2-3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline and bicuculline-methiodide

G-protein-coupled receptors (GPCRs) may form heteromeric complexes and cooperatively mediate cellular responses. Although heteromeric GPCR complexes are suggested to occur in many neurons, their contribution to neuronal function remains unclear. We address this question using two GPCRs expressed in cerebellar Purkinje cells: adenosine A1 receptor (A1R), which regulates neurotransmitter release and neuronal excitability in central neurons, and type-1 metabotropic glutamate receptor (mGluR1), which mediates cerebellar long-term depression, a form of synaptic plasticity crucial for cerebellar motor learning. We examined interaction between these GPCRs by immunocytochemical, biochemical, and Förster resonance energy transfer analyses in cultured mouse Purkinje cells and heterologous expression cells. These analyses revealed that the GPCRs closely colocalized and formed heteromeric complexes on the cell surfaces. Furthermore, our electrophysiological analysis showed that CSF levels (40-400 nm) of adenosine or synthetic A1R agonists with comparable potencies blocked mGluR1-mediated long-term depression of the postsynaptic glutamate-responsiveness (glu-LTD) of cultured Purkinje cells. A similar dose of the A1R agonist decreased the ligand affinity of mGluR1 and did not affect depolarization-induced Ca(2+) influx, which is an essential factor in inducing glu-LTD. The A1R agonist did not affect glu-LTD mimicked by direct activation of protein kinase C. These results suggest that A1R blocked glu-LTD by decreasing the ligand sensitivity of mGluR1, but not the coupling efficacy from mGluR1 to the intracellular signaling cascades. These findings provide a new insight into neuronal GPCR signaling and demonstrate a novel regulatory mechanism of synaptic plasticity.

Topics: Animals; Bicuculline; Cells, Cultured; Cerebellum; Dose-Response Relationship, Drug; Embryo, Mammalian; Energy Transfer; Excitatory Amino Acid Antagonists; Green Fluorescent Proteins; Humans; Mice; Mice, Inbred C57BL; Neuronal Plasticity; Neurons; Neuroprotective Agents; Quinoxalines; Rats; Receptor, Adenosine A1; Receptors, Metabotropic Glutamate; Sodium Channel Blockers; Tetrodotoxin

The midbrain is an important processing area for sensory information in vertebrates. The optic tectum and its mammalian counterpart, the superior colliculus, receive multimodal, topographic information and contain a sensory map that plays a role in spatial attention and orientation movements. Many studies have investigated the tectal circuitry by cytochemistry and by characterization of particular cell types. However, only a few studies have investigated network activation throughout the depth of the tectum. Our study provides the first data on spatiotemporal activity profiles in the depth and width of the avian optic tectum. We used an optical imaging approach with voltage-sensitive dyes to investigate population responses at a high temporal and spatial resolution. With the necessary caution due to cell extension across several layers, we can thus link our findings tentatively with the general layout of the avian optic tectum. Single electrical stimuli in the retinorecipient layers 1-4 evoked a complex optical response pattern with two components: a short, strong transient response and a weaker persistent response that lasted several hundred milliseconds. The response started in layer 5 and spread within this layer before it propagated into deeper layers. This is in line with neuroanatomical and earlier physiological data. Analysis of temporal sequence and pharmacological manipulations revealed that these responses were mainly driven by postsynaptic activation. Thus tectal network responses to patterned input can be studied by voltage-sensitive dye imaging.

Topics: Animals; Animals, Newborn; Bicuculline; Brain Mapping; Calcium; Chickens; Electric Stimulation; Evoked Potentials, Visual; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; GABA-A Receptor Antagonists; In Vitro Techniques; Inhibitory Postsynaptic Potentials; Neurons; Quinoxalines; Superior Colliculi; Time Factors; Visual Pathways; Voltage-Sensitive Dye Imaging

