• Archives of Pharmacal Research
• /
• v.28 no.5
• /
• pp.587-591
• /
• 2005

The effect of extremely low frequency (ELF,60Hz) magnetic fields (MFs) on convulsions was investigated in rats. We determined the onset arid duration of convulsions induced by bicuculline alone or by co-exposure to MFs and bicuculline. In addition, we measured the GABA concentrations in the rat brains using HPLC-ECD. MFs strengthened the convulsion induced by bicuculline (0.3, 1, and 3${\mu}g$, I.c.v.), with a shortening of the onset time, but lengthening of the duration time. Co-exposure to MFs and bicuculline decreased the GABA levels in the cortex, hippocampus and hypothalamus, whereas MFs alone reduced the level of GABA only in the hippocampus. These results suggest that the exposure to MFs may modulate bicuculline-induced convulsions due to GABA neurotransmissions in rat brains.

• The Korean Journal of Pharmacology
• /
• v.29 no.1
• /
• pp.23-32
• /
• 1993

Recent studies have shown that a GABAergic mechanism in the brain modulates arterial blood pressure (BP) through alterations of sympathetic activity in the brain. The purpose of the present study was to determine if this modulation is involved in the pressor response to raised intracranial pressure (ICP). The pressor response to raised ICP was abolished by pretreatment of anesthetized rabbits with intracerebroventricular (icv) muscimol (a GABA agonist) as well as with icv clonidine $(an\;{\alpha}_2-agonist)$. Raising ICP in the hypertensive state after icv yohimbine $(an\;{\alpha}_2-antagonist)$ did not cause an additional increase in the BP, whereas raising ICP in the hypertensive state following icv bicuculline (a GABA antagonist) produced a further increase. Bicuculline produced an increase of the BP which had been lowered by muscimol or by clonidine, whereas it failed to increase the hypertensive state induced by either previous yohimbine or raised ICP. Yohimbine reversed the BP which had been made low by clonidine but was incapable of raising the hypotensive state after muscimol. Yohimbine failed to increase the heightened BP due to raised ICP, whereas bicuculline-induced pressor state was further elevated by yohimbine. Muscimol, besides the bicuculline-antagonizing property, inhibited the pressor response to yohimbine, suggesting participation of a GABAergic mechanism in the pressor action of yohimbine. From these results it was inferred that there were three ways in which BP could be increased via raised ICP: inactivation of the inhibitory sympathetic activity through (1) ${\alpha}_{2}-adrenoceptors$, (2) bicuculline-sensitive GABA receptors, (3) yohimbine-sensitive, clonidine-acting GABAergic sites.

• The Korean Journal of Pain
• /
• v.11 no.1
• /
• pp.23-29
• /
• 1998

Background: The present study was conducted to investigate effects of microinjection of bicuculline, GABA-A receptor antagonist, into the brain stem nuclei on the dorsal horn neuron responsiveness in rats with an experimental peripheral neuropathy. Methods: An experimental neuropathy was induced by a unilateral ligation of L5~L6 spinal nerves of rats. After 2~3 weeks after the surgery, single-unit recording was made from wide dynamic range (WDR) neurons in the spinal cord dorsal horn. Results: Responses of WDR neurons to both noxious and innocuous mechanical stimuli applied to the somatic receptive fields were enhanced on the nerve injured side. These enhanced responsiveness of WDR neurons were suppressed by microinjection of bicuculline into periaqueductal gray(PAG) or nucleus reticularis gigantocellularis(Gi). A similar suppression was also observed when morphine was microinjected into PAG or Gi. Suppressive action by Gi-bicuculline was reversed by naloxonazine, ${\mu}$-opioid receptor antagonist, microinjected into PAG whereas PAG-bicuculline induced suppression was not affected by naloxonazine injection into Gi. Gi-bicuculline induced suppression were reversed by a transection of dorsolateral funiculus(DLF) of the spinal cord. Conclusions: The results suggest that endogenous opioids, via acting on GABAergic interneurons in PAG and Gi, may be involved in the control of neuropathic pain by activating the descending inhibitory pathways that project to the spinal dorsal horn through DLF to inhibit the responsiveness of WDR neurons.

