Katsuhide Kariya

Median preoptic neurons projecting to the hypothalamic paraventricular nucleus are sensitive to blood pressure changes

Twenty-one neurons in the median preoptic nucleus (MnPO) were antidromically activated by electrical stimulation of the hypothalamic paraventricular nucleus (PVN) in male rats under urethane anesthesia. The activity of these identified neurons was tested for a response to activation of peripheral baroreceptors, achieved by rising arterial blood pressure with an intravenous administration of the alpha-agonist metaraminol. Of the neurons tested, 14 displayed a reduction and 2 exhibited an increase in neuronal excitability that accompanied a 30- to 50-mmHg elevation in mean arterial pressure, while 5 were unresponsive. The results show that efferent pathways from the MnPO to the PVN may receive neural inputs from the peripheral baroreceptors, suggesting the involvement of the pathways in the control of cardiovascular function.

Systemic administration of CCK-8S, but not CCK-4, enhances dopamine turnover in the posterior nucleus accumbens: a microdialysis study in freely moving rats

The present study was carried out to examine the effects of peripheral administration of sulfatedcholecystokinin octapeptide (CCK-8S) on dopamine (DA) turnover in the posterior nucleus accumbens (PNAc) and the caudate-putamen (CP) in awake rats. Microdialysis was used to quantify the extracellular concentrations of DA and its two metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Intraperitoneal injections of CCK-8S (0.3 mg/kg b.wt.) caused a significant increase in DOPAC and HVA concentrations in the PNAc, but did not affect the DA level. Such increases in the metabolite contents were not found in the CP. Similar injections of vehicle (1% NaHCO3 solution, 1 ml/kg b.wt.) did not have an effect in either brain region. In an attempt to determine the type of receptor involved in the CCK-8S-induced changes, CCK tetrapeptide (CCK-4, 0.3 mg/kg b.wt.) known to have high affinity for CCKB subtype or vehicle (10% DMSO-saline, 1 ml/kg b.wt.) was administered intraperitoneally. Neither CCK-4 nor vehicle caused significant changes in any of extracellular DA, DOPAC and HVA contents in the PNAc. These results suggest that peripherally administered CCK-8S has stimulatory effects on the dopaminergic system in the PNAc, and raise the possibility that the effect appears to be mediated via CCKA receptors.

Increased monoamine turnover in the subfornical organ area following body fluid depletion

To clarify whether monoaminergic inputs to the subfornical organ (SFO) area participate in fluid regulatory systems, we examined the effects of body fluid depletion on monoamine turnover in the region of the SFO using microdialysis techniques in rats. An iso-osmotic reduction of fluid volume following subcutaneous treatment with polyethylene glycol (PEG) significantly increased dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the SFO area. 5-hydroxytryptamine (5-HT) in the SFO area could be detected after the PEG treatment, while 5-HT was undetectable before the treatment. The data imply that both dopaminergic and serotonergic systems in the SFO area may be involved in controlling body fluid balance.

CCK activates excitatory ventral tegmental pathways to the posterior nucleus accumbens.

In urethane-anaesthetized male rats, electrical stimulation of the ventral tegmental area (VTA) produced either excitation (n = 26) or inhibition (n = 5) in the activity of neurones in the posterior nucleus accumbens (PNAc). Local administration of sulfatedcholecystokinin octapeptide (CCK8, 0.03 microgram) into the stimulation site enhanced the neuronal excitability in 10 out of 21 PNAc neurones that demonstrated the excitation to VTA stimulation, but did not affect the remaining 11 neurones. Similar administration, on the other hand, was without effect in any of PNAc neurones (n = 5) that displayed the inhibition to VTA stimulation. These results suggest that CCK8 may act at the VTA to elicit an activation of the excitatory pathways from the VTA to the PNAc.

Abnormal neural inputs from the median preoptic nucleus to the hypothalamic paraventricular nucleus in spontaneously hypertensive rats

554 ABNORMAL NEURAL INPUTS FROM THE MEDIAN PREOPTIC NUCLEUS TO THE HYPOTHALAMIC PARAVENTJUCULAR NUCLEUS IN SPONTANEOUSLY HYPERTENSIVE RATS JUNICHI TANAKA’, YASUSHI HAYASHI 2, KATSUHIDE KARIYA3, MASAHIKO NOMURA4 Depts. of ‘Human Dev. and 2Educ. for Handicapped Child., Naruto Univ. of Educ., Naruto, Tokushima 772-8502, 3Res. Lab., Torii & Co. Ltd., Midori-ku, Chiba 267-0056, 4Dept. of Physiol., Saitama Med. Sch., lruma-gun, Saitama, 350-0495 Extracellular single-unit activity was recorded from phasically firmg neurohypophyseal neurons tn the hypothalamic paraventricularnucleus (PVN) of male Wistar-Kyoto (WKY, 40 units) and spontaneously hypertensive rats (SHR, 38 units) under urethane anesthesia. Electrical stimulation of the median preoptic nucleus (MnPO) J)roduced orthodromic excitatton (48% in WKY rats; 51% in SHR) or inhibition (10% in WKY rats; 13% in SHR) of the activity of PVN units. No signifmant differences in the latency, duration or threshold of the MnPG stimulus-induced responses were observed between WKY and SHR. The magnitude of excitatory response, but not the inhtbitory response, much greater in SHR than m WKY rats. Local administration of angiotensin II (ANG II) into the stimulation sites enhanced the neuronal activity of units (64% in WKY rats; 67% in SHR) that displayed the excitation to electrical stimulation of the MnPO. The duration and frequency of excitatory response caused by the ANG II injection was much greater in SHR than in WKY rats. These results suggest that ANG IIsensitive MnPO efferents to the PVN act to facilitate the excitability of putative vasopressin-secreting neurons in the PVN and imply that there is the alteration between WKY and SHR in the functron of the pathways.