Norepinephrine (NE) is widely implicated in various forms of associative olfactory learning in rodents, including early learning preference in neonates. Here we used patch-clamp recordings in rat olfactory bulb slices to assess cellular actions of NE, examining both acute, short-term effects of NE as well as the relationship between these acute effects and long-term cellular changes that could underlie learning. Our focus for long-term effects was on synchronized gamma frequency (30-70 Hz) oscillations, shown in prior studies to be enhanced for up to an hour after brief exposure of a bulb slice to NE and neuronal stimulation. In terms of acute effects, we found that a dominant action of NE was to reduce inhibitory GABAergic transmission from granule cells (GCs) to output mitral cells (MCs). This disinhibition was also induced by clonidine, an agonist specific for alpha(2) adrenergic receptors (ARs). Acute NE-induced disinhibition of MCs appeared to be linked to long-term enhancement of gamma oscillations, based, first, on the fact that clonidine, but not agonists specific for other AR subtypes, mimicked NE's long-term actions. In addition, the alpha(2) AR-specific antagonist yohimbine blocked the long-term enhancement of the oscillations due to NE. Last, brief exposure of the slice to the GABA(A) receptor antagonist gabazine, to block inhibitory synapses directly, also induced the long-term changes. Acute disinhibition is a plausible permissive effect of NE leading to olfactory learning, because, when combined with exposure to a specific odor, it should lead to neuron-specific increases in intracellular calcium of the type generally associated with long-term synaptic modifications.

Topics: Action Potentials; Adrenergic alpha-Agonists; Animals; Animals, Newborn; Bicuculline; Biological Clocks; Biophysical Phenomena; Electric Stimulation; Excitatory Amino Acid Antagonists; GABA Antagonists; GABA-A Receptor Antagonists; In Vitro Techniques; Inhibitory Postsynaptic Potentials; N-Methylaspartate; Neurons; Norepinephrine; Olfactory Bulb; Pyridazines; Quinoxalines; Rats; Receptors, Adrenergic; Valine

The superior colliculus (SC) is a midbrain structure that plays a role in converting sensation into action. Most SC research focuses on either in vivo extracellular recordings from behaving monkeys or patch-clamp recordings from smaller mammals in vitro. However, the activity of neuronal circuits is necessary to generate behavior, and neither of these approaches measures the simultaneous activity of large populations of neurons that make up circuits. Here, we describe experiments in which we measured changes in membrane potential across the SC map using voltage imaging of the rat SC in vitro. Our results provide the first high temporal and spatial resolution images of activity within the SC. Electrical stimulation of the SC evoked a characteristic two-component optical response containing a short latency initial-spike and a longer latency after-depolarization. Single-pulse stimulation in the superficial SC evoked a pattern of intralaminar and interlaminar spread that was distinct from the spread evoked by the same stimulus applied to the intermediate SC. Intermediate layer stimulation produced a more extensive and more ventrally located activation of the superficial layers than did stimulation in the superficial SC. Together, these results indicate the recruitment of dissimilar subpopulations of circuitry depending on the layer stimulated. Field potential recordings, pharmacological manipulations, and timing analyses indicate that the patterns of activity were physiologically relevant and largely synaptically driven. Therefore, voltage imaging is a powerful technique for the study of spatiotemporal dynamics of electrical signaling across neuronal populations, providing insight into neural circuits that underlie behavior.

Topics: 2-Amino-5-phosphonovalerate; Action Potentials; Anesthetics, Local; Animals; Bicuculline; Biophysical Phenomena; Brain Mapping; Diagnostic Imaging; Electric Stimulation; Evoked Potentials; Excitatory Amino Acid Antagonists; GABA Antagonists; In Vitro Techniques; Neural Conduction; Neural Pathways; Quinoxalines; Rats; Rats, Sprague-Dawley; Reaction Time; Superior Colliculi; Synapses; Tetrodotoxin

The molecular mechanisms controlling the termination of cortical interneuron migration are unknown. Here, we demonstrate that, prior to synaptogenesis, migrating interneurons change their responsiveness to ambient GABA from a motogenic to a stop signal. We found that, during migration into the cortex, ambient GABA and glutamate initially stimulate the motility of interneurons through both GABA(A) and AMPA/NMDA receptor activation. Once in the cortex, upregulation of the potassium-chloride cotransporter KCC2 is both necessary and sufficient to reduce interneuron motility through its ability to reduce membrane potential upon GABA(A) receptor activation, which decreases the frequency of spontaneous intracellular calcium transients initiated by L-type voltage-sensitive calcium channel (VSCC) activation. Our results suggest a mechanism whereby migrating interneurons determine the relative density of surrounding interneurons and principal cells through their ability to sense the combined extracellular levels of ambient glutamate and GABA once GABA(A) receptor activation becomes hyperpolarizing.

