6-cyano-7-nitroquinoxaline-2-3-dione and glutamic-acid-diethyl-ester

Neurotransmitters relaying ascending visceral information were examined by comparing the response of neurons in the insular cortex to vagal stimulation (0.8 Hz, 2 mA) before and after neurotransmitter antagonist injections (200 nl) in the ventroposterior parvocellular nucleus of the thalamus (VPpc). Cobalt (10 mM; presynaptic blocker) and kynurenate (100 microM; nonspecific excitatory amino acid antagonist) injections in the VPpc resulted in an attenuation (73-100 and 38-98%, respectively) of the evoked cortical response. Injections of the specific N-methyl-D-aspartate (NMDA) antagonist DL-2-amino-5-phosphonopentanoic acid (200 microM and 2 mM) did not affect the vagally evoked response, whereas the nonspecific non-NMDA antagonist L-glutamic acid diethylester (200 microM) attenuated the vagally evoked response by 66-100%. Three concentrations of the DL-alpha-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA)-specific antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (20 and 200 microM and 2 mM) attenuated the vagally evoked cortical response by 29 +/- 9, 31 +/- 10, and 59 +/- 8%, respectively. The more selective AMPA antagonist 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione (200 microM and 2 mM) inhibited the vagally evoked cortical response by 53 +/- 8 and 52 +/- 3%, respectively. Phentolamine (0.1 and 1.0 microM), a general alpha-adrenergic antagonist, and picrotoxin (0.1 and 1.0 microM), a GABA(A) antagonist, did not affect the vagally evoked response. Atropine, a muscarinic cholinergic antagonist, decreased the vagally evoked response by 40 +/- 2% at a concentration of 0.1 microM, but a higher concentration of 1.0 microM had no effect. These results indicate that the non-NMDA excitatory amino acid receptor is necessary for the relay of visceral information in the VPpc. Muscarinic receptors may modulate visceral neuronal excitability in the VPpc, although the exact interaction between the inhibitory (m2) and excitatory (m3 or m5) muscarinic receptor types found in the thalamus is not known.

Topics: 2-Amino-5-phosphonovalerate; 6-Cyano-7-nitroquinoxaline-2,3-dione; Adrenergic alpha-Antagonists; Animals; Atropine; Cerebral Cortex; Cobalt; Electric Stimulation; Excitatory Amino Acid Antagonists; GABA Antagonists; Glutamates; Kynurenic Acid; Male; Muscarinic Antagonists; Neurons; Neurotransmitter Agents; Phentolamine; Picrotoxin; Quinoxalines; Rats; Rats, Wistar; Thalamus; Vagus Nerve; Viscera

Microinjections of glutamate into the dorsal periaqueductal grey (DPAG) of rats induce flight behavior, and blockade of glutamate NMDA receptors in the same region increases exploratory behavior of rats tested on the elevated plus maze. To investigate a possible role of other glutamate receptors in the DPAG on anxiety modulation, rats (n = 6-10) received microinjections into this structure of CNQX (1 and 3 nmol/0.5 microl), an AMPA/kainate antagonist, or GDEE (80 or 160 nmol/0.5 microl), a non-selective glutamate antagonist, and were tested on the elevated plus-maze, an ethologically based animal model of anxiety. Both drugs increased the percentage of entries into open arms, as compared to rats receiving vehicle, without changing the number of enclosed arm entries. Injections of the active compounds outside the DPAG were not effective. The anxiolytic effect of CNQX (3 nmol/0.5 microl) was not reversed by glycine (10 nmol/0.5 microl), injected into the DPAG 5 min after CNQX administration. These results suggest that, in addition to NMDA receptors, non-NMDA glutamate receptors may also modulate anxiety in the DPAG.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Anxiety; Excitatory Amino Acid Antagonists; Exploratory Behavior; Glutamates; Injections, Intraventricular; Male; Mesencephalon; Rats; Rats, Wistar; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate

Topics: 2-Amino-5-phosphonovalerate; 6-Cyano-7-nitroquinoxaline-2,3-dione; Amino Acid Sequence; Animals; Blood Pressure; Excitatory Amino Acid Antagonists; Glutamates; Glutamic Acid; Heart Rate; Male; Medulla Oblongata; Molecular Sequence Data; N-Methylaspartate; Peptide Fragments; Quinoxalines; Rats; Receptors, N-Methyl-D-Aspartate; Reference Values; Stereotaxic Techniques; Substance P

