Biomedical subjects

B H Westerink

Publications and source records attributed to B H Westerink.

At least 55 records · Page 3Linked to original sources

PubMed1997

A microdialysis study on pineal melatonin rhythms in rats after an 8-h phase advance: new characteristics of the underlying pacemaker.

This study describes the use of the microdialysis technique to elucidate specific properties of the circadian pacemaking system in the hypothalamus, by measurement of melatonin production in the pineal gland. Melatonin has appeared to be a reliable marker of the pacemaker activity, which is influenced by the light/dark cycle. A phase shift in the light/dark cycle was applied to perturb the rhythm generating system. An 8-h phase advance resulted in the disappearance of melatonin production over two days, with basal levels comparable to normal daytime levels. In the subsequent return of rhythmic melatonin production, new clock characteristics could be revealed, due to the high time-resolution measurements of microdialysis. While half of the animals still did not show any rhythmicity, the other half of the animals regained rhythmicity with entrained onset of melatonin production, while the offset was variable and not stably entrained to lights on. Ten days after the shift, the system had completely recovered and all animals regained normal rhythmicity, in phase with the new light/dark cycle. The results are interpreted in terms of the two-oscillator model, with one oscillator reacting with a phase advance and the other with a phase delay to adapt to the phase shift.

Animals↗

PubMed1997

Eating-induced dopamine release from mesolimbic neurons is mediated by NMDA receptors in the ventral tegmental area: a dual-probe microdialysis study.

This study was aimed at identifying the neuronal pathways that mediate the eating-induced increase in the release of dopamine in the nucleus accumbens of the rat brain. For that purpose, a microdialysis probe was implanted in the ventral tegmental area and a second probe was placed in the ipsilateral nucleus accumbens. Receptor-specific compounds acting on GABA(A) (40 microM muscimol; 50 microM bicuculline), GABA(B) (50 microM baclofen), acetylcholine (50 microM carbachol), NMDA [30 microM (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP)], and non-NMDA [300 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)] receptors were infused into the ventral tegmental area by retrograde dialysis, whereas extracellular dopamine was recorded in the ipsilateral nucleus accumbens. Intrategmental infusion of muscimol or baclofen decreased extracellular dopamine in the ipsilateral nucleus accumbens; CPP and CNQX were without effect, and bicuculline and carbachol increased dopamine release. During infusion of the various compounds, food-deprived rats were allowed to eat for 10 min. The infusions of muscimol, bicuculline, baclofen, carbachol, and CNQX did not prevent the eating-induced increase in extracellular dopamine in the nucleus accumbens. However, during intrategmental infusion of CPP, the eating-induced increase in extracellular dopamine in the nucleus accumbens was suppressed. These results indicate that a glutamatergic projection to the ventral tegmental area mediates, via an NMDA receptor, the eating-induced increase in dopamine release from mesolimbic dopamine neurons.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1997

Use of microdialysis for monitoring sympathetic and parasympathetic innervation of heart in conscious rats.

A microdialysis method was developed to sample norepinephrine and acetylcholine from the heart of freely moving rats. A flexible dialysis fiber (length 14 mm), with a copper wire inserted inside, was implanted into the heart. Extracellular norepinephrine was detectable for at least 72 h after implantation. Basal output levels 24 h after surgery were 140 pg/ml when corrected for in vitro recovery. Evidence was provided that the major part of norepinephrine in dialysates is derived from local neurotransmission. Acetylcholine was only detectable in cardiac dialysates when an esterase inhibitor was infused. Corrected basal output levels 24 h after surgery were 223 pg/ml when neostigmine was coinfused in a concentration of 100 mumol/l. In addition, the presence of local muscarinic autoreceptors on cholinergic neurons in the heart was shown. It is concluded that microdialysis is a reliable method that can be used to study the innervation of the heart in subchronic preparations in freely moving rats.

Acetylcholine↗

PubMed1996

Parasympathetic inhibition of pineal indole metabolism by prejunctional modulation of noradrenaline release.