Topics: Age Factors; Animals; Animals, Newborn; Bicuculline; Calcium; Calcium Channel Blockers; Calcium Channels, L-Type; Cell Movement; Cerebral Cortex; Electroporation; Embryo, Mammalian; Female; GABA Agents; gamma-Aminobutyric Acid; Gene Expression Regulation; Glutamic Acid; Green Fluorescent Proteins; Homeodomain Proteins; Interneurons; K Cl- Cotransporters; LIM-Homeodomain Proteins; Membrane Potentials; Mice; Mice, Inbred BALB C; Mice, Transgenic; Microtubule-Associated Proteins; Models, Biological; Muscimol; Nerve Tissue Proteins; Nifedipine; omega-Conotoxin GVIA; Organ Culture Techniques; Pregnancy; Quinoxalines; Receptors, N-Methyl-D-Aspartate; RNA, Small Interfering; Sequence Deletion; Symporters; Transcription Factors; Valine

Odor coding in mammals is widely believed to involve synchronized gamma frequency (30-70 Hz) oscillations in the first processing structure, the olfactory bulb. How such inputs are read in downstream cortical structures however is not known. Here we used patch-clamp recordings in rat piriform cortex slices to examine cellular mechanisms that shape how the cortex integrates inputs from bulb mitral cells. Electrical stimulation of mitral cell axons in the lateral olfactory tract (LOT) resulted in excitation of pyramidal cells (PCs), which was followed approximately 10 ms later by inhibition that was highly reproducible between trials in its onset time. This inhibition was somatic in origin and appeared to be driven through a feedforward mechanism, wherein GABAergic interneurons were directly excited by mitral cell axons. The precise inhibition affected action potential firing in PCs in two distinct ways. First, by abruptly terminating PC excitation, it limited the PC response to each EPSP to exactly one, precisely timed action potential. In addition, inhibition limited the summation of EPSPs across time, such that PCs fired action potentials in strong preference for synchronized inputs arriving in a time window of <5 ms. Both mechanisms would help ensure that PCs respond faithfully and selectively to mitral cell inputs arriving as a synchronized gamma frequency pattern.

Topics: Action Potentials; Animals; Animals, Newborn; Bicuculline; Cerebral Cortex; Dose-Response Relationship, Radiation; Electric Stimulation; Excitatory Amino Acid Antagonists; GABA Antagonists; gamma-Aminobutyric Acid; In Vitro Techniques; Lysine; Models, Neurological; Nerve Net; Neurons; Olfactory Pathways; Patch-Clamp Techniques; Piperidines; Quinoxalines; Rats; Rats, Sprague-Dawley; Triazines

Reflex plasticity between pelvic afferent nerve (PAN) and pudendal efferent nerve (PEN), as well as external-urethral sphincter (EUS) activity was examined in anesthetized rats. A progressive increase in the number of evoked action potentials per stimulus occurred in PEN and EUS activity when PAN was repetitively stimulated (1 Hz). This potentiation in pelvic-pudendal reflex (PPR) activity induced by repetitive stimulation was abolished by APV (D-2-amino-5-phosphonoraleric acid, i.t. 100 microM, 2-5 microl) and attenuated by the NBQX (2, 3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline, i.t. 20 microM, 2-5 microl) but was not affected by the presence of bicuculline (i.t. 10 microM, 2-5 microl). The duration of contraction wave of intra-urethral pressure (IUP) elicited by a single electric shock was elongated by potentiated PPR, while the peak pressure was not affected. Both intrathecal application of glutamate (i.t. 0.1 mM, 2-5 microl) and NMDA (N-methyl-D-aspartic acid, i.t. 0.1 mM, 2-5 microl) induced spontaneous repetitive (0.31+/-0.02 Hz) burst discharges in PEN and EUSE and produced small contraction wave in IUP, which is similar to the high frequency oscillation phase during a voiding cycle of urinary bladder in rats. All these results demonstrate that repetitive stimulation of PAN can induce a distinct and long-lasting modulation in PPR activity and this change may be physiologically relevant in urinary continence.