• International Journal of Oral Biology
• /
• v.33 no.4
• /
• pp.217-221
• /
• 2008

Bicuculline is one of the most commonly used $GABA_A$ receptor antagonists in electrophysiological research. Because of its poor water solubility, bicuculline quaternary ammonium salts such as bicuculline methiodide (BMI) and bicuculline methbromide are preferred. However, a number of studies have shown that BMI has non-$GABA_A$ receptor-mediated effects. The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) is implicated in the processing of nociceptive signaling. In this study, we investigated whether BMI has non-GABA receptor-mediated activity in Vc SG neurons using a whole cell patch clamp technique. SG neurons were depolarized by application of BMI ($20{\mu}M$) using a high $Cl^-$ pipette solution. GABA ($30-100{\mu}M$) also induced membrane depolarization of SG neuron. Although BMI is known to be a $GABA_A$ receptor antagonist, GABA-induced membrane depolarization was enhanced by co-application with BMI. However, free base bicuculline (fBIC) and picrotoxin (PTX), a $GABA_A$ and $GABA_C$ receptor antagonist, blocked the GABA-induced response. Furthermore, BMI-induced membrane depolarization persisted in the presence of PTX or an antagonist cocktail consisting of tetrodotoxin ($Na^+$ channel blocker), AP-5 (NMDA receptor antagonist), CNQX (non-NMDA receptor antagonist), and strychnine (glycine receptor antagonist). Thus BMI induces membrane depolarization by directly acting on postsynaptic Vc SG neurons in a manner which is independent of $GABA_A$ receptors. These results suggest that other unknown mechanisms may be involved in BMI-induced membrane depolarization.

• Journal of Chest Surgery
• /
• v.31 no.5
• /
• pp.441-450
• /
• 1998

The medullospinal tract cells are known to play an important role in the control of the cardiovascular activities. To clarify the modes of action of the neurotransmitters on these cells, glutamate, GABA(${\gamma}$-aminobutyric acid) and bicuculline were applicated iontophoretically into the rostral ventrolateral medulla in adult cats anesthetised with ${\alpha}$-chloralose. Followings are the results obtained : 1. The spontaneous activities of the cardiac-related neurons in rostral ventrolateral medulla (RVLM) were increased by the glutamate and decreased by the GABA. 2. Bicuculline, an antagonist of GABA, alone didn't increase the frequency of the action potentials, but could reverse the cellular response to the GABA, simultaneously applicated. 3. GABA seemed to decrease the peak as well as the basal discharge of the neurons in RVLM, but hardly changed their periodicities. 4. The cellular responses of RVLM evoked by the peripheral nerve stimulation could be inhibited by the iontophoretically released GABA. In conclusion, GABA seemed to act as an inhibitory neurotransmitter on the cardiac- related neurons in RVLM of the cats anesthetized with ${\alpha}$-chloralose. But the maintenance of the periodicities of these cells after the application of bicuculline suggested that the afferent activity of the baroreceptor didn't play a key role in the spontaneous activities of the RVLM neurons.

• Journal of the korean academy of Pediatric Dentistry
• /
• v.27 no.1
• /
• pp.7-14
• /
• 2000

Inhibitory cells are critically involved in shaping normal hippocampal function and are thought to be important elements in the development of hippocampal pathologies. The present study was carried out in hippocampal CA1 area in vivo to compare with hippocampal slice studies. Intracellular and extracellular recordings with or without bicuculline electrodes were obtained in the intact brain of anesthetized rats, and cells were intracellularty labelled with neurobiotin. Electrical stimulation of fimbria-fornix resulted in an initial short-latency population spike. In the presence of $10{\mu}M$ bicuculline, orthodromic stimulation resulted in bursts of population spikes. The amplitude of population spikes in the CA1 region increased with stimulus intensity, as did the number of population spikes when the field recording electrode contained $10{\mu}M$ bicuculline. We measured the level of excitability in the CA1 area, using a paired-pulse stimulus paradigm to evoke population spikes. Population spikes showed strong paired-pulse inhibition at short interstimulus intervals. Burst afterdischarges up to 400 ms were observed after paired-pulse stimulus. These result suggest that hippocampal CA1 inhibitory interneurons can affect the excitability of pyramidal neurons that can not be appreciated in conventional in vitro preparation.

