Chronic stress increases dopamine levels in hippocampal dentate gyrus and impairs spatial learning and memory in rats / 生理学报

The objective of this study was to elucidate the effect of chronic stress (CS) on dopamine (DA) level and synaptic efficiency in the hippocampal dentate gyrus (DG) during spatial learning and memory. Sprague Dawley (SD) male rats were randomly divided into control group and CS group (n = 10). CS group was treated with chronic mild unpredictable stress, and control group did not receive any treatments. The levels of epinephrine and corticosterone (CORT) in serum were measured by using enzyme-linked immunosorbent assay (ELISA); the spatial learning and memory abilities of rats were measured by Morris water maze (MWM) test. Meanwhile, the amplitude of field excitatory postsynaptic potential (fEPSP) and concentration of DA in the DG region were determined by in vivo electrophysiology, microdialysis and HPLC techniques during MWM test in rats. After that, the DA D1 receptor (D1R) and its key downstream members in DG were examined by immunohistochemistry or Western blot assay. The results showed that the levels of epinephrine and CORT in the serum of the rats in CS group were significantly increased compared with those in the control group (P < 0.05). In CS group rats, the escape latency was significantly prolonged and the number of platform crossing was markedly decreased during MWM test, compared with those in control group (P < 0.05). Furthermore, the amplitude of fEPSP in the DG was not changed during MWM test in CS rats, while it was significantly increased on the 3rd day of MWM test in control group (P < 0.05). Compared with baseline or control group, CS group showed significantly increased DA level from the 1st to 3rd days of MWM test in the DG (P < 0.05). In addition, the protein expression of D1R was markedly up-regulated in the DG in CS group, while the protein expression levels of p-PKA, p-CREB and BDNF were significantly reduced, compared with those in control group. These results suggest that CS may impair spatial learning and memory abilities in rats through the enhancement of the DA levels in the hippocampal DG.

Effect of 5-HT1A receptors in the hippocampal DG on active avoidance learning in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effects of serotonin (5-HTIA) receptors in the hippocampal dentate gyrus (DG) on active avoidance learning in rats.</p><p><b>METHODS</b>Totally 36 SD rats were randomly divided into control group, antagonist group and agonist group(n = 12). Active avoidance learning ability of rats was assessed by the shuttle box. The extracellular concentrations of 5-HT in the DG during active avoidance conditioned reflex were measured by microdialysis and high performance liquid chromatography (HPLC) techniques. Then the antagonist (WAY-100635) or agonist (8-OH-DPAT) of the 5-HT1A receptors were microinjected into the DG region, and the active avoidance learning was measured.</p><p><b>RESULTS</b>(1) During the active avoidance learning, the concentration of 5-HT in the hippocampal DG was significantly increased in the extinction but not establishment in the conditioned reflex, which reached 164.90% ± 26.07% (P <0.05) of basal level. (2) The microinjection of WAY-100635 (an antagonist of 5-HT1A receptor) into the DG did not significantly affect the active avoidance learning. (3) The microinjection of 8-OH-DPAT(an agonist of 5-HT1A receptor) into the DG significantly facilitated the establishment process and inhibited the extinction process during active avoidance conditioned reflex.</p><p><b>CONCLUSION</b>The data suggest that activation of 5-HT1A receptors in hipocampal DG may facilitate active avoidance learning and memory in rats.</p>

Changes of gamma-aminobutyric acid and glycine released in the medial vestibular nucleus following acute hypotension in conscious rats / 生理学报

To understand whether some amino acids in the medial vestibular nucleus (MVN) of conscious rats are involved in the regulation of blood pressure, microdialysis technique and high performance liquid chromatography (HPLC) were used to measure the changes of gamma-aminobutyric acid (GABA) and glycine (Gly) in this central area. Wistar rats (250-350 g) were randomly divided into three experimental groups: the control group with intact labyrinths; the ipsilateral MVN of unilateral labyrinthectomy (UL); contralateral MVN of the UL. Acute hypotension was induced by intravenous infusion of sodium nitroprusside (SNP). Unilateral chemical labyrinthectomy was performed 14 days before the start of the experiment to eliminate afferent signals from the peripheral vestibular receptors in the inner ear. Blood pressure decreased by 30% after SNP injection. In the control group, GABA and Gly release reduced to 43.53%+/-6.58% (P<0.01) and 62.24%+/-7.51% (P<0.01) respectively in the MVN following SNP-induced acute hypotension in conscious rats. In the contralateral MVN of UL, GABA and Gly release also reduced to 45.85%+/-17.27% (P<0.01) and 73.30%+/-3.00% (P<0.01) respectively following SNP-induced acute hypotension in conscious rats. In contrast, in the ipsilateral MVN of UL, GABA and Gly releases were not changed following SNP-induced acute hypotension in conscious rats. These results suggest that the SNP-induced acute hypotension may influence the activity of the neurons in the MVN by the afferent impulses from the peripheral vestibular organ, and that GABA and Gly may be involved in this process.

