gamma-Aminobutyric acid (GABA), a major inhibitory neurotransmitter in the mammalian central nervous system, is involved in sleep physiology. Caffeine is widely used psychoactive substance known to induce wakefulness and insomnia to its consumers. This study was performed to examine whether GABA extracts from fermented rice germ ameliorates caffeine-induced sleep disturbance in mice, without affecting spontaneous locomotor activity and motor coordination. Indeed, caffeine (10 mg/kg, i.p.) delayed sleep onset and reduced sleep duration of mice. Conversely, rice germ ferment extracts-GABA treatment (10, 30, or 100 mg/kg, p.o.), especially at 100 mg/kg, normalized the sleep disturbance induced by caffeine. In locomotor tests, rice germ ferment extracts-GABA slightly but not significantly reduced the caffeine-induced increase in locomotor activity without affecting motor coordination. Additionally, rice germ ferment extracts-GABA per se did not affect the spontaneous locomotor activity and motor coordination of mice. In conclusion, rice germ ferment extracts-GABA supplementation can counter the sleep disturbance induced by caffeine, without affecting the general locomotor activities of mice.
Animals ; Anxiety ; Caffeine ; Central Nervous System ; gamma-Aminobutyric Acid* ; Mice* ; Motor Activity ; Neurotransmitter Agents ; Physiology ; Sleep Initiation and Maintenance Disorders ; Wakefulness

OBJECTIVE: We used electrophysiological methods to study that whether GABA could elicit OHCs outward currents provide evidence for exsitence of GABA-A receptor and investige the relationship between the effect of GABA and the development of OHCs. METHOD: We used whole-cell recording OHCs at current-clamp or voltage-clamp to verify the function of GABA receptor on OHCs. Then we counteds the responsive cells vs. total number cells, and according to results to study the relationships between the GABA receptor and development of OHCs. RESULT: OHC was elicited outward current or hyperpolarized by GABA and the responsive cells were decreased with development. CONCLUSION The result of GABA receptor decreasing with development suggested that the receptor may draw efferents to OHCs or facilitate the MOC-OHC synapse formation.
Animals ; Electrophysiological Phenomena ; Hair Cells, Auditory, Outer ; physiology ; Patch-Clamp Techniques ; Rats ; Receptors, GABA-A ; physiology ; gamma-Aminobutyric Acid ; physiology

OBJECTIVETo explore the modulatory effect of niflumic acid and blocker of calcium channel on the desensitization of gamma aminobutyric acid (GABA)-activated currents in dorsal root ganglion(DRG) neurons from rat.

METHODSThe whole-cell patch-clamp technique was used to observe the modulatory effect of niflumic acid and blocker of calcium channel on the desensitization of GABA-activated currents in neurons freshly dissociated from rat DRG neurons.

RESULTSApplication of GABA (0.1-1 000 micromol/L) could induce concentration-dependent inward currents in some cells (212/223, 95.11%). GABA-(100 micromol/L) activated currents was (1.32 +/- 0.74) nA (n = 84). However, pre-application of niflumic acid (1-100 micromol/L) and nitrendipine (specific blocker of L-calcium channel)(0.1-30 micromol/L) could inhibit the GABA-activated inward current which was identified to be GABAA receptor-mediated current. The inhibitory effects of niflumic acid and nitrendipine were concentration-dependent. The suppression rate of 10 micromol/L niflumic acid and nitrendipine to GABA-activated currents were (31.60% +/- 4.87%) (n = 19) and (43.60% < or = 5.10%) (n = 5), respectively. The desensitization of GABA-activated currents had double exponential characteristic. Tau value was (14.68 +/- 5.11) s (n = 6) and (175.8 +/- 42.67) s (n = 6, r = 0.9647), respectively. Pre-application of niflumic acid (100 micromol/L) and nickel chloride (nonspecific blocker of L-calcium channel) (100 micromol/L) altered tau value of the desensitization of GABA-activated currents, tau value reduced for (4.64 +/- 2.21) s (n = 3), (43.70 +/- 14.34) s ( n = 3, r = 0.9548) and (4.64 +/- 2.21) s (n = 3), (43.70 +/- 14.34) s (n = 3, r = 0.9721).