• The Korean Journal of Physiology and Pharmacology
• /
• v.8 no.3
• /
• pp.129-132
• /
• 2004

Single unit responses of the ventral posterior medial (VPM) thalamic neurons to stimulation were monitored in anesthetized rats during activation of contralateral primary somatosensory (SI) cortex by GABA antagonist. The temporal changes of afferent sensory transmission were quantitatively analyzed by poststimulus time histogram (PSTH). Mainly, afferent sensory transmission to VPM thalamus was facilitated (15 neurons of total 23) by GABA antagonist (bicuculline) applied to contralateral cortex, while 7 neurons were suppressed. However, when ipsilateral cortex was inactivated by GABA agonist, musimol, there was significant suppression of afferent sensory transmission of VPM thalamus. This suppressed responsiveness by ipsilateral musimol was not affected by bicuculline applied to contralateral cortex. These results suggest that afferent transmission to VPM thalamus may be subjected to the interhemispheric modulation via ipsilateral cortex during inactivation of GABAergic neurons in contralateral SI cortex.

• The Journal of Korean Medicine
• /
• v.19 no.2
• /
• pp.450-467
• /
• 1998

To research the characteristics of ion currents induced by inhibitory and excitatory herbs of oriental medicine, we used nystatin-perforated patch clamp technique under voltage clamp condition in periaqueductal gray neuron dissociated from Sprauge-Dawley rat, 10-15 days old. The results are as follows. 1. Ion current induced by $10mg/m{\ell}$ of Bupleuri Radix was inhibited $59.50{\pm}4.29%$ by $10^{-4}M$ bicuculline(p>0.01) but inhibition of $10.75{\pm}4.77%$ by $10^{-4}M$ tubocurarine and $4.75{\pm}4.23%$ by $10^{-4}M$ verapamil had no statistical significance(p>0.05). So ion current induced by Bupleuri Radix revealed only GABA induced $Cl^-$ current, not acetylcholine and $Ca^{2+}$ current. 2. Ion current induced by $20mg/m{\ell}$ of Coptidis Rhizoma was inhibited $47.20{\pm}7.88%$ by $10^{-4}M$ bicuculline(p<0.01) but $3.20{\pm}2.33%$ inhibition by $10^{-4}M$ tubocurarine and $1.00{\pm}1.00%$ inhibition by $10^{-4}M$ verapamil had no significance(p>0.05). So ion current induced by Coptidis Rhizoma revealed only GABA induced $Cl^-$ current, not acetylcholine and $Ca^{2+}$ current. 3. Ion current induced by $20mg/m{\ell}$ of Ecliptae Herba was inhibited $55.00{\pm}4.92%$ by $10^{-4}M$ bicuculline (p<0.01), and also inhibited $15.00{\pm}4.26%$ by $10^{-4}M$ tubocurarine(p<0.05), but inhibition of $6.00{\pm}3.03%$ by $10^{-4}M$ verapamil had no significance(p>0.05). So ion current induced by Ecliptae Herba showed GABA activated $Cl^-$ current and acetylcholine activated cation current, not $Ca^{2+}$ current 4. Ion current induced by $5mg/m{\ell}$ of Liriopis Tuber was inhibited $15.20{\pm}4.57%$ by $10^{-4}M$ bicuculline<0.05) and also inhibited $14.00{\pm}3.00%$ by $10^{-4}M$ tubocurarine(p<0.05), but inhibition of $5.20{\pm}4.80%$ by $10^{-4}M$ verapamil had no significance(p>0.05). So ion current induced by Liriopis Tuber showed GABA. activated $Cl^-$ current and acetylcholine activated cation current, not $Ca^{2+}$ current. 5. Ion current induced by $5mg/m{\ell}$ of Aconiti Tuber was inhibited $97.00{\pm}1.34%$ by $10^{-4}M$ bicuculline(p<0.01), $80.00{\pm}9.83%$ by $10^{-4}M$ tubocurarine(p<0.01), and $24.00{\pm}6.18%$ by $10^{-4}M$ verapamil(p<0.05). So ion current induced by Aconiti Tuber revealed GABA activated $Cl^-$ current and acetylcholine activated cation current and $Ca^{2+}$ current. 6. Ion current induced by $10mg/m{\ell}$ of Zingiberis Rhizoma was inhibited $33.00{\pm}7.43%$ by $10^{-4}$ bicuculline(p<0.05), $10.20{\pm}1.83%$ by $10-^{-4}M$ tubocurarine(p<0.01), and $14.00{\pm}2.16%$ by $10^{-4}M$ verapamil(p<0.01) So ion current induced by Zingiberis Rhizoma revealed GABA activated $Cl^-$ current and acetylcholine activated cation outtent and $Ca^{2+}$ current. 7. Ion current induced by $10mg/m{\ell}$ of Boshniakiae Herba was inhibited $65.00{\pm}13.75%$ by $10^{-4}M$ bicuculline(p<0.05), $38.00{\pm}9.24%$ by $10^{-4}M$ tubocurarine(p<0.05), and $33.25{\pm}7.42%$ by $10^{-4}M$ verapamiHp<0.05). So ion current induced by Bpshniakiae Herba revealed GABA activated $Cl^-$ current and acetylcholine activated cation current and $Ca^{2+}$ current. These results suggest that a point of difference between inhibitory and excitatory herbs is existence of$Ca^{2+}$ current.