Cardiovascular change induced by central hypertonic saline are accompanied by GABA release in awake rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate the possible involvement of gamma-aminobutyric acid (GABA) in the paraventricular nucleus (PVN) in cardiovascular responses induced by central salt loading.</p><p><b>METHODS</b>Direct perfusion into PVN region with hypertonic saline (0.6 mol/L) was performed in conscious rats by using an in vivo brain microdialysis technique. Then, the extracellular concentration of GABA in the PVN region was measured by microdialysis and high performance liquid chromatography (HPLC) techniques, and the blood pressure (BP) and heart rate (HR) were with recorded simultaneously. Bicuculline (an antagonist of GABAA receptor) or saclofen (an antagonist of GABAB receptor) were coperfused hypertonic saline into PVN region, then the cardiovascular responses were examined.</p><p><b>RESULTS</b>(1) The local perfusion of 0.6 mol/L saline elicited significant increases on BP and HR (P < 0.01). In addition, perfusion of 0.6 mol/L saline increased the extracellular GABA levels in the PVN region, which reached 561.96% +/- 173.96% (P < 0.05) of the basal level. (2) Bicuculline or salcofen significantly attenuated the in-response of BP (P < 0.01, respectively), whereas the antagonists did not influence the response of HR induced by hypertonic saline.</p><p><b>CONCLUSION</b>Local perfusion of hypertonic saline in the PVN region elicits a local release of GABA, which may act via GABA(A) and GABA(B) receptors to produce pressor response.</p>

Facilitative effect of glycine on regulation of baroreflex in the hypothalamic paraventricular nucleus of conscious rats / 生理学报

The hypothalamic paraventricular nucleus (PVN) is a central site for integration of the endocrine system and the autonomic nervous system. Despite a number of studies have pointed out the importance of the PVN in the central regulation of cardiovascular functions, the chemical mediators in the PVN responsible for mediating baroreflex are not well understood. In the present study, we used the conscious rats to investigate the possible involvement of glycine (Gly) in PVN in the central regulation of baroreflex induced by intravenous injection of phenylephrine (0.8 mug/0.04 mL, in 3 min). Then, the microdialysis sampling was performed in the PVN and the concentration of Gly in the microdialysate was measured by high performance liquid chromatography (HPLC) combined with electrochemical techniques, and mean arterial pressure (MAP) and heart rate (HR) were recorded simultaneously. Injection of phenylephrine elicited a significant increase (P<0.01) in MAP from the baseline of (99.5+/-14.2) mmHg to the maximum of (149.8+/-19.5) mmHg and a decrease (P<0.01) in HR from the baseline of (400.8+/-33.1) beats/min to the minimum of (273.4+/-40.8) beats/min, respectively. Synchronously, the injection of phenylephrine increased the level of Gly in the microdialysate from the PVN to (162.9+/-27.3)% of the basal level (P<0.05). Perfusion of strychnine (100 mumol/L), an antagonist of Gly receptor, into the PVN enhanced the pressor response and attenuated the bradycardic response during the baroreflex, resulting in a decrease in baroreflex sensitivity (P<0.001). Whereas, the perfusion of Gly (1 mmol/L) into the PVN did not affect the pressor response but enhanced the bradycardic response during the baroreflex, resulting in an increase in baroreflex sensitivity (P<0.001). These results suggest that endogenous Gly in the PVN may act via strychnine-sensitive Gly receptor to produce a facilitative effect on baroreflex.

Effect of antagonism of glutamate receptors in the PVN region on baroreflex in conscious rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate the possible involvement of glutamate(Glu) in the paraventricular nucleus (PVN) in the central regulation of baroreflex.</p><p><b>METHODS</b>The baroreflex was induced by intravenous injection of phenylephrine in conscious rats, and the extracellular concentration of Glu in the PVN region was measured by microdialysis and high performance liquid chromatography (HPLC) techniques. To determine whether the observed Glu release was involved in the baroreflex, NMDA and non-NMDA receptor antagonists, MK-801 and CNQX, were perfused in the PVN region during baroreflex.</p><p><b>RESULTS</b>During baroreflex, the Glu concentration in the PVN region immediately increased to 384.82% +/- 91.77% of basal level (P < 0.01). (2) During baroreflex, direct perfusion of MK-801 and CNQX in the PVN were attenuated the increase of blood pressure and enhanced the decrease of HR (P < 0.01),resulting a significant increase in baroreflex sensitivity (P < 0.01).</p><p><b>CONCLUSION</b>Glutamate in PVN is involved in central regulation of baroreflex, which may inhibit baroreflex via ionothopic glutamate receptors.</p>

