Kinji Yagi

Changes in firing rates of single preoptic and hypothalamic units following an intravenous administration of estrogen in the castrated female rat

Summary The firing rates of some units in preoptic and hypothalamic areas decreased after an estrogen injection, and were not restored within the observation period ranging up to 150 min. Some other units responded to estrogen with a transitory increase in firing rates, and the remaining units were unresponsive. The mean latency of responses was between 15 and 16 min and the mean duration (increase in firing rates) was between 23 and 32 min in each nucleus. Mean firing rates during the period before estrogen injection were lower in the units that were excited by estrogen than in the units that were inhibited by the hormone. The relationship between the mean interspike interval and the standard deviation was linear. An intravenous infusion of Lockes solution did not affect the electrical activity level. Differential responses after an estrogen injection were observed in simultaneous recordings of two units. Four of 12 units examined did not respond to a glucocorticoid but to estrogen. Units that were excited by estrogen responded repeatedly to the hormone administered successively. It is concluded that two types of estrogen responsive neurons that are either excited or inhibited by the hormone reside in the preoptic and hypothalamic areas of the female rat, and that neurons that are excited by estrogen probably adapt slowly. Physiological significance of these neurons was discussed in relation to the effects of plasma estrogen on the hypothalamic control of gonadotrophin secretion.

Role of noradrenergic projections to the bed nucleus of the stria terminalis in neuroendocrine and behavioral responses to fear-related stimuli in rats

The bed nucleus of the stria terminalis (BNST) receives dense noradrenergic projections from the brainstem and has been claimed to play a role in expression of a variety of stress responses. Fear-related stimuli suppress vasopressin and facilitate oxytocin release from the neurohypophysis and induce behavioral suppression. Here we investigated in male rats whether conditioned fear stimuli increase noradrenergic activity in the BNST and whether depletion of epinephrine content in the BNST prevents neuroendocrine and behavioral responses to fear stimuli. Environmental stimuli previously paired with electric footshocks increased the ratio of 3-methoxy-4-hydroxyphenylglycol to norepinephrine contents in the BNST, suggesting that the stimuli activated noradrenergic projections to the BNST. 5-Amino-2, 4-dihydroxy-alpha-methylphenylethylamine, a neurotoxin relatively selective for noradrenergic fibers, when injected into the BNST 7 days before measurement, decreased the content of norepinephrine by 95% and that of dopamine or serotonin by about 50%. In the rats that received the neurotoxin, the suppressive vasopressin but not the augmentative oxytocin response to intermittent footshocks was abolished. In the experiments with conditioned fear stimuli, the neurotoxin given before training partially but significantly impaired the suppressive vasopressin and behavioral responses to testing stimuli. The neurotoxin given after training, however, did not prevent the vasopressin, oxytocin or behavioral responses. The results suggest that noradrenergic fibers in the BNST mediate the suppressive vasopressin but not the augmentative oxytocin response to nonassociatively applied fear stimuli and that they modulate, in a facilitative fashion, acquisition but not retention or recall of the emotional memory associated with the vasopressin and behavioral responses to conditioned fear stimuli.

Electrophysiological identification of cell bodies of the tubero-infundibular neurones in the rat

1. Electrical stimulation of the median eminence induced unit responses in the suprachiasmatic, the ventromedial and the arcuate nuclei of the hypothalamus in the female rat anaesthetized with urethane.

Vasopressin Regulation of Noradrenaline Release Within the Supraoptic Nucleus

The effect of electrically evoked dendritic vasopressin release on noradrenaline release into the hypothalamic supraoptic nucleus was assessed by in vivo microdialysis in conjunction with high pressure liquid chromatography and electrochemical detection. Electrical activation of magnocellular supraoptic neurones by stimulation of their axons at the level of the neural lobe significantly increased noradrenaline release into the nucleus (2.5‐fold, P<0.03). This increase was completely blocked by administration of a nonpeptide vasopressin V1a receptor antagonist via the microdialysis probe. These data suggest that dendritically released vasopressin facilitates noradrenaline release into the hypothalamic nucleus.

Role of NMDA receptors in the emotional memory associated with neuroendocrine responses to conditioned fear stimuli in the rat.

