The echolocating big brown bats (Eptesicus fuscus) emit trains of frequency-modulated (FM) biosonar signals with duration, amplitude, repetition rate, and sweep structure changing systematically during interception of their prey. In the present study, the sound stimuli of temporally patterned pulse trains at three different pulse repetition rates (PRRs) were used to mimic the sounds received during search, approach, and terminal stages of echolocation. Electrophysiological method was adopted in recordings from the inferior colliculus (IC) of midbrain. By means of iontophoretic application of bicuculline, the effect of GABAergic inhibition on the intensity sensitivity of IC neurons responding to three different PRRs of 10, 30 and 90 pulses per second (pps) was examined. The rate-intensity functions (RIFs) were acquired. The dynamic range (DR) of RIFs was considered as a criterion of intensity sensitivity. Comparing the average DR of RIFs at different PRRs, we found that the intensity sensitivity of some neurons improved, but that of other neurons decayed when repetition rate of stimulus trains increased from 10 to 30 and 90 pps. During application of bicuculline, the number of impulses responding to the different pulse trains increased under all stimulating conditions, while the DR differences of RIFs at different PRRs were abolished. The results indicate that GABAergic inhibition was involved in modulating the intensity sensitivity of IC neurons responding to pulse trains at different PRRs. Before and during bicuculline application, the percentage of changes in responses was maximal in lower stimulus intensity near to the minimum threshold (MT), and decreased gradually with the increment of stimulus intensity. This observation suggests that GABAergic inhibition contributes more effectively to the intensity sensitivity of the IC neurons responding to pulse trains at lower sound level.
Acoustic Stimulation ; Animals ; Bicuculline ; pharmacology ; Chiroptera ; Echolocation ; Electrophysiological Phenomena ; GABA-A Receptor Antagonists ; pharmacology ; Inferior Colliculi ; cytology ; Neurons ; cytology

In the present study, the correlated activities of adjacent ganglion cells of transient subtype in response to full-field white light stimulation were investigated in the chicken retina. Pharmacological studies and cross-correlation analysis demonstrated that application of the GABA(A) receptor antagonist bicuculline (BIC) significantly down-regulated the correlation strength while increasing the firing activities. Meanwhile, application of the GABA(A) receptor agonist muscimol (MUS) potentiated the correlated activities while decreasing the firing rates. However, application of the GABA(C) receptor antagonist (1,2,5,6-Tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) did not have a consistent influence on either the firing rates or the correlation strength. These results suggest that in the chicken retina, correlated activities among neighborhood transient ganglion cells can be increased while firing activities are reduced with the activation of GABA(A) receptors. The GABA(A)-receptor-mediated inhibitory pathway may be critical for improving the efficiency of visual information transmission.
Action Potentials ; Animals ; Bicuculline ; pharmacology ; GABA-A Receptor Antagonists ; pharmacology ; Mice ; Muscimol ; pharmacology ; Phosphinic Acids ; pharmacology ; Pyridines ; pharmacology ; Receptors, GABA-A ; metabolism ; Retina ; physiology ; Retinal Ganglion Cells ; physiology ; gamma-Aminobutyric Acid

Animals ; Anticonvulsants ; pharmacology ; Drug Evaluation, Preclinical ; methods ; GABA-A Receptor Antagonists ; pharmacology ; Motor Activity ; drug effects ; Pentylenetetrazole ; pharmacology ; Valproic Acid ; pharmacology ; Zebrafish

.This study is to investigate the analgesic effect produced by intrathecal injection (ith) of oxysophoridine (OSR) and the mechanism of GABAA receptor. Warm water tail-flick test was used to detect the analgesic effect of OSR (12.5, 6.25, and 3.13 mg.kg-1 ith) and to observe the influence of GABA (gamma aminobutyric acid) agonist or antagonist on the analgesic effect of OSR in mice. Immunohistochemistry method were used to detect the influence of OSR (12.5 mg.kg-1, ith) on the GABAARalpha1 protein expression in spinal cord. The results obtained covers that OSR (12.5 and 6.25 mg.kg-, ith) alleviates pain significantly with the warm water tail-flick test (P<0.05, P<0.01), the rate of pain threshold increases by 68.45%; GABA and muscimol (MUS) produces analgesic synergism together with the OSR, picrotoxin (PTX) and bicuculline (BIC) antagonize the analgesic effect of OSR; OSR (12.5 mg.kg-1, ith) significantly increase the positive number of GABAARalpha1 nerve cell in spinal cord (P<0.01) and significantly decrease the average grey levels (P<0.01). In conclusion, OSR intrathecal injection has significant analgesic effect. And GABAA receptor in spinal cord is involved in the analgesic mechanism.
Alkaloids ; administration & dosage ; pharmacology ; Analgesics ; administration & dosage ; pharmacology ; Animals ; Bicuculline ; pharmacology ; Female ; GABA-A Receptor Agonists ; pharmacology ; GABA-A Receptor Antagonists ; pharmacology ; Injections, Spinal ; Male ; Mice ; Muscimol ; pharmacology ; Pain Threshold ; drug effects ; Picrotoxin ; pharmacology ; Random Allocation ; Receptors, GABA-A ; metabolism ; Spinal Cord ; metabolism ; gamma-Aminobutyric Acid ; pharmacology

