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A Philippu

Publications and source records attributed to A Philippu.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effects of local MAO inhibition in the locus coeruleus on extracellular serotonin and 5-HIAA during exposure to sensory and cardiovascular stimuli.

Previously, we have shown that in the presence of pargyline the release of serotonin (5-HT) in the locus coeruleus is modulated by various sensory stimuli and blood pressure fluctuations. The aim of the present study was to investigate whether local inhibition of monoamine oxidase (MAO) influences basal and stimulus-induced release of 5-HT in the locus coeruleus. For this purpose, the locus coeruleus was superfused in the absence and in the presence of the MAO inhibitor pargyline. Additionally, we examined whether the release of the 5-HT metabolite 5-hydroxy-indole acetic acid (5-HIAA) in the locus coeruleus is altered in response to stimuli. The locus coeruleus of the conscious rat was superfused through a push-pull cannula with artificial cerebrospinal fluid (CSF). 5-HT and 5-HIAA were determined in the superfusate. The basal release rate of 5-HT and the basal outflow of 5-HIAA averaged 2.0 fmol/min and 69 fmol/min, respectively. The basal release rate of 5-HT and the 5-HIAA outflow were tetrodotoxin (TTX)-sensitive. In the absence of pargyline, the sensory stimuli noise stress or tail pinch, applied for 10 min, increased 5-HT and 5-HIAA outflow by 50-70%. In contrast, an experimentally induced rise in blood pressure for 10 min enhanced 5-HT release by 50%, but had no effect on 5-HIAA outflow. The release of 5-HT and/or 5-HIAA elicited by sensory stimuli or a blood pressure rise was abolished by TTX. Addition of pargyline to the CSF enhanced 5-HT release fourfold and slightly decreased 5-HIAA outflow. These levels remained stable throughout the entire observation period of 8 h. In the presence of pargyline, 5-HT release elicited by noise, tail pinch and increase in blood pressure was enhanced. It is concluded that superfusion with pargyline enhances 5-HT release and reduces 5-HIAA outflow in the locus coeruleus. Furthermore, the ability of sensory stimuli and baroreceptor activation to enhance 5-HT release is preserved during a prolonged pargyline-induced increase in extracellular 5-HT. Since sensory stimuli enhanced, while baroreceptor activation did not influence 5-HIAA outflow, 5-HIAA is not a reliable index for short-term changes in the activity of serotonergic neurons in the locus coeruleus.

Acoustic Stimulation↗
PubMed1999

Dependence of serotonin release in the locus coeruleus on dorsal raphe neuronal activity.

The serotonergic innervation of the locus coeruleus paetly derives from the dorsal raphe nucleus (DRN). Using the push-pull superfusion technique, we investigated whether and to what extent the release of serotonin and the extracellular concentration of its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the locus coeruleus are influenced by the neuronal activity of the DRN. In anaesthetized rats, a push-pull cannula was inserted into the locus coeruleus, which was continuously superfused with artificial cerebrospinal fluid (aCSF). Serotonin and 5-HIAA levels in the superfusate were determined by HPLC combined with electrochemical detection. Electrical stimulation (5 Hz, 300 microA, 1 ms) of the DRN for 5 min, or its chemical stimulation by microinjection of glutamate (3.5 nmol, 50 nl), led to an increased release of serotonin in the locus coeruleus and to a slight (2 mmHg) decrease in blood pressure. Superfusion of the locus coeruleus with tetrodotoxin (1 microM) abolished the increase in the release rate of serotonin evoked by electrical stimulation of the DRN, while the slight fall in blood pressure was not influenced. Thermic lesion (75 degrees C, 1 min) of the DRN elicited a pronounced decline in serotonin release rate within the locus coeruleus, the maximum decrease being 52%. The decrease in the release of serotonin was associated with a long-lasting rise in blood pressure. Microinjection of the serotonin neurotoxin 5,7-dihydroxytryptamine (5 microg, 250 nl) into the DRN led to an initial increase in the serotonin release rate that coincided with a short-lasting fall in blood pressure. Subsequently, the release of serotonin was permanently reduced and was associated with hypertension. Microinjection of the 5-HT1A receptor agonist (+/-)-8-hydroxy-dipropylaminotetralin (8-OH-DPAT; 7.5 nmol, 50 nl) into the DRN led to a long-lasting reduction of the release rate of serotonin in the locus coeruleus. Microinjection of 8-OH-DPAT into the DRN also slightly lowered blood pressure (3 mmHg). Neither stimulations nor lesion of the DRN, nor microinjection of 8-OH-DPAT into this raphe nucleus, altered the extracellular concentration of 5-HIAA. Judging from the present biochemical results it appears that the serotonergic afferents to the locus coeruleus originate to more than 50% from cell bodies located in the DRN. The neuronal serotonin release in the locus coeruleus is modulated by 5-HT1A receptors lying within the DRN. Changes in blood pressure and release of serotonin elicited by stimulating or lesioning the DRN point to the importance of serotonergic neurons extending between this raphe nucleus and the locus coeruleus in central cardiovascular control.