Topics: 2-Amino-5-phosphonovalerate; Action Potentials; Anesthesia; Animals; Bicuculline; Dose-Response Relationship, Drug; Electric Stimulation; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Female; Glutamic Acid; Laminectomy; N-Methylaspartate; Neural Pathways; Neuronal Plasticity; Pelvis; Quinoxalines; Rats; Rats, Wistar; Reflex; Urethra

Using rapid agonist applications to transfected HEK-293 cells, we investigated pregnenolone sulfate (PS) effects on deactivation and desensitization of recombinant NMDA receptors subtypes. PS prolonged the deactivation of responses produced by brief applications of L-glutamate with all subunit combinations tested. The action of PS was larger on NR1a/NR2A than on NR1a/NR2B channels. PS slowed the rate of macroscopic desensitization of the responses with all subunit combinations tested. In contrast, PS had little effect on current rise time and had much reduced action on responses with L-cysteate, a low affinity agonist. Our results suggest that PS decreases agonist unbinding. However, this action is counteracted by decreased desensitization. Since desensitization produces slow deactivating components, particularly with NR1a/NR2B receptors, this underlies the decreased PS effect with these subtypes. Indeed PS action was mainly observed on the fast component of deactivation. Furthermore, prolongation of NR1a/NR2A responses was similar to that of responses from NR1b/NR2B receptor, a subtype characterized by reduced desensitization. PS prolongation of evoked NMDA receptor mediated synaptic currents from cortical neuronal primary culture(s) was not significantly different from that of responses with NR1a/NR2B receptors indicating that native receptors in these neurons comprised at least some heteromeric combinations of these two subunits.

Topics: Animals; Animals, Newborn; Bicuculline; Cell Line; Cells, Cultured; Cerebral Cortex; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Glutamic Acid; Humans; Membrane Potentials; Neurons; Patch-Clamp Techniques; Piperazines; Pregnenolone; Protein Subunits; Quinoxalines; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Time Factors

The main olfactory bulb is a critical relay step between the olfactory epithelium and the olfactory cortex. A marked feature of the bulb is its massive innervation by cholinergic inputs from the basal forebrain. In this study, we addressed the functional interaction between cholinergic inputs and intrinsic bulbar circuitry. Determining the roles of acetylcholine (ACh) requires the characterization of cholinergic effects on both neural excitability and synaptic transmission. For this purpose, we used electrophysiological techniques to localize and characterize the diverse roles of ACh in mouse olfactory bulb slices. We found that cholinergic inputs have a surprising number of target receptor populations that are expressed on three different neuronal types in the bulb. Specifically, nicotinic acetylcholine receptors excite both the output neurons of the bulb, i.e., the mitral cells, as well as interneurons located in the periglomerular regions. These nicotine-induced responses in interneurons are short lasting, whereas responses in mitral cells are long lasting. In contrast, muscarinic receptors have an inhibitory effect on the firing rate of interneurons from a deeper layer, granule cells, while at the same time they increase the degree of activity-independent transmitter release from these cells onto mitral cells. Cholinergic signaling thus was found to have multiple and opposing roles in the olfactory bulb. These dual cholinergic effects on mitral cells and interneurons may be important in modulating olfactory bulb output to central structures required for driven behaviors and may be relevant to understanding mechanisms underlying the perturbations of cholinergic inputs to cortex that occur in Alzheimer's disease.

Topics: 2-Amino-5-phosphonovalerate; Acetylcholine; Animals; Bicuculline; Calcium; Carbachol; gamma-Aminobutyric Acid; In Vitro Techniques; Interneurons; Kinetics; Magnesium; Mecamylamine; Mice; Mice, Inbred C57BL; Models, Neurological; N-Methylaspartate; Neurons; Olfactory Bulb; Patch-Clamp Techniques; Quinoxalines; Receptors, GABA-A; Receptors, Nicotinic; Synapses

