Taste responses in the parabrachial nucleus (PBN) are significantly affected by stimulation or lesion of the central nucleus of the amygdala (CeA). To examine if the glutamate receptors in the CeA are involved in this modulation, the effects of microinjection of 6-cyano-7-nitro-quinoxaline-2, 3-dione (CNQX), an AMPA receptor antagonist, into the CeA on the activities of PBN taste neurons were observed by using extracellular recording technique. Responses of PBN taste neurons to taste stimuli were observed before and after CNQX administered to the CeA. In general, drug administration produced a time-dependent suppress of the responses in 30% PBN taste neurons, with the firing rates to HCl and QHCl were significantly lowered (P<0.05). According to the best-stimulus category, 40% NaCl-best (6/15), 30% HCl-best (3/10) and 20% QHCl-best (1/5) neurons decreased their responses to at least one basic taste stimulus after CNQX injection. In HCl- and QHCl-best neurons, the main responses were significantly inhibited after drug injections (P<0.01). The correlation coefficient of responses between the NaCl and the other three tastants decreased after drug administration to the CeA. These results suggest that AMPA receptors within the CeA may be involved in the descending modulation in the PBN taste neurons.
6-Cyano-7-nitroquinoxaline-2,3-dione ; pharmacology ; Amygdala ; drug effects ; physiology ; Animals ; Electric Stimulation ; methods ; Evoked Potentials ; physiology ; Male ; Microinjections ; Pons ; physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA ; antagonists & inhibitors ; Taste ; physiology ; Taste Threshold

OBJECTIVETo explore the effects of exposure to aluminum (Al) on long-term potentiation (LTP) and AMPA receptor subunits in rats in vivo.

METHODSDifferent dosages of aluminum-maltolate complex [Al(mal)3] were given to rats via acute intracerebroventricular (i.c.v.) injection and subchronic intraperitoneal (i.p.) injection. Following Al exposure, the hippocampal LTP were recorded by field potentiation technique in vivo and the expression of AMPAR subunit proteins (GluR1 and GluR2) in both total and membrane-enriched extracts from the CA1 area of rat hippocampus were detected by Western blot assay.

RESULTSAcute Al treatment produced dose-dependent suppression of LTP in the rat hippocampus and dose-dependent decreases of GluR1 and GluR2 in membrane extracts; however, no similar changes were found in the total cell extracts, which suggests decreased trafficking of AMPA receptor subunits from intracellular pools to synaptic sites in the hippocampus. The dose-dependent suppressive effects on LTP and the expression of AMPA receptor subunits both in the membrane and in total extracts were found after subchronic Al treatment, indicating a decrease in AMPA receptor subunit trafficking from intracellular pools to synaptic sites and an additional reduction in the expression of the subunits.

CONCLUSIONAl(mal)3 obviously and dose-dependently suppressed LTP in the rat hippocampal CA1 region in vivo, and this suppression may be related to both trafficking and decreases in the expression of AMPA receptor subunit proteins. However, the mechanisms underlying these observations need further investigation.

Aluminum ; toxicity ; Animals ; Down-Regulation ; drug effects ; genetics ; physiology ; Hippocampus ; drug effects ; physiology ; Long-Term Potentiation ; drug effects ; genetics ; physiology ; Male ; Protein Transport ; drug effects ; genetics ; physiology ; Random Allocation ; Rats ; Receptors, AMPA ; antagonists & inhibitors ; genetics ; metabolism ; Toxicity Tests, Acute ; Toxicity Tests, Subchronic

Antagonists for spinal N-methyl-D-aspartate (NMDA) and amino-hydroxy-methtyl-isoxazolepropionate (AMPA) receptors are effective in attenuating acute nociception or injury-induced hyperalgesia. The antinociception of spinal gabapentin is developed in injury-induced hyperalgesia without affecting acute nociception. The authors evaluated the effects of intrathecal gabapentin, NMDA antagonist (MK801) and AMPA antagonist (NBQX) in the formalin test which shows injury-induced hyperalgesia as well as acute pain. We further assessed the interactions between gabapentin and either MK801 or NBQX. Male Sprague-Dawley rats were implanted with intrathecal catheters. To evoke pain, 50 microliter of 5% formalin solution was injected into the hindpaw. The interaction was investigated by a fixed dose analysis or an isobolographic analysis. MK801 and NBQX suppressed flinching responses during phase 1 of the formalin test, while gabapentin had little effect on phase 1. All three agents decreased the phase 2 flinching response. A fixed dose analysis in phase 1 showed that gabapentin potentiated the antinociceptive effect of MK801 and NBQX. Isobolographic analysis in phase 2 revealed a synergistic interaction after coadministration of gabapentin-MK801 or gabapentin-NBQX. Correspondingly, spinal gabapentin with NMDA or AMPA antagonist may be useful in managing acute pain and injury-induced hyperalgesia.
Amines/administration & dosage/*pharmacology ; Analgesics/*pharmacology ; Animals ; Cyclohexanecarboxylic Acids/administration & dosage/*pharmacology ; Dizocilpine Maleate/*pharmacology ; Drug Interactions ; Excitatory Amino Acid Antagonists/*pharmacology ; Hyperalgesia/drug therapy ; Injections, Spinal ; Male ; Quinoxalines/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA/drug effects/physiology ; Receptors, N-Methyl-D-Aspartate/drug effects/physiology ; Research Support, Non-U.S. Gov't ; gamma-Aminobutyric Acid/administration & dosage/*pharmacology