5,6-Dihydroxytryptamine↗
PubMed1999

Release of serotonin in the locus coeruleus of normotensive and spontaneously hypertensive rats (SHR).

The aim of the present work was to clarify whether differences exist between the release of endogenous serotonin in the locus coeruleus of normotensive and hypertensive rats. The locus coeruleus was superfused with artificial cerebrospinal fluid (aCSF) through a push-pull cannula and serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were determined in the superfusate by HPLC combined with electrochemical detection. Compared with normotensive Wistar-Kyoto (WKY) rats, the basal release rate of serotonin in the locus coeruleus of spontaneously hypertensive rats (SHR) was increased more than twofold. Intravenous infusion of noradrenaline (4 microg/kg min) increased mean arterial blood pressure to the same extent in hypertensive and normotensive rats. The pressor response was associated with an increased serotonin release. In WKY rats, the release of serotonin in the locus coeruleus evoked by noradrenaline infusion was more pronounced than in SHR. In WKY rats, intravenous infusion of sodium nitroprusside (150 microg/kg min) led to a fall in blood pressure which was less pronounced and lasted shorter than in SHR. The depressor response was associated with decreased serotonin release. In WKY rats, the decrease in serotonin release evoked by sodium nitroprusside was more pronounced and lasted longer than in SHR. Neither noradrenaline nor sodium nitroprusside influenced the outflow of 5-HIAA. The sensory stimuli noise and tail pinch led to a slight rise in arterial blood pressure which was similar in WKY rats and SHR. These stimuli enhanced the release rate of serotonin and the outflow of 5-HIAA to the same extent in the locus coeruleus of normotensive and hypertensive rats. The findings suggest that the enhanced release of serotonin in the locus coeruleus of genetically hypertensive rats reflects a mechanism counteracting the disturbed blood pressure homeostasis. Stressors influence blood pressure and release of serotonin in the locus coeruleus of SHR and WKY rats to the same extent.

Animals↗
PubMed1999

The release of catecholamines in hypothalamus and locus coeruleus is modulated by peripheral chemoreceptors.

To investigate whether impulses from chemoreceptors influence the release of catecholamines in the hypothalamus and the locus coeruleus, the two brain areas were superfused simultaneously and bilaterally with artificial cerebrospinal fluid through push-pull cannulae. The release of catecholamines was determined in the superfusate before and during chemoreceptor stimulation by bicarbonate solution saturated with carbon dioxide (CO2-NaHCO3) or KCN. Experiments were carried out on intact cats after carotid body denervation (CD). Intracarotid infusion of CO2-NaHCO3 increased arterial blood pressure and enhanced the release of noradrenaline but not dopamine in the posterior hypothalamus and the locus coeruleus. Following CD, the enhancing effect of CO2-NaHCO3 on the noradrenaline release in the posterior hypothalamus was abolished, while the effect on blood pressure was slightly enhanced. CD reversed the NaHCO3-induced release of noradrenaline in the locus coeruleus to a decreased noradrenaline outflow. Intracarotid infusion of KCN led to a fall in blood pressure. KCN increased the release rates of noradrenaline and, to a lesser extent, that of dopamine in the posterior hypothalamus, as well as the release of noradrenaline in the locus coeruleus. CD abolished the KCN-induced fall of blood pressure and the increased release of noradrenaline and dopamine in the posterior hypothalamus. Similar to CO2-NaHCO3, the enhancing effect of KCN on the noradrenaline release in the locus coeruleus was reversed following CD to a reduced noradrenaline outflow. Superfusion of the posterior hypothalamus and the locus coeruleus with KCN did not influence either blood pressure or the release rates of noradrenaline and dopamine in these brain areas. The findings show that impulses originating from chemoreceptors of the carotid body increase the release rates of the catecholamines in the posterior hypothalamus and the locus coeruleus, thus underlining the importance of catecholaminergic neurons of these brain areas in cardiovascular control.