Behavioral experiments have shown that the N-methyl D-aspartate (NMDA) subclass of glutamate receptor plays an important role in acquisition of emotional memory. Exposure of a rat to conditioned fear stimuli suppresses vasopressin (VP) release and augments oxytocin (OT) or prolactin (PRL) release from the pituitary. Present experiments aimed at investigating the effect of intraperitonially administered MK-801, an antagonist of NMDA receptor on the emotional memory associated with the suppressive VP and the augmentative OT or PRL responses to conditioned fear stimuli in male rats. MK-801 injected 30 min before training impaired the VP, OT and PRL responses to the testing fear stimuli. The antagonist injected after training, however, did not block the responses. MK-801 administered before testing impaired the previously acquired VP, OT and PRL responses to conditioned fear stimuli. In the experiments with non-associatively applied fear stimuli, MK-801 did not block the VP, OT or PRL response. In the experiments with novel environmental stimuli, MK-801 did not impair VP, OT or PRL responses. The results suggest that an activation of NMDA receptors are required to acquire and recall but not to consolidate or retain the emotional memory associated with VP, OT and PRL responses to conditioned fear stimuli.

Effects of suramin on neuroendocrine and behavioural responses to conditioned fear stimuli.

Conditioned fear stimuli suppress motor activity. The fear stimuli suppress vasopressin and facilitate oxytocin and prolactin release. These fear responses are impaired by selective destruction of noradrenergic neurones. Adenosine 5′-triphosphate is co-released from noradrenergic nerve terminals with noradrenaline. Thus the possibility arises that the behavioural and neuroendocrine responses may be mediated by purinergic rather than noradrenergic synapses. We examined whether suramin, an inhibitor of P2 and NMDA receptors, blocks conditioned fear responses. Suramin injected i.c.v. 30 min before testing stimuli impaired conditioned fear responses. The role of purinergic P2 receptors in expression of the behavioural and neuroendocrine responses to conditioned fear stimuli is discussed.

Endogenous calcitonin gene-related peptide modulates tachycardiac but not bradycardiac baroreflex in rats

Effects of intracisternally administered human calcitonin gene-related peptide (8-37) [hCGRP-(8-37)], an antagonist, and hCGRP, an agonist of the CGRP receptor in the rat central nervous system, on baroreflex sensitivity (BRS) were studied in conscious male rats. Each rat sequentially received intracisternally injected 0.9% saline and then hCGRP-(8-37) at doses of 1, 2.5, and 5 nmol in a volume of 10 μl at an interval of 15 min. Five minutes after each injection, sodium nitroprusside (SNP, 10 μg/kg) or phenylephrine hydrochloride (PE, 2 μg/kg) was intravenously administered to induce reflex tachycardia or bradycardia, respectively. Intracisternally administered hCGRP-(8-37) increased BRS of the reflex tachycardia induced by SNP in a dose-related manner but did not change the BRS after PE. Intracisternally injected hCGRP significantly decreased the BRS after SNP. The lowering effect of hCGRP on BRS after SNP was inhibited by hCGRP-(8-37) injected before hCGRP. These results suggest that endogenous CGRP in the lower brain stem is selectively involved in the tachycardiac but not the bradycardiac baroreflex and modulates the baroreflex in an inhibitory rather than facilitatory fashion.Effects of intracisternally administered human calcitonin gene-related peptide (8-37) [hCGRP-(8-37)], an antagonist, and hCGRP, an agonist of the CGRP receptor in the rat central nervous system, on baroreflex sensitivity (BRS) were studied in conscious male rats. Each rat sequentially received intracisternally injected 0.9% saline and then hCGRP-(8-37) at doses of 1, 2.5, and 5 nmol in a volume of 10 microliters at an interval of 15 min. Five minutes after each injection, sodium nitroprusside (SNP, 10 micrograms/kg) or phenylephrine hydrochloride (PE, 2 micrograms/kg) was intravenously administered to induce reflex tachycardia or bradycardia, respectively. Intracisternally administered hCGRP-(8-37) increased BRS of the reflex tachycardia induced by SNP in a dose-related manner but did not change the BRS after PE. Intracisternally injected hCGRP significantly decreased the BRS after SNP. The lowering effect of hCGRP on BRS after SNP was inhibited by hCGRP-(8-37) injected before hCGRP. These results suggest that endogenous CGRP in the lower brain stem is selectively involved in the tachycardiac but not the bradycardiac baroreflex and modulates the baroreflex in an inhibitory rather than facilitatory fashion.