CONCLUSIONPre-application of niflumic acid exerts a more strong inhibitory effect on the peak value of GABA-activated current, which possibly is through blocking the calcium-activated chloride ion channel to accelerate the desensitization of GABA-activated currents.

Animals ; Animals, Newborn ; Calcium Channel Blockers ; pharmacology ; Calcium Channels, L-Type ; drug effects ; Ganglia, Spinal ; drug effects ; physiology ; Membrane Potentials ; drug effects ; physiology ; Neurons ; drug effects ; physiology ; Niflumic Acid ; pharmacology ; Nitrendipine ; pharmacology ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; gamma-Aminobutyric Acid ; pharmacology

OBJECTIVETo explore the modulatory effect of niflumic acid (NFA) on gamma aminobutyric acid (GABA)-activated currents of dorsal root ganglion (DRG) neurons in rat.

METHODSThe whole-cell patch-clamp technique was used to record the NFA- and GABA-activated currents in neurons freshly dissociated from rat DRG neurons.

RESULTSApplication of NFA(0.1 - 100 micromol/L) could induce concentration-dependent outward currents in some cells (21/48,43.75%), and GABA (0.1 - 100 micromol/L) could induce concentration-dependent inward currents in some cells(150/159,94.32%). NFA-(100 micromol/L) and GABA-(100 micromol/L) activated currents were (0.27 +/- 0.06) nA (n = 12) and (1.29 +/- 0.72) nA (n = 53) respectively. However, pre-application of NFA (0.1 - 100 micromol/L) could inhibit the GABA-activated inward current which was identified to be GABAA receptor-mediated current. The inhibitory effects of NFA were concentration-dependent. NFA could not alter the EC50 (about 30 micromol/L) and inverse potential (about -10 mV) of GABA-activated current (P > 0.05).

CONCLUSIONPre-application of NFA exerts a more strong inhibitory effect on the peak value of GABA-activated current.

Animals ; Cell Separation ; Cells, Cultured ; Ganglia, Spinal ; drug effects ; physiology ; Neurons ; drug effects ; physiology ; Niflumic Acid ; pharmacology ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; gamma-Aminobutyric Acid ; metabolism

OBJECTIVE: To analyze the survival and the changes of proportions of Calbindin, Calretinin and Parvalbumin positive neurons in mouse hippocampal CA area at chronic stage of Pilocarpine-induced epilepsy. METHODS: Calbindin, Calretinin and Parvalbumin immunofluoresence staining were done 2 months after Pilocarpine-induced epilepsy in mice or saline injection. RESULTS: Two months after Pilocarine-induced epilepsy, the number of Calbindin, Calretinin and Parvalbumin positive neurons in the CA area decreased significantly compared with the control (P<0.01), especially the Calbindin positive neurons had a great drop and Pavalbumin positive neurons had a least drop. At the chronic stage of epilepsy, the proportion of Calbindin, Calretinin and Parvalbumin positive neurons in the CA area was changed. The content of Pavalbumin positive neurons increased whereas the content of Calbindin positive neurons decreased significantly compared with the control (P<0.01). CONCLUSION The changes of proportions of Calbindin, Calretinin and Parvalbumin positive neurons in the CA area of mouse hippocampus may be a factor in the ongoing epileptic activity at chronic stage of Pilocarpine-induced epilepsy.
Animals ; Calbindin 2 ; metabolism ; Calbindins ; metabolism ; Cell Survival ; physiology ; Chronic Disease ; Epilepsy ; chemically induced ; metabolism ; Hippocampus ; metabolism ; Male ; Mice ; Neurons ; metabolism ; Parvalbumins ; metabolism ; Pilocarpine ; gamma-Aminobutyric Acid ; metabolism