The role of the parasympathetic nervous system in rat pineal indole metabolism was investigated by transpineal in vivo microdialysis. On-line coupling to a high performance liquid chromatography system with fluorescence detection (HPLC-FD) allowed simultaneous analysis of three major indolic compounds from the pineal, i.e. serotonin, N-acetylserotonin and melatonin. Infusion of the muscarinic receptor agonists, carbachol and oxotremorine, during the dark period resulted in a marked decrease of melatonin release. This effect was suggested to be mediated by a decrease in N-acetyltransferase activity, since a similar decrease was seen in N-acetylserotonin release, while serotonin levels increased simultaneously. Nicotine did show a very slight effect on the three indoles under these circumstances. Neostigmine failed to influence pineal indole metabolism, indicating that the endogenous tonus of acetylcholine release is either absent or extremely low in the middle of the dark period. The involvement of sympathetic innervation in the muscarinic effects was investigated by measurement of noradrenaline release from the pineal by sensitive off-line HPLC-FD analysis of noradrenaline in the dialysates. Carbachol markedly decreased the noradrenaline input during the infusion. Noradrenaline release returned to baseline values immediately after infusion with carbachol. These data suggest that the in vivo inhibitory effect of muscarinic receptor agonists on pineal melatonin production is mediated by presynaptic muscarinic receptors, located on the sympathetic nerve endings. This prejunctional inhibition of noradrenaline release causes a reduced induction of N-acetyltransferase activity, resulting in decreased melatonin release.

Animals↗

PubMed1996

The pharmacology of mesolimbic dopamine neurons: a dual-probe microdialysis study in the ventral tegmental area and nucleus accumbens of the rat brain.

Receptor-specific compounds were applied by retrograde microdialysis to the ventral tegmental area (VTA) of the rat brain. The effect of the intrategmental infusions on extracellular dopamine in the ipsilateral nucleus accumbens were recorded with a second microdialysis probe. Intrategmental infusion of muscimol (10-40 microM) or baclofen (50 microM) decreased extracellular dopamine in the nucleus accumbens. Intrategmental infusion of NMDA (1 mM, 15 min) or kainate (50 microM, 15 min) increased extracellular dopamine in the nucleus accumbens. The effects of the excitatory amino acids were suppressed by co-infusion of MK-801 (1 MM), (+)-3-amino-1-hydroxy-2-pyrrolidone [(+)-HA966; 1 mM], (+/-)-3(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 100 microM), and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX;300 microM). Intrategmental infusion of of carbachol (50 microM) increased extracellular dopamine in the nucleus accumbens. These results provide evidence for localization of GABAA, GABAB NMDA, non-NMDA, and cholinergic receptors on dopamine neurons in the VTA. Infusions of CPP, (+)-MK-801, (+)-HA966, CNQX, mecamylamine, atropine, or 3-[[(3,4-dichlorophenyl)methyl]propyl](diethoxymethyl) phosphonic acid (CGP 52432) into the VTA did not modify extracellular dopamine in the nucleus accumbens. Infusion of bicuculline (50 microM) and (-)-sulpiride (50 microM) was followed by an increase in extracellular dopamine in the nucleus accumbens. These data suggest that dopamine neurons in the VTA are tonically inhibited by GABA and dopamine by acting on GABAA, and D2 receptors, respectively. A tonic stimulation by glutamatergic or cholinergic neurons was not detected. Finally, results on A10 neurons are compared with earlier data on A9 neurons. A striking difference was found in that GABAA-dopamine interactions are indirect in the substantia nigra and direct in the VTA.

Animals↗

PubMed1996

Microdialysis reveals dynamics of coupling between noradrenaline release and melatonin secretion in conscious rats.

The coupling between noradrenergic innervation of the pineal gland and melatonin production was investigated. Previously, the development of a microdialysis technique was described which made it possible to study the noradrenaline (NA) input as well as the melatonin output with high time resolution. In the present study, we studied the effects of short-term changes in NA-release on melatonin secretion. A 1 min light pulse was applied around midnight and resulted in an immediate decrease of both NA and melatonin. While NA returned to basal levels in 40 min, melatonin did not reach the baseline within 2.5 h. This discrepancy in correlation between NA and melatonin indicates a rapid inactivation of N-acetyl-transferase (NAT), followed by a slow reactivation, possibly by de novo synthesis of NAT. During daytime, a perfusion with 60 mM potassium for 30 min, resulted in a rapid and short stimulation of NA release, which was not followed by an increase in melatonin production. This indicates that 30 min stimulation of NAT activation is not enough to increase the amount of melatonin produced. The combination of measuring NA input and melatonin output appears to be a valuable tool in studying the characteristics of pineal activity in great detail.

Animals↗

PubMed1996

Norepinephrine release in the rat pineal gland: the input from the biological clock measured by in vivo microdialysis.