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.274.2-274.2
• /
• 2002

Some experiments have been reported that magnetic fields can cause the change of numerous neurotransmitters including excitatory and inhibitory transmitters, which are involved in seizures. In this study we aimed to examine the effect of extremely low frequency magnetic field (ELF-MF) on the sensitivity of seizure response to bicuculline, picrotoxin and NMDA in mice. Mouse were exposed to sham or 20 G ELF-MF for 24 hours and then convulsants were administered i.p. at various doses. (omitted)

• The Korean Journal of Physiology and Pharmacology
• /
• v.21 no.1
• /
• pp.65-74
• /
• 2017

Here we investigated the central processing mechanisms of mechanical allodynia and found a direct excitatory link with low-threshold input to nociceptive neurons. Experiments were performed on male Sprague-Dawley rats weighing 230-280 g. Subcutaneous injection of interleukin 1 beta ($IL-1{\beta}$) ($1ng/10{\mu}L$) was used to produce mechanical allodynia and thermal hyperalgesia. Intracisternal administration of bicuculline, a gamma aminobutyric acid A ($GABA_A$) receptor antagonist, produced mechanical allodynia in the orofacial area under normal conditions. However, intracisternal administration of bicuculline (50 ng) produced a paradoxical anti-allodynic effect under inflammatory pain conditions. Pretreatment with resiniferatoxin (RTX), which depletes capsaicin receptor protein in primary afferent fibers, did not alter the paradoxical anti-allodynic effects produced by the intracisternal injection of bicuculline. Intracisternal injection of bumetanide, an Na-K-Cl cotransporter (NKCC 1) inhibitor, reversed the $IL-1{\beta}$-induced mechanical allodynia. In the control group, application of GABA ($100{\mu}M$) or muscimol ($3{\mu}M$) led to membrane hyperpolarization in gramicidin perforated current clamp mode. However, in some neurons, application of GABA or muscimol led to membrane depolarization in the $IL-1{\beta}$-treated rats. These results suggest that some large myelinated $A{\beta}$ fibers gain access to the nociceptive system and elicit pain sensation via $GABA_A$ receptors under inflammatory pain conditions.