Since GABA and its related enzymes had been determined in beta-cells of pancreas islets, effects of GABA on pancreatic exocrine secretion were investigated in the isolated perfused rat pancreas. GABA, given intra-arterially at concentrations of 3, 10, 30 and 100 microM, did not exert any influence on spontaneous or secretin (12 pM)-induced pancreatic exocrine secretion. However, GABA further elevated cholecystokinin (10 pM)-, gastrin-releasing peptide (100 pM)- or electrical field stimulation-induced pancreatic secretions of fluid and amylase, dose-dependently. The GABA-enhanced CCK-induced pancreatic secretions were completely blocked by bicuculline (10 microM), a GABAA receptor antagonist but not affected by saclofen (10 microM), a GABA(B) receptor antagonist. The enhancing effects of GABA (30 microM) on CCK-induced pancreatic secretions were not changed by tetrodotoxin (1 microM) but partially reduced by cyclo-(7-aminoheptanonyl-Phe-D-Trp-Lys-Thr[BZL]) (10 microM), a somatostatin antagonist. In conclusion, GABA enhances pancreatic exocrine secretion induced by secretagogues, which stimulate enzyme secretion predominantly, via GABA(A) receptors in the rat pancreas. The enhancing effect of GABA is partially mediated by inhibition of islet somatostatin release. GABA does not modify the activity of intrapancreatic neurons.
Amylases/metabolism ; Animal ; Baclofen/pharmacology ; Baclofen/analogs & derivatives* ; Bicuculline/pharmacology ; Cholecystokinin/metabolism ; Dose-Response Relationship, Drug ; Electric Stimulation ; GABA/pharmacology* ; GABA Antagonists/pharmacology ; Gastrin-Releasing Peptide/metabolism ; Hormones/pharmacology ; In Vitro ; Pancreas/secretion* ; Pancreas/enzymology ; Pancreas/drug effects* ; Rats ; Receptors, GABA-A/metabolism ; Secretin/metabolism ; Somatostatin/pharmacology ; Tetrodotoxin/pharmacology

OBJECTIVETo investigate the pharmacological modulatory properties of noradrenaline in the rat spiral ganglion neuron.

METHODSNystatin perforated patch recording technique under voltage-clamp conditions was used to record the modulatory effect of noradrenaline on the current evoked by gamma-amino butyric acid (GABA) in the spiral ganglion neuron.

RESULTSThe reversal potential of the GABA response was about (- 0.78 +/- 0.05) mV (n = 8), which was almost identical to the theoretical Cl- equilibrium potential. At the holding potential of -50 mV, GABA evoked inward current (I(GABA)) over the concentration range of 0.3 to 1 micromol/L. The EC50 and Hill coefficient for GABA were (5.2 +/- 0.5) micromol/L and 1.03 (n = 26). The I(GABA) was suppressed by bicuculline, the selective GABA-A receptor antagonist, and the chloride currents evoked by GABA was inhibited by noradrenaline.

CONCLUSIONSThe result indicates that noradrenaline depressed GABA-A receptor-gated chloride currents, which may contribute to the modulatory effect of sympathetic system on auditory transmission.

Animals ; Chloride Channels ; drug effects ; GABA-A Receptor Antagonists ; pharmacology ; Neurons ; drug effects ; metabolism ; Norepinephrine ; pharmacology ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA ; metabolism ; Spiral Ganglion ; drug effects

By means of whole-cell patch clamp technique, the modulatory effect of caffeine on GABA-activated currents (I(GABA)) was investigated in acutely isolated rat dorsal root ganglion (DRG) neurons. The majority of the neurons examined (113/116) were sensitive to GABA (1~1000 micromol/L). GABA activated a concentration-dependent inward current, which manifested obvious desensitization. In 58 out of 108 neurons, caffeine induced a small inward current, while in others no detectable current was observed. After the neurons were treated with caffeine (0.1~100 micromol/L) prior to the application of GABA (100 micromol/L) for 30 s, GABA-activated inward currents were obviously inhibited. Caffeine shifted the GABA dose-response curve downward and decreased the maximum response to 57% without changing K(d) value. These results indicate that the inhibitory effect is non-competitive. The pretreatment with caffeine (10 micromol/L) inhibited I(GABA) which was potentiated by diazepam (1 micromol/L). Intracellular application of H-8 almost completely abolished the inhibitory effect of caffeine on I(GABA). Because GABA can induce primary afferent depolarization (PAD), our results suggest that caffeine may be able to antagonize the effect of presynaptic inhibition of GABA in primary afferent.
Animals ; Animals, Newborn ; Caffeine ; pharmacology ; Cell Separation ; Cells, Cultured ; Electrophysiology ; GABA Antagonists ; pharmacology ; Ganglia, Spinal ; cytology ; physiology ; Neurons ; cytology ; physiology ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA-A ; physiology ; gamma-Aminobutyric Acid ; physiology