Changes of amino acid concentrations in the rat medial vestibular nucleus following unilateral labyrinthectomy / 生理学报

To understand the neurochemical mechanisms underlying the vestibular compensation, we determined the levels of amino acids such as aspartate, glutamate, glutamine, glycine, taurine, alanine in the medial vestibular nucleus (MVN) following unilateral labyrinthectomy (UL), by using in vivo brain microdialysis and high-performance liquid chromatography technique. Rats were pretreated by infusing 2% lidocaine 1.2 mL or 10 mg arsanilic acid into the tympanic cavity to obstruct uni-periphery vestibular organ, and then the levels of amino acids were determined in MVN of normal control and ipsilateral or contralateral lesional (ipsi-/contra-lesional) rats. In the control experiment, the levels of aspartate, glutamate, glutamine, glycine, taurine, and alanine were (6.15 +/- 0.59), (18.13 +/- 1.21), (33.73 +/- 1.67), (9.26 +/- 0.65), (9.56 +/- 0.77) and (10.07 +/- 0.83) pmol/8 muL sample, respectively. The concentrations of aspartate and glutamate decreased, while the concentration of taurine increased in the ipsi-lesional MVN of rats 10 min after infusing 2% lidocaine into middle ear to obstruct uni-periphery vestibular organ. Whereas the concentration of glutamate increased, the concentrations of glycine and alanine decreased in the contra-lesional MVN, accompanied by imbalances of glutamate, glycine and alanine in the bilateral nuclei. In contrast, the levels of glutamate and alanine decreased, the level of glutamine increased in the ipsi-lesional MVN, and the level of glutamate decreased in the contra-lesional MVN of rats 2 weeks after infusing 10 mg arsanilic acid into the tympanic cavity to obstruct uni-periphery vestibular organ. Furthermore, the level of glutamine in the ipsi-lesional MVN was obviously higher than that in the contra-lesional MVN. These results demonstrate that an imbalance of different amino acids appeared in bilateral MVN after UL, and this imbalance decreased after the development of vestibular compensation. Whereas the imbalance of glutamine release in bilateral nuclei appeared after vestibular compensation.

Changes of glutamate and taurine released in the medial vestibular nucleus following acute hypotension / 生理学报

In order to understand whether some special amino acids in the medial vestibular nucleus (MVN) of rats are involved in the regulation of blood pressure, we used microdialysis technique and high performance liquid chromatography (HPLC) to measure the changes of glutamate and taurine in this central area. Acute hypotension was induced by hemorrhage from the femoral artery. It was observed that the basal release of glutamate and taurine in the MVN was stable about 90 min after the beginning of microdialysis. The basal release of glutamate was (18.96 +/- 0.27) pmol/sample (8 mul), and that of taurine was (7.73 +/- 0.05) pmol/sample (8 mul). Glutamate release increased (P<0.05) and taurine release reduced (P<0.05) in the MVN in the hemorrhage-induced acute hypotensive rats. Nevertheless, these changes were not observed in the hemorrhage-induced acute hypotensive rats which were pretreated by infusing 2% lidocaine into the middle ear or 100 mg arsanilic acid into the tympanic cavity. These results suggest that the hemorrhage-induced acute hypotention can influence the activity of the neurons in the MVN by the afferent impulses from vestibular organ, and that some special amino acid transmitters in the MVN are involved in this process.

Effect of microinjection of atrial natriuretic peptide into the paraventricular nucleus on baroreflex sensitivity in conscious rats / 生理学报

The role of atrial natriuretic peptide (ANP) in the central regulation of the circulation is known to be a neurotransmitter or a neuromodulator, but its actions on baroreceptor reflex function are not fully resolved. The present study examined the role of ANP (6, 60 ng/0.2 microl) by direct microinjection into the hypothalamic paraventricular nucleus (PVN) in conscious rats. OPC-21268 (0.45 microg/3 microl), an antagonist of the V(1) receptor, was microinjected into the lateral ventricle to examine whether the effect of ANP on baroreflex sensitivity is mediated by vasopressin (VP). ANP significantly increased the baroreflex sensitivity, and OPC-21268 attenuated the increase of baroreflex sensitivity induced by ANP. Intravenous injections of ANP (60 ng/0.04 ml) did not affect baroreflex sensitivity. These results suggest that ANP in the PVN may produce a facilitative effect on baroreflex, and the effect may be via, at least in part, the central vasopressin.