Animals↗
PubMed1999

Histaminergic neurons modulate acetylcholine release in the ventral striatum: role of H3 histamine receptors.

To investigate whether histaminergic neurons influence the activity of cholinergic neurons, the ventral striatum was superfused through a push-pull cannula and the release of endogenous acetylcholine was determined in the superfusate. Local inhibition of histamine synthesis by superfusion with alpha-fluoromethylhistidine (FMH) gradually decreased the release rate of acetylcholine. Superfusion with histamine increased the release of acetylcholine. The releasing effect of histamine was greatly inhibited when the striatum was simultaneously superfused with the D2/D3 agonist quinpirole and the D1 antagonist (+/-)-7-bromo-1-(fluoresceinylthioureido)phenyl-8-hydroxy-3-methyl -2,3,4,5-tetrahydro-1H-3-benzapine (SKF 83566). The effect of histamine on acetylcholine release was abolished by the GABA(A) receptor antagonist bicuculline. Superfusion with the H3 receptor agonists imetit or immepip increased acetylcholine release rate in the striatum. The releasing effects of the two H3 agonists were FMH resistant, while superfusion with quinpirole and SKF 83566 abolished the H3 receptor agonist-induced acetylcholine release. Superfusion with the H3 receptor antagonist thioperamide enhanced acetylcholine release rate. The releasing effect of thioperamide was abolished after inhibition of histamine synthesis by FMH. The release of acetylcholine by thioperamide was also abolished on simultaneous superfusion with quinpirole and SKF 83566. The findings show that, in the striatum, the activity of cholinergic neurons is permanently modulated by neighbouring histaminergic nerve terminals and axons. The release of acetylcholine is also permanently inhibited by neighbouring GABAergic neurons. The enhanced release of acetylcholine by the H3 receptor agonists imetit and immepip is due to stimulation of H3 heteroreceptors, while the increase of acetylcholine release by the H3 receptor antagonist thioperamide is elicited via blockade of H3 autoreceptors. Histamine released from histaminergic nerve terminals increases the release of acetylcholine in part by inhibition of dopamine release which, in turn, decreases GABAergic transmission. A dopamine-independent way seems also to be involved in the histamine-evoked acetylcholine release.

Acetylcholine↗
PubMed1999

Histaminergic neurons modulate acetylcholine release in the ventral striatum: role of H1 and H2 histamine receptors.

