ABSTRACT
Microdialysis was employed to investigate whether N-methyl-d-asparatate (NMDA) glutamate receptor mechanisms are involved in the modulation of serotonin (5-hydoxytryptamine, 5-HT) release in the region of the lateral parabrachial nucleus (LPBN) in freely moving rats. Perfusion of NMDA (10 and 50 microM) through the microdialysis probe significantly enhanced extracellular concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the LPBN area. Local perfusion of the NMDA antagonist dizocilpine (MK801, 10 and 50 microM) did not change the basal 5-HT and 5-HIAA levels in the LPBN area. MK801 (10 microM) administered together with NMDA antagonized the stimulant effect of NMDA (10 microM). The intake of 0.3M NaCl and water induced by subcutaneous injections of the diuretic furosemide (FURO, 10 mg/kg) and the angiotensin converting enzyme inhibitor captopril (CAP, 5 mg/kg) produced significant increases in the 5-HT and 5-HIAA concentrations in the LPBN area. The increased levels of 5-HT and 5-HIAA caused by the combined treatment with FURO and CAP were attenuated by perfusion of MK801 (10 microM). These results indicate the participation of NMDA receptors in the control of 5-HT release in the LPBN area.
Subject(s)
Pons/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Serotonin/metabolism , Synaptic Transmission/physiology , Visceral Afferents/metabolism , Water-Electrolyte Balance/physiology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Diuretics/pharmacology , Drinking/drug effects , Drinking/physiology , Excitatory Amino Acid Agonists/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Extracellular Fluid/drug effects , Extracellular Fluid/metabolism , Glutamic Acid/metabolism , Hydroxyindoleacetic Acid/metabolism , Male , Microdialysis , Pons/drug effects , Presynaptic Terminals/drug effects , Presynaptic Terminals/metabolism , Rats , Rats, Wistar , Receptors, N-Methyl-D-Aspartate/drug effects , Sodium, Dietary/metabolism , Synaptic Transmission/drug effects , Thirst/drug effects , Thirst/physiology , Visceral Afferents/drug effects , Water-Electrolyte Balance/drug effectsABSTRACT
The present study was carried out to investigate whether 0.3 M NaCl and water intake alters the release of serotonin (5-hydoxytryptamine, 5-HT) in the region of the lateral parabrachial nucleus (LPBN) in freely moving rats. The ingestion of 0.3 M NaCl and water was induced by subcutaneous injections of the diuretic furosemide (FURO, 10 mg/kg) and the angiotensin converting enzyme inhibitor captopril (CAP, 5 mg/kg), and extracellular concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured using intracerebral microdialysis techniques. The intake of 0.3 M NaCl and water significantly enhanced the 5-HT and 5-HIAA levels in the LPBN area. The combined treatment with FURO and CAP elicited significant decreases in the 5-HT and 5-HIAA concentrations in the LPBN area under the condition that 0.3 M NaCl and water are not available for drinking. These results suggest that the serotonergic system in the LPBN area may play an important role in the modulation of sodium appetite and thirst.
Subject(s)
Drinking/physiology , Pons/metabolism , Serotonin/metabolism , Sodium/metabolism , Visceral Afferents/metabolism , Water-Electrolyte Balance/physiology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Down-Regulation/drug effects , Down-Regulation/physiology , Drinking/drug effects , Furosemide/pharmacology , Hydroxyindoleacetic Acid/metabolism , Male , Microdialysis , Pons/cytology , Pons/drug effects , Rats , Rats, Wistar , Sodium/pharmacology , Sodium Chloride/metabolism , Sodium Chloride/pharmacology , Visceral Afferents/cytology , Visceral Afferents/drug effects , Water-Electrolyte Balance/drug effectsABSTRACT
Previous observations have suggested that the noradrenergic system in the median preoptic nucleus (MnPO) is implicated in the regulation of body fluid balance and cardiovascular function. The present study was carried out to investigate whether water intake alters the release of noradrenaline (NA) in the MnPO area caused by hypovolemia in freely moving rats. Nonhypotensive hypovolemia was induced by subcutaneous polyethylene glycol (PEG), and extracellular levels of NA were measured using intracerebral microdialysis techniques. Subcutaneous injections of PEG (30%, 5 ml) significantly enhanced the NA release in the MnPO area. Water ingestion significantly attenuated the elevation in the NA release in the MnPO area induced by the PEG treatment. These results show the involvement of the noradrenergic system in the MnPO in the maintenance of body fluid volume, and suggest that the system may play an important role in the elicitation of hypovolemia-induced dipsogenic response.