Ascending noradrenergic pathways from the nucleus of the solitary tract to the subfornical organ in rats

530 ASCENDING NORADRENERGIC PATHWAYS FROM THE NUCLEUS OF THE SOLITARY TRACT TO THE SUBFORNICAL ORGAN IN RATS KATSUHIDE KARIYAt, MASATERU KURUMIt, JUNICHI TANAKA2, YASUSHI HAYASH13, MASAHIKO NOMURA” tRes. Lab., Torii & Co. Ltd., Midori-ku, Chiba 267-0056, Depts. of 2Human Dev. and 3Educ. for Handicapped Child., Naruto Univ. of Educ., Naruto, Tokushima 772-8502, 3Dept. of Physiol.. Saitama Med. Sch., Iruma-gun, Saitama, 350-0495 The present study was carried out to clarify the role of noradrenergic pathways from the nucleus of the solitary tract (NTS) to the subfomical organ (SFO) in the cardiovascular function. In urethane-anesthetized male rats, electrical stimulation of the NTS produced orthodromic excitation (n=28, 15%) and inhibition (n=6,4%) of the activity of SF0 neurons. The excitation (n=26) was prevented by iontophoretically applied phentolamine (Phe), an a-adrencceptor antagonist, but not by timolol (Tim), a padrenoceptor antagonist. The inhibition (n=6) was not affected by either Phe or Tim. Approximately two-third (n=19) of SF0 neurons that exhibited the excitation to NT’S stimulation were also excited by hemorrhage (10 ml/kg). All the neurons that displayed the inhibition to NTS stimulation were not affected by hemorrhage. The effects of hemorrhage on extracellular noradrenaline (NA) concentrations in the SF0 region were examined using microdialysis techniques. Hemorrhage significantly increased the NA content in the SF0 region. These results imply that the noradrenergic NTS projections to the SF0 may carry the peripheral baroreceptor information that results in enhanced activity of SF0 neurons through a-adrenoceptor mechanisms.

612 Cholecystokininergic regulation of dopaminergic system in the rat posterior nucleus accumbens

The present study was carried out to clarify the action of cholecystokinin (CCK) on the dopaminergic system in the rat posterior nucleus accumbens (PNAc). The first experiment investigated the effects of microinjection of sulfated-CCK octapeptide (CCK-SS, 0.1 pg/kg) into the PNAc on dopamine (DA) turnover in the region of the injection site in awake rats. Microdialysis was utilized to quantify the extracellular concentrations of DA its major metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). CCK-8S injected into the PNAc caused an increase in DOPAC and HVA concentrations in the injection site, but did not affect the DA level. Similar injections of vehicle (1% NaHC03 solution, 0.1 rl/kg) did not have an effect. The second experiment examined the effects of microiontophoretic application of CCK-8S on the activity of PNAc neurons in rats treated with 6-hydroxydopamine (6-OHDA, 0.25 pg/kg) or vehicle (distilled water containing 0.2 mg/ml ascorbic acid, 0.5 ml/kg) in the poiterior part of PNAc, and intact rats under urethane anesthesia. The ratio of PNAc neurons that demonstrated an increased excitability in response to CCK-8S applied iontophoretically was markedly smaller in the 6-OHDA rats (11% and 5%: excitatory and inhibitory neurons) than in the vehicle (36% and 5%) and intact (34%,‘and 6%) rats. These results suggest that CCK acts at DA terminals in the PNAc to regulate the excitability of PNAc neurons.

617 Cholecystokininergic modulation of ventral tegmental dopaminergic inputs to the posterior nucleus accumbens in rats

Our previous study demonstrated that bradykinin increased intracellular free calcium concentration ( [Ca”ji) via bradykinin 82 receptors in primary cultured trigeminal ganglion cells of guinea pig. In this study, to investigate the correlation between bradykinin B2 receptors and prostaglandin E(PGE) receptor subtypes, we examined the effect of PGE2, 17-phenyl-trinor PGE2(EPt receptor agonist) and butaprost(EP2 receptor agonist) on the increase of [Ca2*ji induced by bradykinrn in cultured TG cells. PGE2(5fi M), 17phenyl-trinor PGE2 (0.1-10~ M) and butaprost (O.l-10~ M) did not give any change in [Ca2+]i, but markedly enhanced the bradykinin-Induced increase of [Ca’*ji. Among of those three, 17-phenyl-trinor PGE2was most potent. These results suggest that both EPt and EP2 receptors are involved in modulating the nociceptive information induced by bradykinrn in primary sensory neurons.