To investigate whether H1 and H2 histamine receptors are implicated in the modulation of acetylcholine release by endogenous histamine, the ventral striatum of the conscious, freely moving rat was superfused by the push-pull superfusion technique with drugs and the release of acetylcholine was determined in the superfusate. Superfusion with the H1 receptor agonist 2-thiazolylethylamine (TEA, 50 micromol/l) enhanced the release of acetylcholine, while the H1 receptor antagonist triprolidine (50 micromol/l) reduced acetylcholine outflow and abolished the TEA-evoked release of the neurotransmitter. The inhibitory effect of triprolidine was not influenced either on simultaneous superfusion with 10 micromol/l (+/-)-7-bromo-1-(fluoresceinylthioureido)phenyl-8-hydroxy-3-methyl -2,3,4,5-tetrahydro-1H-benzazepine (SKF-83566, D1 dopamine receptor antagonist) and 50 micromol/l quinpirole (D2/D3 dopamine receptor agonist) or on superfusion with the GABAA receptor antagonist bicuculline (50 micromol/l). The H2 receptor antagonists ranitidine or famotidine (50 micromol/l each) greatly enhanced acetylcholine release rate in the ventral striatum. Presuperfusion with alpha-fluoromethylhistidine (FMH, 1 mmol/l), which inhibits neuronal synthesis of histamine, abolished the famotidine-induced release of acetylcholine. The releasing effect of famotidine was also abolished on simultaneous superfusion with 10 micromol/l SKF-83566 and 50 micromol/l quinpirole. The release of acetylcholine elicited by famotidine was reversed to a decreased acetylcholine outflow when the striatum was superfused with the GABA(A) receptor antagonist bicuculline (50 micromol/l) prior to famotidine. Superfusion with the H2 receptor agonist impromidine (1 micromol/l) decreased acetylcholine outflow, while the H2 agonist dimaprit (50 micromol/l) exerted the opposite effect. The releasing effect of dimaprit was not influenced by FMH (1 mmol/l), but it was abolished in the presence of SKF-83566 (10 micromol/l) and quinpirole (50 micromol/l). In the presence of bicuculline the release of acetylcholine by dimaprit was enhanced and prolonged. It seems possible that dimaprit and impromidine stimulate different subtypes of H2 receptors. The findings suggest that the release of acetylcholine in the striatum is modulated by neighbouring histaminergic neurons in a complex way. Stimulation of H1 histamine receptors, probably located on cholinergic neurons, enhances acetylcholine release. Stimulation by histamine of H2 receptors located on cholinergic or GABAergic neurons enhances the release of acetylcholine, while stimulation of H2 receptors located on dopaminergic neurons exerts the opposite effect.

Acetylcholine↗
PubMed1998

Melatonin facilitates short-term memory.

The olfactory social memory test, based on the recognition of a juvenile rat by a male adult rat, was used to investigate whether melatonin influences memory. Intracerebroventricular (i.c.v.) injection of 1.1 nmol melatonin shortened recognition time, while the melatonin ML1 receptor antagonist luzindole (1 nmol) exerted the opposite effect. The facilitating influence of melatonin was abolished in the presence of 0.5 nmol luzindole. The findings suggest that endogenous melatonin facilitates short-term memory.

Animals↗
PubMed1998

Glial cells participate in histamine inactivation in vivo.

The ability of glial cells to take up histamine in vitro suggests that these cells may be involved in histamine inactivation. This prompted us to study the possible interactions between neuronal and glial processes which determine the histamine concentration in the synaptic cleft. In vitro experiments showed that the glial metabolic toxin, fluoroacetate (20 and 40 mmol/l) depressed histamine uptake into cultured astroglial cells and dissociated hypothalamic cells of rats. For in vivo experiments, the push-pull superfusion technique was used. In anaesthetized rat, the anterior hypothalamic area was superfused through the push-pull cannula with artificial cerebrospinal fluid (aCSF) or with aCSF which contained fluoroacetate and the release of endogenous histamine was determined in the superfusate. Hypothalamic superfusion with fluoroacetate (20 mmol/l) led to a pronounced increase in extracellular histamine. The effect of fluoroacetate was inhibited by 5 micromol/l tetrodotoxin. Superfusion with Ca++-free, Mg++-rich (12 mmol/l) aCSF inhibited the basal release rate of histamine. Under these conditions, 20 mmol/l fluoroacetate did not modify the level of the amine in the superfusate. These data demonstrate that depression of glial function enhances the concentration of histamine in the extracellular space by slowing down the uptake of the amine into the glial cells. Thus, under in vivo conditions, glial cells are directly involved in the continuous removal of neuronal histamine from the synaptic cleft.

Animals↗
PubMed1998

Influence of catecholamine receptor agonists and antagonists on the ultradian rhythm of the EEG in the posterior hypothalamus.