Experiments were performed on Sprague Dawley rats with multibarrel microelectrode technique. The effects of acoustic response of A I cortex neurons produced by electrical stimulation of lateral amygdaloid nucleus (LA) and the influence of GABA were observed. Experimental results showed that iontophoretic administration of GABA caused a pronounced inhibition of the electrical activity of A-I neurons. Blockade of GABA(A) with bicuculline (BIC) facilitated the acoustic response. The acoustic response of A-I neurons was inhibited when the LA was stimulated. Iontophoretic application of GABA resulted in a similar inhibitory effect as that of LA stimulation. Blockade of GABA(A) with bicuculline reversed the inhibitory effect of LA stimulation on the acoustic response of A-I neurons. In contrast, application of strychnine, a glycine receptor antagonist, could not reverse the inhibitory effect of LA. Baclofen, a GABA(B) agonist, did not affect the acoustic response of the auditory neurons. These results indicate that GABA is the ultimate transmitter which mediates the LA stimulation-induced inhibition of the acoustic response of A-I neurons in rats, possibly via the GABA(A) receptor.
Acoustic Stimulation ; Amygdala ; physiology ; Animals ; Baclofen ; pharmacology ; Bicuculline ; pharmacology ; Cerebral Cortex ; physiology ; Electric Stimulation ; Evoked Potentials, Auditory ; physiology ; GABA Agonists ; pharmacology ; GABA Antagonists ; pharmacology ; Iontophoresis ; methods ; Male ; Microelectrodes ; Neurons ; physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA-A ; physiology ; gamma-Aminobutyric Acid ; physiology

Exploring the transition from inter-ictal to ictal epileptiform discharges (IDs) and how GABA receptor-mediated action affects the onset of IDs will enrich our understanding of epileptogenesis and epilepsy treatment. We used Mg-free artificial cerebrospinal fluid (ACSF) to induce epileptiform discharges in juvenile mouse hippocampal slices and used a micro-electrode array to record the discharges. After the slices were exposed to Mg-free ACSF for 10 min-20 min, synchronous recurrent seizure-like events were recorded across the slices, and each event evolved from inter-ictal epileptiform discharges (IIDs) to pre-ictal epileptiform discharges (PIDs), and then to IDs. During the transition from IIDs to PIDs, the duration of discharges increased and the inter-discharge interval decreased. After adding 3 μmol/L of the GABA receptor agonist muscimol, PIDs and IDs disappeared, and IIDs remained. Further, the application of 10 μmol/L muscimol abolished all the epileptiform discharges. When the GABA receptor antagonist bicuculline was applied at 10 μmol/L, IIDs and PIDs disappeared, and IDs remained at decreased intervals. These results indicated that there are dynamic changes in the hippocampal network preceding the onset of IDs, and GABA receptor activity suppresses the transition from IIDs to IDs in juvenile mouse hippocampus.
Animals ; Animals, Newborn ; Bicuculline ; pharmacology ; Disease Models, Animal ; Epilepsy ; pathology ; GABA-A Receptor Agonists ; pharmacology ; GABA-A Receptor Antagonists ; therapeutic use ; Hippocampus ; drug effects ; metabolism ; physiopathology ; In Vitro Techniques ; Magnesium ; metabolism ; pharmacology ; Male ; Membrane Potentials ; drug effects ; Mice ; Mice, Inbred C57BL ; Muscimol ; pharmacology ; Nerve Net ; drug effects ; Receptors, GABA-A ; metabolism

The modulation by substance P of gamma-aminobutyric acid (GABA)- and 5-hydroxytryptamine (5-HT)-activated currents (I(GABA) and I(5-HT)) was studied by using patch-clamp technique in rat trigeminal ganglion (TG) neurons. The majority of neurons examined responded to GABA and 5-HT with inward currents in the same cells (63.8%, 30/47). In 22 out of 30 neurons sensitive to both GABA and 5-HT, pretreatment with substance P (SP, 0.01 micromol/L) suppressed I(GABA) by (35.7 +/-6.1)% and enhanced I(5-HT) by (65.2 +/- 8.7)%. GR 82334, a potent and specific antagonist of NK1 tachykinin receptor, reversibly blocked the modulatory effects of SP. The SP modulation on I(GABA) and I(5-HT) was also abolished by intracellular dialysis of GDP-beta-S, a non-hydrolyzable GDP analog, or GF 109203X, a selective protein kinase C inhibitor. These results suggest that SP exerts opposite modulatory actions on GABA(A) receptor and 5-HT3 receptor activity of the same primary sensory neuron via the same intracellular signal transduction pathway.
Animals ; Animals, Newborn ; GABA Antagonists ; pharmacology ; Neurons, Afferent ; physiology ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Serotonin ; physiology ; Serotonin Antagonists ; pharmacology ; Substance P ; pharmacology ; physiology ; Trigeminal Ganglion ; physiology ; gamma-Aminobutyric Acid ; physiology