Subject(s)
Drinking/physiology , Hypovolemia/metabolism , Norepinephrine/metabolism , Preoptic Area/metabolism , Animals , Excipients , Hypovolemia/chemically induced , Male , Microdialysis , Polyethylene Glycols , Preoptic Area/anatomy & histology , Preoptic Area/drug effects , Rats , Rats, Wistar , Time Factors , Water DeprivationABSTRACT
The present study was designed to examine whether noradrenergic projections from the A1 cell group in the ventrolateral medulla to the median preoptic nucleus (MnPO) transmit information from the peripheral baroreceptors. In urethane-anesthetized male rats, extracellular concentrations of noradrenaline (NA) in the region of the MnPO in response to hemorrhage (5 or 10 ml/kg) were monitored with in vivo microdialysis methods. Hemorrhage significantly increased the NA release in the MnPO area. The enhancement of NA release in the MnPO area caused by hemorrhage was significantly attenuated by previous injections of the local anesthetic lidocaine (2 %, 0.2 microl), but not by saline (0.2 microl), into the A1 region. These results suggest that the noradrenergic projections from the A1 region are important for carrying the peripheral baroreceptor information to the MnPO.
Subject(s)
Hemorrhage/metabolism , Norepinephrine/metabolism , Preoptic Area/metabolism , Anesthetics, Local/pharmacology , Animals , Blood/metabolism , Blood Pressure/drug effects , Disease Models, Animal , Dose-Response Relationship, Drug , Extracellular Space/metabolism , Hemorrhage/physiopathology , Lidocaine/pharmacology , Male , Microdialysis/methods , Preoptic Area/drug effects , Rats , Rats, Wistar , Sodium Chloride/pharmacologyABSTRACT
Microdialysis was employed to investigate whether gamma-aminobutyric acid (GABA) receptor mechanisms are involved in the regulation of noradrenaline (NA) release in the median preoptic nucleus (MnPO) in awake, freely moving rats. Perfusion with the GABA receptor antagonists as well as agonists was performed in the region of the MnPO through a microdialysis probe and dialysate levels of NA were measured. Perfusion with either bicuculline (10 and 50 microM), a GABA(A) receptor antagonist, or phaclofen (10 and 50 microM), a GABA(B) receptor antagonist, enhanced the release of NA in the MnPO area. Higher-dose perfusion with the GABA(A) agonist muscimol (50 microM) or the GABA(B) agonist baclofen (250 microM) decreased dialysate NA in the MnPO area. An iso-osmotic reduction of fluid volume following subcutaneous treatment with polyethylene glycol (PEG, 30%, 5 ml) significantly increased the NA level in the MnPO area. The increased levels of NA caused by the PEG treatment were attenuated by perfusion with muscimol (10 microM), but not by baclofen (50 microM). These results show the participation of both GABA(A) and GABA(B) receptors in the modulation of the release of NA in the MnPO area, and imply that the GABA(A) receptor mechanism may play an important role in the noradrenergic regulatory system of body fluid balance.
Subject(s)
GABA Agonists/pharmacology , GABA Antagonists/pharmacology , Norepinephrine/metabolism , Preoptic Area/metabolism , Receptors, GABA-A/metabolism , Receptors, GABA-B/metabolism , Animals , Male , Microdialysis , Preoptic Area/drug effects , Rats , Rats, WistarABSTRACT
The present study was carried out to investigate whether estrogen modulates the drinking response induced by activation of angiotensinergic neural pathways from the subfornical organ (SFO) to the median preoptic nucleus (MnPO). Microinjection of angiotensin II (ANG II, 10(-10) M, 0.2 microl) into the SFO elicited drinking in ovariectomized (OVX) female rats that were treated with either propylene glycol (PG) vehicle or estrogen benzoate (EB). The amount of water intake induced by the ANG II injection was significantly greater in the PG-treated than in the EB-treated animals. In both groups of female rats, previous injections of saralasin (Sar, 10(-10) M, 0.2 microl), a specific ANG II antagonist, into the MnPO resulted in the significant attenuation of the drinking response to ANG II, showing that the ANG II-induced drinking response may be mediated in part by the angiotensinergic SFO projections to the MnPO. Injections of ANG II (10(-10) M, 0.2 microl) into the MnPO caused drinking in both groups, while no significant difference was found between the groups in the amount of water intake. These results suggest that increases in the circulating level of estrogen may attenuate the drinking response induced by ANG II activation of the SFO projections to the MnPO.