The role of excitatory amino acid (EAA) receptors in the dorsomedial hypothalamus (DMH) in mediating the cardiovascular response to activation of the basolateral amygdala (BLA) was examined using conscious rats. Microinjection of the nonselective EAA receptor antagonist kynurenic acid (0.1-10 nmol) into the DMH blocked or reversed the increases in heart rate and arterial pressure resulting from injection of the GABAA receptor antagonists bicuculline methiodide (BMI; 100 pmol) and picrotoxin (100 pmol) into the BLA. Similar injections of kynurenic acid at sites lateral or dorsal to the DMH or injection of the inactive analog xanthurenic acid into the DMH were less effective in blocking the cardiovascular changes resulting from intra-amygdalar injection of BMI. Hypothalamic injection of the NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (10 pmol) or the DL-alpha-amino-3-hydroxy-5-methylisoxazole-propionic acid receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2, 3-dioxo-benzo[f]quinoxaline-7-sulfonamide (50 pmol) at doses shown to be selective for their respective EAA receptor subtypes attenuated the cardiovascular changes associated with intra-amygdalar injection of BMI. Therefore, EAA receptors in the area of the DMH appear to be involved in mediating the cardiovascular changes resulting from activation of the amygdala.

Topics: Amygdala; Animals; Bicuculline; Brain Mapping; Dorsomedial Hypothalamic Nucleus; Excitatory Amino Acid Antagonists; GABA-A Receptor Antagonists; Heart Rate; Kynurenic Acid; Male; Microinjections; Picrotoxin; Piperazines; Quinoxalines; Rats; Rats, Sprague-Dawley; Receptors, Amino Acid; Time Factors

We evaluate a novel set-up for scanning functional connectivity in brain slices from the somatosensory cortex of the rat. Upright infrared video microscopy for targeted placement of electrodes is combined with rapid photolysis of bath-applied caged neurotransmitter induced by a xenon flash lamp. Flash photolysis of caged glutamate and electrical stimulation produce comparable field potential responses and demonstrate that the viability of the submerged slices exceeds several hours. Glutamate release leads to field potential responses whose two phases are differentially affected by selective blockade of N-methyl-D-aspartate- and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate-type glutamate receptors with DL-2-amino-5-phosphonovaleric acid and 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulphonamide, respectively. Rapid computer-controlled scanning of hundreds of distinct stimulation sites with simultaneous recordings at a fixed reference site allows construction of functional input maps from peak amplitudes and delays to peak of field potential responses. Selective laminar expansion of the functional input maps after bicuculline application demonstrates that the combination of this conveniently assembled set-up with pharmacological and physical manipulations can provide insights into the determinants of functional connectivity in brain slices.

Topics: 2-Amino-5-phosphonovalerate; Animals; Bicuculline; Electric Stimulation; Evoked Potentials; Glutamic Acid; In Vitro Techniques; Membrane Potentials; Microscopy, Video; Photolysis; Quinoxalines; Rats; Receptors, Glutamate; Somatosensory Cortex; Tetrodotoxin

Limbic motor seizures in animals, analogous to complex partial seizures in humans, result in a consistent activation of the mediodorsal thalamus (MD) and, with prolonged seizures, damage to MD. This study examined the functional role of MD in focally evoked limbic motor seizures in the rat. GABA- and glutamate (Glu)-mediated synaptic transmissions in MD were evaluated for an influence on seizures evoked from area tempestas (AT), a discrete epileptogenic site in the rostral piriform cortex. A GABAA receptor agonist, Glu receptor antagonists, or a GABA-elevating agent were focally microinfused into MD before evoking seizures by focal application of bicuculline methiodide into the ipsilateral AT. Focal pretreatment of MD with the GABAA agonist muscimol (190 pmol) protected against seizures evoked from AT. Seizure protection was also obtained with the focal application of 2, 3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) (500 pmol), an antagonist of the AMPA subtype of Glu receptors, into MD. In contrast, focal pretreatment of MD with a competitive antagonist of the NMDA receptor 2-amino-7-phosphonoheptanoic acid (500 pmol) did not attenuate seizures. The anticonvulsant effects achieved with intra-MD injections of muscimol and NBQX were site-specific, because no seizure protection was obtained with injections placed 2 mm ventral or lateral to MD. Prolonged seizure protection was obtained following GABA elevation in MD after the application of the GABA transaminase inhibitor vigabatrin (194 nmol). These results suggest the following: (1) MD is a critical participant in the generation of seizures elicited focally from piriform cortex; (2) transmission via AMPA receptors, but not NMDA receptors, in MD regulates limbic seizure propagation; and (3) a GABA-mediated system exists within MD, the enhancement of which protects against focally evoked limbic motor seizures.