L-Glutamate application can produce three different responses in the membrane potential of the Schwann cell of the tropical squid, Sepioteuthis sepioidea, which appear to be mediated by three pharmacologically distinct classes of receptor. A class of non-NMDA-type receptors, with some similarities to metabotropic glutamate receptors, mediates the development of a rapid and long-lasting hyperpolarization. Two pharmacologically distinct classes of NMDA-type receptor are present. One mediates the development of a slow depolarization accompanied by a long-lasting change in responsiveness of the Schwann cell. The second produces rapid depolarizing responses during the period of this changed responsiveness. All three types of receptor can be activated by dipeptides containing excitatory amino acids.

Topics: 2-Amino-5-phosphonovalerate; 6-Cyano-7-nitroquinoxaline-2,3-dione; Aminobutyrates; Animals; Axons; Decapodiformes; Dipeptides; Excitatory Amino Acid Antagonists; Glutamates; Glutamic Acid; Membrane Potentials; N-Methylaspartate; Quinoxalines; Receptors, Glutamate; Receptors, N-Methyl-D-Aspartate; Schwann Cells

The involvement of excitatory amino acid (EAA) receptors in mediation of the toxic effects of cocaine was studied in male ICR mice. Cocaine HCl (90 mg/kg, IP) induced seizures in 95% and death within 24 h in 68% (n = 135) of the animals. There was a significant correlation (r = .54) between the time to onset of convulsions and the time to death in mice which died within 30 min of injection (n = 84). Pretreatment with selected EAA receptor antagonists 15 min prior to cocaine differentially blocked cocaine toxicity. Selective N-methyl-D-aspartic acid (NMDA) receptor antagonists (MK-801, dextrorphan, CPP) decreased both the incidence of seizures and mortality. A nonselective EAA antagonist, kynurenic acid, decreased lethality in doses which did not reduce convulsions. A similar action was observed following pretreatment with the selective kainic acid/AMPA receptor antagonist, GDEE. Antagonists at EAA receptors can provide significant protection against cocaine-induced toxicity. Moreover, the data provide evidence for the involvement of both NMDA and non-NMDA receptor subtypes in aspects of cocaine toxicity.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Anticonvulsants; Cocaine; Death; Dextrorphan; Dizocilpine Maleate; Dose-Response Relationship, Drug; Glutamates; Kynurenic Acid; Male; Mice; Mice, Inbred ICR; Piperazines; Quinoxalines; Receptors, Glutamate; Receptors, N-Methyl-D-Aspartate; Receptors, Neurotransmitter; Seizures; Time Factors

GDEE, an antagonist of the AA2 or quisqualic acid category of excitatory amino acid receptor, decreases behavioral activity and locomotor stimulation induced by cocaine and amphetamine when locally injected into the nucleus accumbens. The present experiment was intended to examine the effects of systemic GDEE and other excitatory amino acid antagonists on stimulant-induced locomotor activity. GDEE markedly attenuated the stimulant effect of amphetamine, and partially blocked the effects of phencyclidine (PCP). Apomorphine-induced cage climbing behavior was partially decreased by lower dosages of GDEE, but was almost completely blocked by the highest dosage tested. Amphetamine-induced stimulation of locomotor activity was not decreased by any of the other excitatory amino acid antagonists that were tested, including MK-801, 2-amino-7-phosphonoheptanoic acid (APH), or CNQX. APH decreased stereotypy only at a high dosage (250 mg/kg), which also produces ataxia. Several other compounds, including L-glutamic acid gamma ethyl ester (GMEE), L-glutamic acid, glycine, and L-glutamine did not block amphetamine-induced stimulation in molar dosages equivalent to the highest dosage of GDEE (8 mmol/kg). It is concluded that the AA2 excitatory amino acid receptor is important in the expression of activating effects of stimulant drugs.

Topics: 2-Amino-5-phosphonovalerate; 6-Cyano-7-nitroquinoxaline-2,3-dione; Amino Acids; Amphetamine; Animals; Apomorphine; Behavior, Animal; Central Nervous System Stimulants; Dibenzocycloheptenes; Dizocilpine Maleate; Dose-Response Relationship, Drug; Female; Glutamates; Mice; Motor Activity; Phencyclidine; Quinoxalines; Receptors, Amino Acid; Receptors, Cell Surface; Stereotyped Behavior