Subject(s)
Angiotensin II/pharmacology , Drinking Behavior/drug effects , Estrogens/pharmacology , Neural Pathways/physiology , Preoptic Area/physiology , Subfornical Organ/physiology , Angiotensin II/administration & dosage , Angiotensin II/antagonists & inhibitors , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Drinking/drug effects , Drinking Behavior/physiology , Female , Microinjections , Neural Pathways/cytology , Neural Pathways/drug effects , Ovariectomy , Preoptic Area/cytology , Preoptic Area/drug effects , Propylene Glycol/pharmacology , Rats , Rats, Wistar , Saralasin/pharmacology , Subfornical Organ/cytology , Subfornical Organ/drug effectsABSTRACT
Previous findings have shown that some of the neurons in the median preoptic nucleus (MnPO) receive both catecholaminergic inputs from the brainstem and angiotensinergic inputs from the subfornical organ (SFO), and that alterations in the function of the brain renin-ANG system are implicated in hypertension, especially in spontaneous hypertensive rats (SHR). In an attempt to clarify the action of these inputs on MnPO neurons and to find the difference in the action between normotensive Wistar-Kyoto (WKY) rats and SHR, we used microdialysis to investigate the effects of injections of saralasin (Sar), an angiotensin II (ANG II) antagonist, into the third ventricle (3V) on monoamine release in the MnPO area of awake WKY and SHR. The content of noradrenaline (NA) in the MnPO area was significantly higher in SHR. No significant differences were observed between WKY and SHR in the concentrations of dopamine (DA) and of its two metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). In both WKY and SHR, Sar (Sar, 5 microg in 1 microl, three injections at 2-h intervals) injected into the 3V significantly decreased the extracellular concentrations of NA, DOPAC and HVA in the MnPO area. The decreases were much greater in SHR than in WKY rats. Similar injections of saline vehicle had no significant effect on the extracellular levels of NA, DA and the metabolites. These results suggest that central angiotensinergic circuits may serve to increase NA and DA release in the MnPO area, and support that a disorder in the ANG system may contribute, in part, to the elevated blood pressure of SHR.
Subject(s)
Angiotensin II/antagonists & inhibitors , Biogenic Monoamines/biosynthesis , Hypertension/physiopathology , Neural Pathways/drug effects , Neural Pathways/physiology , Preoptic Area/drug effects , Preoptic Area/physiology , Saralasin/pharmacology , Animals , Injections, Intraventricular , Male , Microdialysis , Neurons/drug effects , Preoptic Area/cytology , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Subfornical Organ/cytology , Subfornical Organ/drug effects , Subfornical Organ/physiologyABSTRACT
The present study was carried out to examine whether estrogen modulates the drinking response caused by activation of neural pathways from the subfornical organ (SFO) to the hypothalamic paraventricular nucleus (PVN) in the female rat. Microinjection of angiotensin II (ANG II) into the SFO elicited drinking in ovariectomized female rats that were treated with either propylene glycol (PG) vehicle or estradiol benzoate (EB). The amount of water intake induced by the ANG II injection was significantly greater in the PG-treated than in the EB-treated animals. In both groups, previous injections of either saralasin, an ANG II antagonist, or phentolamine, an alpha-adrenoceptor antagonist, bilaterally into the PVN resulted in the significant attenuation of the drinking response to ANG II, whereas similar injections of saline vehicle into the PVN were without effect. These results suggest that the circulating estrogen may act to reduce the drinking response that is mediated through angiotensinergic and alpha-adrenergic mechanisms in the PVN in response to angiotensinergic activation of SFO efferent projections.
Subject(s)
Angiotensins/metabolism , Drinking/physiology , Estrogens/metabolism , Neural Pathways/metabolism , Neurons/metabolism , Paraventricular Hypothalamic Nucleus/metabolism , Subfornical Organ/metabolism , Angiotensins/pharmacology , Animals , Antihypertensive Agents/pharmacology , Drinking/drug effects , Drug Interactions/physiology , Estrogens/pharmacology , Estrus/physiology , Female , Neural Inhibition/drug effects , Neural Inhibition/physiology , Neural Pathways/cytology , Neural Pathways/drug effects , Neurons/drug effects , Ovariectomy , Paraventricular Hypothalamic Nucleus/cytology , Paraventricular Hypothalamic Nucleus/drug effects , Phentolamine/pharmacology , Rats , Rats, Wistar , Reaction Time/drug effects , Reaction Time/physiology , Saralasin/pharmacology , Sodium Chloride/pharmacology , Subfornical Organ/cytology , Subfornical Organ/drug effectsABSTRACT
Thirty subfornical organ (SFO) neurons in normotensive Wistar-Kyoto (WKY) rats and 32 SFO neurons in spontaneously hypertensive rats (SHR) were antidromically activated by electrical stimulation of the hypothalamic paraventricular nucleus (PVN) under urethane anesthesia. The spontaneous firing rate was significantly higher in SHR than in WKY rats. No significant differences in the latency, conduction velocity, and threshold of antidromic response were observed between WKY and SHR. All the identified SFO units were tested for a response to intracarotid injection of angiotensin II (ANG II, 20-ng/kg b.w.t.). Injections of ANG II elicited an increase in the activity of 21 units in WKY and 20 units in SHR and a depression in the firing of one unit in WKY rats, but did not affect the remaining units. The magnitude of the excitatory response caused by the ANG II injection was much greater in SHR than in WKY rats. These results show that there are differences between WKY and SHR in the spontaneous discharge rate of SFO neurons projecting to the PVN and in their response to circulating ANG II.