Topics: 2-Amino-5-phosphonovalerate; Animals; Anticonvulsants; Bicuculline; Brain Mapping; Carbon Radioisotopes; Deoxyglucose; Excitatory Amino Acid Antagonists; gamma-Aminobutyric Acid; Glutamic Acid; Limbic System; Male; Muscimol; Quinoxalines; Rats; Rats, Sprague-Dawley; Seizures; Thalamus; Time Factors; Vigabatrin

Entorhinal cortex layer III cells send their axons into hippocampal area CA1, forming the less well studied branch of the perforant path. Using electrophysiological and morphological techniques within a slice preparation, we can classify medial entorhinal cortex layer III cells into four different types. Type 1 and 2 cells were projection cells. Type 1 cells fired regularly and possessed high input resistances and long membrane time constants. Electrical stimulation of the lateral entorhinal cortex revealed a strong excitation by both N-methyl-D-aspartate and non-N-methyl-D-aspartate receptor-mediated excitatory postsynaptic potentials. Type 2 cells accommodated strongly, had lower input resistances, faster time constants and featured prominent synaptic inhibition. Type 1 and 2 cells responded to repetitive synaptic stimulation with a prolonged hyperpolarization. We identified the two other, presumed local circuit, cell types whose axons remained within the entorhinal cortex. Type 3 cells were regular firing, had high input resistances and slow membrane time constants, while type 4 cells fired at higher frequencies and possessed a faster time constant and lower input resistance than type 3 neurons. Type 3 cells presented long-lasting excitatory synaptic potentials. Type 4 neurons were the only ones with different responses to stimulation from different sites. Upon lateral entorhinal cortex stimulation they responded with an excitatory postsynaptic potential, while a monosynaptic inhibitory postsynaptic potential was evoked from deep layer stimulation. In contrast to type 1 and 2 neurons, none of the local circuit cells could be antidromically activated from deep layers, and prolonged hyperpolarizations following synaptic repetitive stimulation were also absent in these cells. Together, the complementing morphology and the electrophysiological characteristics of all the cells can provide the controlled flexibility required during the transfer of cortical information to the hippocampus.

Topics: 2-Amino-5-phosphonovalerate; 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Bicuculline; Electric Stimulation; Entorhinal Cortex; Excitatory Amino Acid Antagonists; Female; GABA Antagonists; In Vitro Techniques; Membrane Potentials; Neurons; Organophosphorus Compounds; Phosphinic Acids; Propanolamines; Quinoxalines; Rats; Rats, Wistar; Receptors, GABA-A; Receptors, GABA-B; Synaptic Transmission

Activation of the amygdala in rats produces cardiovascular changes that include increases in heart rate and arterial pressure as well as behavioral changes characteristic of emotional arousal. The objective of the present study was to examine the interaction of GABA and excitatory amino acid (EAA) receptors in the basolateral amygdala (BLA) in regulating cardiovascular function. Microinjection of the GABAA receptor antagonist bicuculline methiodide (BMI) or the E A A receptor agonists NMDA or AMPA into the same region of the BLA of conscious rats produced dose-related increases in heart rate and arterial pressure. Injection of the nonselective EAA receptor antagonist kynurenic acid into the BLA prevented or reversed the cardiovascular changes caused by local injection of BMI or the noncompetitive GABA antagonist picrotoxin. Conversely, local pretreatment with the glutamate reuptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid enhanced the effects of intra-amygdalar injection of BMI. The cardiovascular effects of BMI were also attenuated by injection of either the NMDA antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) or the AMPA receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2, 3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX). When these two EAA receptor antagonists were combined, their ability to suppress BMI-induced tachycardic and pressor responses was additive. These findings indicate that the cardiovascular effects caused by blockade of GABAergic inhibition in the BLA of the rat are dependent on activation of local NMDA and AMPA receptors.

Topics: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Amygdala; Animals; Arousal; Bicuculline; Blood Pressure; Dicarboxylic Acids; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; GABA Antagonists; gamma-Aminobutyric Acid; Heart Rate; Hemodynamics; Kynurenic Acid; Male; N-Methylaspartate; Neurotransmitter Uptake Inhibitors; Picrotoxin; Piperazines; Pyrrolidines; Quinoxalines; Rats; Rats, Sprague-Dawley; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate