis was used to characterize extracellular gamma-aminobutyric acid (GABA) in the substantia nigra reticulata (SNR) of freely moving rats. The extracellular GABA in the SNR was characterized using acutely implanted probes (4-8 h after surgery; day 1) and chronically implanted probes (24 h after surgery; day 2). 3-Mercaptopropionic acid, a glutamic acid decarboxylase inhibitor, was used to identify GABA. This drug induced an immediate decrease in the extracellular GABA levels to 40% of basal values, suggesting that the detected GABA is, at least in part, newly synthesized. The basal levels of extracellular GABA measured either on day 1 or day 2 were not affected by infusion of micromolar amounts of tetrodotoxin. Therefore, a direct coupling between GABA dialysate concentrations and nerve-impulse flow does not seem to exist. Infusion of the GABA uptake inhibitor nipecotic acid (0.5 mmol/l) resulted in a 4-fold increase in the dialysate levels of GABA lasting at least for 3 h on both days. K+ stimulation (60 mmol/l) increased extracellular GABA levels in the SNR to 450% of basal values. This effect again did not differ significantly on day 1 and day 2. The origin of the extracellular GABA in the SNR, as recorded by microdialysis under the two experimental conditions, is discussed.

3-Mercaptopropionic Acid↗
PubMed1992

The effect of intrastriatal application of directly and indirectly acting dopamine agonists and antagonists on the in vivo release of acetylcholine measured by brain microdialysis. The importance of the post-surgery interval.

The effect of intrastriatal application of D-1, D-2 and indirect dopaminergic drugs on the release of striatal acetylcholine as a function of the post-implantation intervals was studied using in vivo microdialysis. The dopamine D-2 agonists LY 171555 and (-)N0437 inhibited the release of striatal acetylcholine to 40% of control values 16-24 h after implantation of the dialysis cannula. When LY 171555 was infused 40-48 h after implantation of the dialysis cannula, the response was attenuated to 20% of control values. Meanwhile, the effectiveness of infusions of the antagonists (-)sulpiride and haloperidol was augmented from a non significant effect at 16-24 h to a 150% increase 40-48 h after implantation of the cannula. Infusions of the dopamine releasing agent amphetamine or the dopamine uptake inhibitor nomifensine resulted in a dose-dependent increase in the overflow of dopamine. Not until a sevenfold increase in the level of dopamine was seen, the release of acetylcholine was significantly affected. This hyporesponsiveness of the striatal cholinergic interneurons to endogenous dopamine could not be attributed to dopamine D-1 receptor activation, since no effects on striatal acetylcholine release were found by intrastriatal infusions of the selective D-1 agonist CY 208-243 or the selective D-1 antagonist SCH 23390. The results indicate that dopamine D-2 receptors are involved in the regulation of striatal acetylcholine release and that these receptors are tonically occupied by endogenous dopamine under the present experimental conditions 40-48 h after probe implantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1992

In vivo evidence for a concordant response of terminal and dendritic dopamine release during intranigral infusion of drugs.

In the present study we have administered prototypical drugs of 5 different receptors (D-2, GABA-A, GABA-B, NMDA, kainate) to the substantia nigra by infusion via a microdialysis probe, whereas the release of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) were recorded both in the substantia nigra and (by a second microdialysis probe) in the ipsilateral striatum. Infusion of the specific D-2 receptor agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin ((--)-N0437) into the nigra induced a decrease in the release of dopamine in the nigra (after 1 mumol/l) as well as in the ipsilateral striatum (after 10 mumol/l). During these infusions extracellular DOPAC decreased in the nigra and increased in the striatum. Infusion of the D-2 specific receptor antagonist (--)-sulpiride into the nigra induced an increase in the release of dopamine in the nigra (after 1 mumol/l) as well as in the ipsilateral striatum (10 mumol/l). During these infusions a slight increase of extracellular DOPAC was noticed in the nigra. Infusion of the GABA-A receptor antagonist bicuculline into the nigra (50 mumol/l) induced an increase in the release of dopamine and DOPAC both in the nigra and ipsilateral striatum. Infusion of the GABA-B receptor agonist d,I-baclofen into the nigra (10 mumol/l) induced a decrease of in the release of dopamine in the nigra as well as in the ipsilateral striatum, whereas extracellular DOPAC decreased in the nigra and increased in the striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

The release of dopamine from nerve terminals and dendrites of nigrostriatal neurons induced by excitatory amino acids in the conscious rat.

The possible localization of excitatory amino acid (EAA) receptors on dopaminergic neurons was studied by microdialysis in conscious male rats. Varying concentrations of 3 specific EAA agonists, N-methyl-D-aspartate (NMDA), kainate and amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), were infused into the striatum or into the substantia nigra, and the extracellular dopamine (DA) was recorded by the same probe. All 3 compounds induced a dose-dependent increase in both striatal and nigral extracellular DA. Kainate and AMPA were more potent than NMDA. Nigral DA release was stimulated by lower concentrations of kainate and AMPA than striatal DA release. The effects of two concentrations of NMDA and kainate on the release of DA were analyzed in terms of tetrodotoxin (TTX) dependency and sensitivity to ibotenic acid-induced striatal lesion. It appeared that NMDA and kainate stimulated DA release by 3 different mechanisms. The first mechanism is seen at low concentrations of kainate, it fulfills the criteria for a functional receptor-interaction: it is TTX-sensitive and independent of the ibotenic acid lesion. The second mechanism was observed when relatively low concentrations of NMDA stimulate the release of DA; in this effect postsynaptic structures are involved. The third mechanism lacks specificity as it is seen after high concentrations of kainate as well as of NMDA. The latter mechanism is TTX-independent and is probably of a toxic nature. Finally NMDA and kainate were infused into the nigra, whereas DA was recorded with a second probe implanted into the striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1992

Simultaneous recording of the release of nigral and striatal dopamine in the awake rat.

The extracellular concentration of dopamine (DA) and 3,4-hydroxyphenylacetic acid (DOPAC) were estimated in the substantia nigra and striatum by microdialysis. The dialysate content of DA increased at least 10-fold when nomifensine (5 mumol/l) was infused into the nigra via the dialysis membrane. To improve the analytical chemical detection of DA, nomifensine was infused continually during all the dialysis experiments that were carried out in the substantia nigra. Dendritic as well as terminal release of DA were inhibited for several hours when the nerve impulse flow in dopaminergic neurons was blocked by systemic administration of gamma-butyrolacton (750 mg/kg, i.p.). Perfusion of tetrodotoxin through the nigra (1 mumol/l) produced a complete disappearance of nigral DA release and a somewhat variable decrease in the release of striatal dopamine. When tetrodotoxin was infused into the nigra, the DOPAC output from the nigra was unchanged, but striatal DOPAC increased to about 300% of controls. These results show that the dendritic release of DA fulfills classical release criteria: it possesses an effective uptake-mechanism, it is dependent on the opening of fast-sodium channels and it is related to drug-induced changes in impulse-flow activity.

3,4-Dihydroxyphenylacetic Acid↗