The power of delta and theta frequency bands of the EEG in the posterior hypothalamus of the rat fluctuates according to an ultradian rhythm. To investigate, whether catecholamine receptor ligands influence the ultradian EEG rhythm, drugs were applied intracerebroventricularly into the lateral ventricle of anaesthetized rats. Injection of the alpha1-adrenoceptor agonist (+/-)-methoxamine (150 nmol) abolished, while 25 nmol of the compound prolonged the cycle duration of the rhythmic changes in the delta and theta frequency bands. Injected into the lateral ventricle, the alpha2-adrenoceptor agonists 6-ethyl-5,6,7,8-tetrahydro-4H-oxazol[4,5-d] azepin-2-amine (B-HT 933) or clonidine (150 nmol each) prolonged the duration of the cycles of both frequency bands. The beta1/2-receptor agonists (+/-)-orciprenaline (300 nmol) and (R)-(-)-isoprenaline (150 nmol) slowed down the cycle durations of both frequency bands. The beta1-receptor agonist (+/-)-xamoterol (300 nmol) also prolonged the cycle durations of the delta and theta frequency bands. The beta1-receptor antagonist (S)-(-)-atenolol was ineffective (150 and 300 nmol). The beta2-receptor agonist (+/-)-salbutamol (300 nmol) shortened the duration of the ultradian rhythm in the two frequency bands, while the beta2-receptor antagonist (+/-)-1-[2,3-(dihydro-7-methyl-1 H-inden-4-yl) oxy]-3-[(1-methylethyl)amino]-2-butanol (ICI 118,551) (300 nmol) exerted the opposite effect. On the other hand, the D1 receptor agonist (+/-)-1-phenyl-2,3,4,5-tetrahydro-1H)-3-benzazepine-7,8-diol (SKF 38393) and the D2 agonist (4aR,8aR)-(-)-quinpirole (150 nmol each) slowed down the frequency of the ultradian rhythm. The powers of alpha and beta frequency bands were not significantly influenced by the catecholamine receptor ligands used in this study. The findings suggest that, in the posterior hypothalamus, the ultradian rhythm of the delta and theta frequency bands are prolonged when beta1-receptors are stimulated and shortened on stimulation of beta2-adrenoceptors. Endogenous catecholamines released from their neurons seem to shorten the duration of the rhythmic fluctuations by stimulating beta2-receptors and to slow down the frequency of the cyclic fluctuations by stimulating alpha2-adrenoceptors. The ultradian rhythm is also slowed down on stimulation of D1 and D2 receptors by endogenous dopamine. Together with previous observations, the results indicate that the ultradian EEG rhythm is susceptible to modulatory mechanisms mediated by catecholaminergic neurons.

Activity Cycles↗
PubMed1998

Release of neurotransmitters in the locus coeruleus.

In the past 15 years the release of neurotransmitters and their metabolites in the locus coeruleus (LC) has been studied by using three approaches: microdialysis; push-pull superfusion; and voltammetry. These sophisticated techniques, which render it possible to follow the time course and magnitude of neurochemical changes in anaesthetized and conscious animals, have permitted great strides towards understanding neurotransmission in the LC. It appears that noradrenaline, known to be released in distant terminal fields, is also released in the somatodendritic area of LC neurons in response to drugs and physiological stimuli. Furthermore, determination of in vivo release enables the identification of functionally important neurotransmitter systems involved in relaying and integrating information reaching the LC via afferent neurons. As outlined in this review, the release rates of glutamate, aspartate, gamma-aminobutyric acid, glycine, 5-hydroxytryptamine and catecholamines, are modified in particular by arousing and stressful stimuli, pain, changes in cardiovascular homeostasis, as well as during opioid withdrawal or the sleep-wake-cycle. Profound interactions also occur between some of the neurotransmitters released during these situations. It appears that individual stimuli produce distinct neurochemical changes which contribute to the regulation of neuronal LC activity. Stimuli that activate LC neurons, such as pain, fall of blood pressure, noise, opiate withdrawal, do not produce a uniform response but modality-specific release patterns of excitatory and inhibitory neurotransmitters within the LC. From these studies and from existing neuroanatomical and electrophysiological data our knowledge of how neurotransmitters work in concert to regulate the functional state of LC noradrenergic perikarya in physiological and pathophysiological conditions is just emerging.

Animals↗
PubMed1998

Influence of excitatory amino acids on basal and sensory stimuli-induced release of 5-HT in the locus coeruleus.