The sympathetic innervation of the rat pineal gland was investigated, measuring the norepinephrine (NE) release by on-line in vivo microdialysis. NE was assayed using an HPLC method with precolumn derivatization and fluorescence detection. Its high sensitivity and reliability made it very suitable to monitor the low levels of NE in the dialysates (12.5 fmol during nighttime, 3 fmol during daytime). To increase NE levels, the monoamine reuptake inhibitor cocaine was added to Ringer's solution at concentrations of 10(-6) and 10(-5) M. This resulted in increases of neurotransmitter output of 167 and 219%, respectively, but did not change the qualitative and/or quantitative outcome of other experiments. Perfusion with 10(-6) M tetrodotoxin for 1 h resulted in a decrease of the NE release by >80%, whereas perfusion with the alpha 2-receptor antagonist yohimbine caused a twofold increase. These results indicate that the NE release in the rat pineal was of neuronal origin and regulated by a negative feedback mechanism involving inhibitory presynaptic alpha 2-receptors. Long-term (i.e., 16 h) measurements are described, showing the circadian properties of NE release. A pronounced rhythm is reported, showing extremely sharp transitions between low daytime and high nighttime values. Increases and decreases are reported to occur within the duration of collecting one sample (20 min). For comparison, the rhythm of melatonin release was also recorded. The on and off switches of the sympathetic input correlated well with the circadian rhythm of melatonin release and can thus be considered as the primary clock signal, inducing the nightly production of melatonin.

Adrenergic alpha-Antagonists↗

PubMed1996

Septal and hippocampal glutamate receptors modulate the output of acetylcholine in hippocampus: a microdialysis study.

In the present study, glutamate receptor agonists and antagonists were administered by retrograde microdialysis into either the medial septum/vertical limb of the diagonal band (MS/vDB), or hippocampus, and the output of acetylcholine (ACh) was measured in the hippocampus by using intracerebral microdialysis. Perfusion with N-methyl-D-aspartate (NMDA) and (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) in the MS/vDB caused an incrase in ACh output in the hippocampus. This increase was completely blocked by coadministration of their respective antagonists D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Perfusion in the MS/vDB with kainic acid also caused an increase in ACh output, but coadministration of CNQX attenuated the increase only partially. Perfusion with D-AP5 and CNQX alone in the septal probe did not affect ACh output from the hippocampus. In contrast to the results of septal administration of NMDA and AMPA, local perfusion with the same drugs in the hippocampus caused a decrease in ACh output. Whereas the results of septal administration of drugs indicate that septal cholinergic neurons probably receive excitatory glutamatergic innervation, the decrease in ACh output caused by administration of NMDA and AMPA in the hippocampus is poorly understood.

2-Amino-5-phosphonovalerate↗

PubMed1996

Excitatory amino acid receptors in the ventral tegmental area regulate dopamine release in the ventral striatum.

The role of excitatory amino acid (EAA) receptors located in the ventral tegmental area (VTA) in tonic and phasic regulation of dopamine release in the ventral striatum was investigated. Microdialysis in conscious rats was used to assess dopamine release primarily from the nucleus accumbens shell region of the ventral striatum while applying EAA antagonists or agonists to the VTA. Infusion of the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (25 and 100 microM) into the VTA did not affect dopamine release in the ventral striatum. In contrast, intra-VTA infusion of the NMDA receptor antagonist 2-amino-5-phosphopentanoic acid (100 and 500 microM) dose-dependently decreased the striatal release of dopamine. Intra-VTA application of the ionotropic EAA receptor agonists NMDA and AMPA dose-dependently (10 and 100 microM) increased dopamine efflux in the ventral striatum. However, infusion of 50 or 500 microM trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD), a metabotropic EAA receptor agonist, did not significantly affect these levels. These data suggest that NMDA receptors in the VTA exert a tonic excitatory influence on dopamine release in the ventral striatum. Furthermore, dopamine neurotransmission in this region may be enhanced by activation of NMDA and AMPA receptors, but not ACPD-sensitive metabotropic receptors, located in the VTA. These data further suggest that EAA regulation of dopamine release primarily occurs in the VTA as opposed to presynaptically at the terminal level.

Animals↗

PubMed1996

Exogenous melatonin entrains rhythm and reduces amplitude of endogenous melatonin: an in vivo microdialysis study.