Histaminergic neurons solely originate from the tuberomammillary nucleus (TMN) in the posterior hypothalamus and send widespread projections to the whole brain. Experiments in rats show that histamine release in the central nervous system is positively correlated with wakefulness and the histamine released is 4 times higher during wake episodes than during sleep episodes. Endogeneous prostaglandin E2 and orexin activate histaminergic neurons in the TMN to release histamine and promote wakefulness. Conversely, prostaglandin D2 and adenosine inhibit histamine release by increasing GABA release in the TMN to induce sleep. This paper reviews the effects and mechanisms of action of the histaminergic system on sleep-wake regulation, and briefly discusses the possibility of developing novel sedative-hypnotics and wakefulness-promoting drugs related to the histaminergic system.
Adenosine ; physiology ; Animals ; Dinoprostone ; physiology ; Histamine ; metabolism ; physiology ; Hypothalamic Area, Lateral ; physiology ; Intracellular Signaling Peptides and Proteins ; physiology ; Neurons ; physiology ; Neuropeptides ; physiology ; Orexins ; Prostaglandin D2 ; physiology ; Sleep ; physiology ; Wakefulness ; physiology ; gamma-Aminobutyric Acid ; metabolism

The purpose of the present study is to observe the effect of electro-acupuncture (EA) stimulation on intracerebral neurotransmitters in a rat model of Parkinson's disease (PD), and explore the possible mechanism. We used 6-hydroxydopamine (6-OHDA) injection in medial forebrain bundle (MFB) in the right brain of Sprague Dawley (SD) rat to establish the parkinsonian rat model, and randomly divided the PD rats into model and 100 Hz EA stimulation groups (n =10 in each group). EA stimulation group received 4 courses of EA stimulation on Baihui (GV-20) and Dazhui (GV-14) acupuncture points. Moreover, ten rats were randomly selected as sham operation group, only receiving normal saline (NS) injection in MFB. Then apomorphine (APO)-induced rotational behavior in different groups was recorded, and the contents of &gamma;-aminobutyric acid (GABA) in the brain were analyzed with high pressure/performance liquid chromatography-electrochemical detection (HPLC-ECD). The results showed that model group exhibited abnormal rotational behavior with APO treatment, suggesting the successful establishment of PD model. Compared with sham operation group, model group showed increased GABA contents in cortex and striatum, as well as decreased GABA content in ventral midbrain, on the lesioned side. EA stimulation could effectively ameliorate the abnormal rotational behavior of PD rat. Compared with the model group, EA stimulation decreased the ratio of GABA content on the lesioned side to that on unlesioned side in the cortex, while increased the ratios in the striatum and cerebellum. However, there was no difference of the ratio in the ventral midbrain among three groups. These results suggest high-frequency EA stimulation significantly improves the abnormal behavior of PD rats, which may exert through enhancing the inhibitory effect of cerebellum-basal ganglia-cortical loop on motor center.
Acupuncture Therapy ; Animals ; Brain ; metabolism ; Electroacupuncture ; Male ; Motor Cortex ; physiology ; Oxidopamine ; Parkinson Disease, Secondary ; chemically induced ; metabolism ; therapy ; Rats ; Rats, Sprague-Dawley ; gamma-Aminobutyric Acid ; metabolism

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.
Acute Disease ; Animals ; Chromatography, High Pressure Liquid ; Ear, Inner ; physiology ; surgery ; Glycine ; metabolism ; Hypotension ; metabolism ; physiopathology ; Male ; Microdialysis ; Random Allocation ; Rats ; Rats, Wistar ; Vestibular Nuclei ; metabolism ; physiology ; gamma-Aminobutyric Acid ; metabolism

Animals ; Brain ; cytology ; Cerebrospinal Fluid ; physiology ; Formaldehyde ; administration & dosage ; toxicity ; Inflammation ; chemically induced ; physiopathology ; Male ; Neurons ; metabolism ; physiology ; Pain ; chemically induced ; physiopathology ; Pain Measurement ; methods ; Rats ; Rats, Sprague-Dawley ; gamma-Aminobutyric Acid ; metabolism

AIMTo investigate the possible involvement of gamma-aminobutyric acid (GABA) in the paraventricular nucleus (PVN) in cardiovascular responses induced by central salt loading.

METHODSDirect 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.

RESULTS(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.

CONCLUSIONLocal 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.

Animals ; Blood Pressure ; drug effects ; physiology ; Male ; Microdialysis ; methods ; Paraventricular Hypothalamic Nucleus ; metabolism ; physiology ; Pressoreceptors ; drug effects ; Rats ; Rats, Wistar ; Saline Solution, Hypertonic ; administration & dosage ; pharmacology ; gamma-Aminobutyric Acid ; metabolism