1. The interactions between 5-hydroxytryptaminergic neurones and excitatory amino acid utilizing neurones were studied in the locus coeruleus of conscious, freely moving rats. The locus coeruleus was superfused with artificial cerebrospinal fluid through a push-pull cannula and 5-hydroxytryptamine (5-HT) was determined in the superfusate that was continuously collected in time periods of 10 min. 2. Superfusion of the locus coeruleus with the NMDA receptor antagonist AP5 (10 microM), kynurenic acid (1 mM), or the AMPA/kainate receptor antagonist DNQX (10 microM) reduced the 5-HT release in the locus coeruleus. 3. Superfusion with the agonists NMDA (50 microM), kainic acid (50 microM) or AMPA (10 microM) enhanced the release rate of 5-HT. AP5 (10 microM) blocked the stimulant effect of NMDA, while tetrodotoxin (1 microM) failed to influence the NMDA-induced release of 5-HT. In the presence of 10 microM DNQX, the releasing effect of 50 microM kainic acid was abolished. 4. Pain elicited by tail pinch, as well as noise-induced stress, increased the release of 5-HT. Superfusion of the locus coeruleus with 10 microM AP5 reduced the tail pinch-induced 5-HT release. AP5 (10 microM) did not affect the noise-induced release of 5-HT which was reduced, when the locus coeruleus was superfused simultaneously with this concentration of AP5 and 1 microM kynurenic acid. DNQX (10 mM) failed to influence the release of 5-HT induced by tail pinch or noise. 5. The findings suggest that 5-hydroxytryptaminergic neurones of the locus coeruleus are tonically modulated by excitatory amino acids via NMDA and AMPA/kainate receptors. The release of 5-HT elicited by tail pinch and noise is mediated to a considerable extent through endogenous excitatory amino acids acting on NMDA receptors, while AMPA/kainate receptors are not involved in this process.

Acoustic Stimulation↗
PubMed1998

Nitric oxide-induced release of acetylcholine in the nucleus accumbens: role of cyclic GMP, glutamate, and GABA.

We have previously shown that the basal acetylcholine release in the ventral striatum is under the enhancing influence of endogenous nitric oxide (NO) and that NO donors cause pronounced increases in the acetylcholine release rate. To investigate the role of cyclic GMP, glutamate, and GABA in the NO-induced acetylcholine release, we superfused the nucleus accumbens, (Nac) of the anesthetized rat with various compounds through a push-pull cannula and determined the neurotransmitter released in the perfusate. Superfusion of the Nac with the NO donors diethylamine/NO (DEANO; 100 micromol/L), S-nitroso-N-acetylpenicillamine (SNAP; 200 micromol/L), or 3-morpholinosydnonimine (SIN-1; 200 micromol/L) enhanced the acetylcholine release rate. The guanylyl cyclase inhibitor 1H-(1,2,4)-oxodiazolo(4,3-a)quinoxalin-1-one (ODQ; 10 micromol/L) abolished the effects of DEANO and SIN-1. 6-(Phenylamino)-5,8-quinolinedione (LY-83583; 100 micromol/L), which also inhibits cyclic GMP synthesis, inhibited the releasing effects of DEANO and of SNAP, whereas the effect of SIN-1 on acetylcholine release was not influenced. The DEANO-induced release of acetylcholine was also abolished in the presence of 20 micromol/L 6,6-dinitroquinoxaline-2,3-dione (DNQX) and 10 micromol/L (+/-)-2-amino-5-phosphonopentanoic acid (AP-5). Simultaneous superfusion with 50 micromol/L quinpirole and 10 micromol/L 7-bromo-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF 83566) was ineffective. Superfusion with 500 micromol/L DEANO decreased the release of acetylcholine. The inhibitory effect of 500 micromol/L DEANO was reversed to an enhanced release on superfusion with 20 micromol/L bicuculline. Bicuculline also enhanced the basal release rate. These findings indicate that cyclic GMP mediates the NO-induced release of acetylcholine by enhancing the outflow of glutamate. Dopamine is not involved in this process. Only high concentrations of NO increase the output of GABA, which in turn decreases acetylcholine release. Our results suggest that cells that are able to release glutamate, such as glutamatergic neurons, are the main target of NO in the Nac.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1997

The release of inhibitory amino acids in the hypothalamus is tonically modified by impulses from aortic baroreceptors as a consequence of blood pressure fluctuations.