The circadian rhythm of melatonin production was studied using on-line, in vivo microdialysis in the rat pineal gland. With this technique it was possible to record a pronounced melatonin rhythm with very high time resolution. Three phase-markers of the rhythm were calculated from the data, indicating increase (IT50), decrease (DT50) and amplitude of the rhythm. Comparing these phase markers led to several conclusions. Entrainment of the rhythm under constant darkness was performed with melatonin administration at different circadian stages [circadian time (CT) 8 and CT12] and for different periods of time (2 weeks and 4 weeks). Also, entrainment was established by applying 15 min light pulses at CT0. Entrainment of IT50 with melatonin partially uncoupled it from DT50. Four weeks entrainment in constant darkness (DD) caused a phase-delay in DT50 of 2.2 hr. Entrainment of IT50 with light at CT0 for 2 weeks in DD caused a phase-advance in DT50 of 1.3 hr. The entrainment with melatonin was restricted to a narrow window for melatonin to be applied, since injections at CT8 did not result in entrainment. Exogenous melatonin reduced the amplitude of the rhythm of endogenous melatonin. This effect was not circadian time dependent, since administration at CT8 for 2 weeks and at CT12 for 4 weeks resulted in a highly significant decrease. Light did not seem to have an effect on the amplitude. The data presented here provide us with new information about the nature of entrainment by melatonin. Since the present development of melatonergic agents for clinical use focuses on the entrainment capacity, effects of these compounds on amplitude of circadian rhythms needs to be addressed. In vivo microdialysis seems to be a good technique for that.

Animals↗

PubMed1996

GABA receptors in the region of the dorsomedial hypothalamus of rats are implicated in the control of melatonin and corticosterone release.

Recently, anatomical evidence was presented that the mammalian circadian clock located in the suprachiasmatic nuclei (SCN) may utilize GABA to transmit diurnal information to the dorsomedial hypothalamus (DMH). The present study provides further physiological evidence for the involvement of this GABAergic projection in the regulation of diurnal rhythms. Infusion of the GABA agonist muscimol in the region of the DMH completely blocked the daily increase of plasma melatonin during darkness and reduced sympathetic output in the pineal gland resulting in lower pineal melatonin production, as measured with transpineal microdialysis. Further experiments in SCN-lesioned animals indicated that the origin of this inhibitory input to the DMH is indeed the SCN. The results of this study imply that the SCN can influence the sympathetic outflow of the hypothalamus through its GABA-containing projection. Furthermore, the present results probably explain the previously reported strong inhibitory effect of benzodiazepines on plasma melatonin in both animals and humans.

Animals↗

PubMed1995

Characterisation of muscarinic autoreceptors in the septo-hippocampal system of the rat: a microdialysis study.

The effects of local administration of cholinergic drugs on the release of acetylcholine in the septo-hippocampal system were investigated using intracerebral microdialysis. Dialysis probes were implanted in the cell-body area of septo-hippocampal neurones in the medial septal area, and in the terminal area of the same neurones in the ventral hippocampus. Drugs were administered locally via the dialysis probe. Administration of the mixed muscarinic/nicotinic receptor agonist carbachol caused a decrease, whereas administration of the muscarinic receptor antagonist methyl-atropine caused an increase in the output of acetylcholine in both the hippocampus and the medial septal area. In contrast, perfusion with the same drugs and the acetylcholine esterase inhibitor neostigmine bromide in the septal area had little or no effect on the output of acetylcholine in hippocampus. The results indicate that acetylcholine autoreceptors are localised on nerve terminals in medial septal area and hippocampus, and exert an inhibitory control over acetylcholine release. However, autoreceptors seem to be sparse or absent on dendrites and cell bodies of septo-hippocampal cholinergic neurones.

Acetylcholine↗

PubMed1995

Extracellular gamma-aminobutyric acid in the substantia nigra reticulata measured by microdialysis in awake rats: effects of various stimulants.

The gamma-aminobutyric acid (GABA)-ergic system in the substantia nigra reticulata (SNR) was challenged by local infusion of various receptor-specific agents to obtain additional information on the physiological significance of extracellular GABA levels as measured by microdialysis in awake rats. Notwithstanding in vitro results, basal extracellular GABA levels were not affected by local infusion of the GABA-A agonist muscimol or by infusion of the GABA-B agonist baclofen. Upon a dopaminergic challenge, the D2 agonist LY 171555 was equally ineffective, but the D1 agonist induced an increase in extracellular GABA levels, which persisted in the presence of tetrodotoxin (TTX). Using excitatory amino acids, kainic acid was ineffective in modulating GABA levels, whereas N-methyl-D-aspartate induced an increase in extracellular GABA levels, again persisting when co-infused with TTX. The functional significance of TTX-independent changes in extracellular GABA levels is discussed.