Oxytocin Release from the Neurohypophysis after the Taste Stimuli Previously Paired with Intravenous Cholecystokinin in Anaesthetized Rats

Intravenously administered cholecystokinin octapeptide (CCK) induces oxytocin release from the neurohypophysis in anaesthetised rats. Memory of conditioned taste aversion can be acquired under anaesthesia. The present experiments aimed at investigating whether taste stimuli previously paired with iv CCK evoke oxytocin release from the neurohypophysis in urethane‐anaesthetised male rats. Sucrose solution (0.75–2.0 M) paired with iv CCK or the vehicle was applied to the tongue. After 3u2003h, sucrose solution was applied again. The second sucrose slightly increased plasma oxytocin concentration in rats that had received the first sucrose solution paired with the vehicle. Plasma oxytocin concentration after the second sucrose application, however, was significantly higher in CCK‐injected than in vehicle‐injected rats. In rats that received CCK 1u2003h before the first sucrose application, a second sucrose application did not produce the oxytocin response. The magnitude of the oxytocin response to the second sucrose solution was increased in a manner related to CCK doses. In separate experiments, NaCl solution (0.75 M) paired with CCK or the vehicle was applied to the tongue. The second NaCl solution applied 3u2003h after the first one facilitated oxytocin release both in the rats that had received CCK or the vehicle. The increase in plasma oxytocin, however, was significantly larger in CCK than in vehicle‐injected rats. In rats that had received the first sucrose solution paired with CCK, a second sucrose solution evoked a significantly larger increase in plasma oxytocin concentrations than a testing NaCl solution did. In rats that had received NaCl solution paired with CCK, a testing sucrose solution did not significantly change plasma oxytocin concentrations. These data suggest that the taste stimulus previously paired with iv CCK induces oxytocin release from the neurohypophysis in urethane‐anaesthetised rats.

Does the pineal gland play a role in neuroendocrine fear responses

The pineal gland secretes melatonin under an influence of suprachiasmatic nucleus neurones. Pinealectomy or melatonin administration affects behavioural responses to novel stimuli. Fear or novel stimuli inhibit vasopressin (VP) and facilitate oxytocin (OT) or prolactin (PRL) release from the pituitary. Thus the suprachiasmatic nucleus-pineal gland system may modulate VP, OT and PRL responses to conditioned fear stimuli. In the present experiments with male rats, pinealectomy or melatonin administration did not significantly change VP, OT or PRL responses to conditioned fear stimuli. Electrolytic lesions of the suprachiasmatic nuclei impaired VP but not OT or PRL responses. The results show that the pineal gland is not involved in neuroendocrine responses to conditioned fear stimuli and suggest that the suprachiasmatic nucleus is necessary for the VP response to fear stimuli.

Facilitative modulation by NMDA receptors of vasopressin and oxytocin responses to osmotic stimuli in rats

It is reported that central angiotensin II (Ang II) and neurokinin B (NKB) induce anti-diuresis with increasing 111 plasma Arg-vasopressin (AVP) via AVP cells in the paraventricular hypothalamic nucleus (PVN). But there arc only few morphological studies concerning the relationship among these substances. Therefore, we paid attention to the PVN and the supraoptic nuclei (SON), known as a nuclei of producing AVP.to investigate location of Ang II receptor , NKB receptor and AVP immunohistochemically. Most of all AVP cells in the PVN and SON showed immunorcactivity to Ang II recl2ptor type1 and NK-3 receptor. These findings suggest that Ang II and NKB activate directly AVP cells in the PVN and SON via .4ng II receptor type1 and NK-3 receptor, and released AVP results in the control of the body fluid. The NK-3 receptor antiserum used in this experiment was kindly provided from Dr. James E. Krause (Neurogcsn Corp.).