We investigated in conscious, freely moving rats whether the release of GABA, taurine and arginine in the hypothalamus is influenced by impulses originating from peripheral baroreceptors. The posterior hypothalamic nucleus was superfused with artificial cerebrospinal fluid through a push-push cannula and the release of amino acids was determined in the hypothalamic superfusate of control rats, as well as of rats after bilateral aortic denervation (AD). AD led to hypertension and increased the lability of arterial pressure. In sham-operated rats, intravenous infusion of phenylephrine increased blood pressure and the hypothalamic release of GABA and taurine. AD almost abolished the phenylephrine-induced release of the inhibitory amino acids. Similarly, the pressor response to hypervolaemia, elicited by blood injection, enhanced the release rates of GABA and taurine only in sham-operated rats. Baroreceptor unloading evoked either by intravenous infusion of nitroprusside, or by haemorrhage, decreased the release rates of GABA and taurine in sham-operated rats but not in AD rats. Electrical stimulation of the afferent aortic depressor nerve enhanced extracellular GABA and taurine in the posterior hypothalamic nucleus. The release rate of arginine was not influenced by alterations in baroreceptor activity either in sham-operated or in AD rats. The findings support the idea that, in the hypothalamus, GABA and taurine are involved in central blood pressure regulation. The release of these two amino acids seems to be driven tonically by baroreceptor impulses. Moreover, the findings indicate that the baroreceptors of the aortic arch play a crucial role in the mediation of changes in hypothalamic GABA and taurine outflow so as to counteract blood pressure fluctuations.

Amino Acids↗
PubMed1997

The ultradian EEG rhythm coincides temporally with the ultradian rhythm of histamine release in the posterior hypothalamus.

In the posterior hypothalamus of the rat, EEG power and release rates of several neurotransmitters oscillate according to ultradian rhythms. To investigate whether a causal relationship exists between EEG power and histamine release, the posterior hypothalamic area of the anaesthetized rat was superfused through a push-pull cannula combined with a tungsten electrode. Simultaneous EEG recording and determination of histamine release revealed that ultradian rhythms in the delta and theta frequency bands are negatively correlated to the release rate of histamine; periods of high neuronal activity, which might reflect synchronization of firing, coincide temporally with low release rate of histamine, while periods of low neuronal activity coincide with high histamine release rate. The alpha and beta frequency bands did not correlate with histamine release. The ultradian rhythm of EEG power and histamine release might be of importance for regulatory mechanisms, such as the secretion of hormones.

Activity Cycles↗
PubMed1997

Release of serotonin in the rat locus coeruleus: effects of cardiovascular, stressful and noxious stimuli.

To investigate the function of serotonergic neurons within the locus coeruleus, this brain nucleus of conscious, freely moving rats was superfused with artificial cerebrospinal fluid through a push-pull cannula and the extracellular concentration of serotonin was determined in the superfusate. Serotonin release was increased by depolarization with veratridine (5 microM) or 80 mM K+, while superfusion with tetrodotoxin (1 microM) or systemic administration of 8-hydroxy-2-(di-n-propylamino)tetralin substantially diminished the release rate of serotonin in the locus coeruleus. The pressor response to intravenous infusion of noradrenaline (4 micrograms/kg/min) was associated with a pronounced increase in the release rate of serotonin. Superfusion of the locus coeruleus with tetrodotoxin (1 microM) abolished the increase in serotonin release evoked by the pressor response. A fall of blood pressure produced by intravenous administration of nitroprusside (150 micrograms/kg/min) or chlorisondamine (3 mg/kg) diminished the release rate of serotonin. Immobilization, noise (95 dB) or tail pinch increased the release of serotonin in the locus coeruleus and slightly elevated blood pressure. Chlorisondamine abolished the rise in blood pressure elicited by tail pinch without influencing the increased serotonin release. Tail pinch-induced serotonin release was abolished by superfusion with tetrodotoxin. The findings demonstrate that neuronal serotonin release in the locus coeruleus responds to cardiovascular and sensory stimuli, suggesting a function of serotonergic neurons in central blood pressure regulation, as well as in the modulation of locus coeruleus activity by stress and noxious stimuli.

8-Hydroxy-2-(di-n-propylamino)tetralin↗