Animals↗

PubMed1995

Lack of evidence for dopamine autoreceptors in the mediobasal hypothalamus: a microdialysis study in awake rats.

To determine the functional presence of dopamine (DA) autoreceptors on tuberoinfundibular dopamine (TIDA)-ergic neurons in awake rats, a microdialysis probe was implanted into the mediobasal hypothalamus (MBH). In the presence of the re-uptake inhibitor nomifensine, which increased DA levels to 350% of basal values, systemic administration of the non-selective D1/D2 antagonist haloperiol induced an immediate increase in DA and DOPAC levels to 145% of pretreatment values. However, neither local infusion of the selective D2 antagonist sulpiride nor of the D1 antagonist SCH 23390 affected the nomifensine-elevated extracellular DA or DOPAC levels in the MBH. Systemic administration of the D2 antagonist raclopride equally did not affect the nomifensine-elevated DA release in the MBH. Upon basal extracellular DA levels (without nomifensine), local infusion of the D2 agonist (-)N-0437 equally did not affect the DA or DOPAC levels in the MBH. Furthermore, the increase in DA levels induced by haloperidol could not be antagonized by the D1 agonist CY 208-243. Therefore, the present study does not provide support for the concept of functional autoreceptors located on TIDA neurons regulating the release of DA. Possibly, the effect of haloperidol was non-DA-ergic in character.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1995

The significance of extracellular GABA in the substantia nigra of the rat during seizures and anticonvulsant treatments.

The effects of the anti-epileptic drugs valproic acid and gamma-vinyl-GABA (vigabatrin) on the extracellular content of GABA was determined by microdialysis. Probes were implanted in the substantia nigra reticulata (SNR) of rats. It was found that gamma-vinyl-GABA (1000 mg/kg) induced a 4-6-fold increase in the extracellular content of GABA. This increase lasted for at least 72 h. PTZ-induced convulsions were partly antagonized by the GVG treatment. The increase of extracellular GABA after gamma-vinyl-GABA was not affected by infusion of tetrodotoxin. In contrast valproic acid (200 mg/kg), although effective in preventing pentylenetetrazol (PTZ)-induced convulsions, did not affect extracellular GABA in the SNR. PTZ-induced convulsions did not modify extracellular GABA, neither in control rats nor in valproic acid or gamma-vinyl-GABA pretreated animals. The results do not support the idea that extracellular GABA in the SNR plays a significant role in anti-convulsive treatment. However, the present data can also be interpreted that extracellular GABA, as sampled by microdialysis, is not a reliable marker for GABA release.

Animals↗

PubMed1995

Brain microdialysis and its application for the study of animal behaviour.

Microdialysis is a sampling method that is used to determine the extracellular concentration of neurotransmitters in the brain. The method can be applied to conscious and unrestrained animals and is very suitable for the study of the chemistry of endogenous behaviour. This article reviews the contribution that microdialysis made to our understanding of the chemistry of behaviour. Methodological and practical considerations such as the implantation time and the use of guide cannulas are reviewed. The question whether neurotransmitters and related metabolites in dialysates reflect true synaptic release is critically discussed. There is much evidence that dopamine, noradrenaline, acetylcholine and serotonin in dialysates are related to neurotransmission, but there is serious doubt whether this is the case with amino acid transmitters such as GABA, glutamate and aspartate. Until now far over 100 papers appeared that used microdialysis in behavioural studies. Behavioural activation, the sleep-awake cycle and diurnal rhythms were subject of several of these studies. Various workers have described neurochemical changes in the brain that are related to feeding. Other studies were concerned with sexual behaviour and the sexual cycle in females. Parturition, maternal behaviour and offspring recognition have been studied in a series of microdialysis studies carried out in sheep. An overview is given of the microdialysis studies that were carried out to understand the biochemistry of stress. In this respect dopamine and noradrenaline have received much attention. A great number of microdialysis studies dealt with the role of dopamine in self-stimulation, reward and aversive emotions. It is concluded that microdialysis is at presently the most versatile and practical method to study the chemistry of behaviour and it is to be expected that it will soon be a routine methodology in behavioural research. Finally, perspectives and possible future developments of the methods are discussed.

Animals↗

PubMed1995

Semicircadian rhythm of dopamine release in the mediobasal hypothalamus in awake rats during pseudopregnancy: evidence that a thyrotropin-releasing hormone analogue stimulates dopamine release and thereby inhibits prolactin secretion.

The release of dopamine (DA) from tuberoinfundibular (TIDA) neurons during prolactin (PRL) surge and nonsurge periods and the effects of the thyrotropin-releasing hormone (TRH) analogue CG 3703 on DA and PRL secretion were studied in awake pseudopregnant (PSP) rats by simultaneous measurement of extracellular DA levels in the mediobasal hypothalamus (MBH) by means of microdialysis and of plasma PRL concentrations by radioimmunoassay of PRL in blood sampled from a permanent heart cannula. Since basal DA levels were low, the experiments were performed under local infusion of the reuptake inhibitor nomifensine (5 mumol/l), which increased extracellular DA levels 5-fold around the probe, but did not affect the occurrence of the nocturnal PRL surge on day 7-8 of PSP. Under nomifensine conditions, during the interphase (18.00-1.00 h) plasma PRL levels were low (< 50 ng/ml), while the DA release from TIDA neurons was elevated (approximately 250%) relative to the DA values measured during the phase when the nocturnal PRL surge occurred (100%; 1.00-12.00 h; plasma PRL levels were elevated to approximately 300 ng/ml). Thus, semicircadian rhythms were detected both for DA and PRL, which were broadly reciprocal in timing. The TRH analogue CG 3703 (100 and 500 micrograms/animal i.v.), when administered at 00.00 h, dose-dependently increased extracellular DA levels (to 300 and 500% of pretreatment values, respectively) and postponed the PRL surge in a corresponding manner (for approximately 2 and 3 h, respectively). Thus, in addition to its PRL-releasing effects, TRH can also suppress the PRL secretion by stimulating the release of DA from TIDA neurons, thereby increasing the inhibitor DAergic tone on lactotrophs. During the interphase, when DA levels were relatively elevated, administration of the DA blocking agent HA 966 (100 mg/kg body weight i.p.) at 20.00 h resulted in a short-lasting decrease in extracellular DA levels (to approximately 60% of pretreatment values for 30 min) accompanied by an immediate, short-lasting increase in PRL levels (to 400 ng/ml for approximately 1 h). Administration of CG 3703 (500 micrograms/animal i.v.) in combination with HA 966 (100 mg/kg body weight i.p.) at 20.00 h prevented the decrease in DA levels and the rise in plasma PRL values. Thus, the TRH analogue and HA 966 counteracted each other regarding the DAergic system, which again illustrates the stimulatory effect of the TRH analogue on the release of DA from TIDA neurons. Moreover, our results suggest that the interphase and the phase during which the nocturnal PRL surge occurs under the condition of PSP differ with regard to the DAergic inhibition of the PRL secretion; during the interphase the DAergic inhibitory tone prevents the rise in PRL secretion, while during the nocturnal PRL surge period another factor in addition to a decrease in DA levels appears necessary to increase plasma PRL levels.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Characterisation of the DA-ergic system in the mediobasal hypothalamus: a new approach to simultaneously monitor the release of DA from the TIDA neurons and the PRL secretion from the adenohypophysis in awake rats.

The TIDA neurons, which constitute part of the arcuate nucleus-ME complex, play an important inhibitory role in the regulation of the PRL secretion from the adenohypophysis. To simultaneously study the release of DA from the TIDA neurons and the PRL secretion from the adenohypophysis in awake rats, a microdialysis probe was implanted into the MBH together with a permanent heartcannula in male rats. The extracellular levels of DA in the MBH as measured by microdialysis decreased to 25% of basal values after local infusion of TTX (1 mumol/l), indicating that the released DA was directly derived from neuronal activity. DOPAC levels were not affected. This local infusion of TTX into the MBH induced parallel to the immediate decrease in DA levels, a profound increase in PRL concentration in the blood (from 10 to 55 ng/PRL-RP-2/ml) directly after infusion. Thus, the area in which the dialysis probe was inserted indeed included the DA-ergic neurons that regulate the PRL secretion. Evidence for a functional re-uptake system in the MBH was obtained by local infusion of the re-uptake inhibitor nomifensine (5 mumol/l) which induced an increase in DA release to 350% of basal values, without affecting the DOPAC levels. In spite of this increase in DA levels, the PRL concentration in the blood was not affected. In pseudopregnant female rats, relatively high levels of extracellular DA in the MBH were obtained during the interphase during which the PRL levels are low, while lower DA levels were apparent during the phase the spontaneous nocturnal PRL surge normally appears. Taken together, the approach presented in this study, i.e. the simultaneous measurements of DA in the MBH and PRL in the blood, establishes an advanced method enabling studies on the DA-PRL interactions in awake animals.

3,4-Dihydroxyphenylacetic Acid↗