Intrathecal blockade of both NMDA and non-NMDA receptors attenuates the exercise pressor reflex in cats

In decerebrate unanesthetized cats we tested the hypothesis that glutamatergic-receptor blockade in the lumbosacral spinal cord attenuated the reflex increases in mean arterial pressure, inspired minute ventilation, and renal sympathetic nerve activity (RSNA) evoked by static contraction of the triceps surae muscles. Blockade of N-methyl-D-aspartate (NMDA) receptors by intrathecal injection of DL-2-amino-5-phosphonovaleric acid had no effect on the initial phase of the pressor, ventilatory, and RSNA responses to contraction but did attenuate the secondary phase of these responses. Subsequent blockade of non-NMDA receptors in the lumbosacral spinal cord by intrathecal injection of 6-cyano-7-nitroquinoxaline-2,3-dione attenuated both the initial phase of the pressor, RSNA, and ventilatory responses to contraction and the secondary phase of these responses. In addition, NMDA-receptor blockade had no effect on the pressor or RSNA responses to tendon stretch, whereas non-NMDA-receptor blockade abolished these responses. We confirmed that our results were not related to the order of the antagonists injected by performing a series of experiments in which a non-NMDA-receptor antagonist was injected first. Our findings suggest that non-NMDA receptors mediate the spinal transmission of the initial and secondary phases of the pressor, RSNA, and ventilatory responses to contraction and tendon stretch. Therefore, non-NMDA receptors in the dorsal horn appear to be involved in the spinal processing of input from mechanoreceptors and metaboreceptors. Our findings also suggest that NMDA receptors mediate the spinal transmission of the secondary phase of the pressor, RSNA, and ventilatory responses to contraction but do not mediate the spinal transmission of the responses to tendon stretch. Therefore, NMDA receptors in the dorsal horn appear to be involved in the spinal processing of input from metaboreceptors.

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NMDA Receptor Blockade and Spinal Cord Ischemia Due to Aortic Crossclamping in the Rat Model

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100041202 ◽

1994 ◽

Vol 21 (3) ◽

pp. 227-232 ◽

Cited By ~ 18

Author(s):

F. Follis ◽

K. Miller ◽

O. U. Scremin ◽

S. Pett ◽

R. Kessler ◽

...

Keyword(s):

Spinal Cord ◽

Nmda Receptor ◽

Brain Research ◽

Spinal Cord Ischemia ◽

Intrathecal Injection ◽

Control Group ◽

Receptor Subtype ◽

Receptor Blockade ◽

Mk 801 ◽

Nmda Receptor Blockade

Abstract:Recent brain research proposes that, during ischemia, synaptically released excitatory amino acid neurotransmitters accumulate at toxic concentrations with ensuing neuronal death. Their action is mediated by the receptor subtype N-methyl-D-aspartate (NMDA). The protective effect of NMDA receptor blockade with intrathecal MgS04 and MK-801 was investigated during spinal cord ischemia induced by aortic occlusion of 12 minutes. Male Sprague-Dawley rats, 250-300g, underwent intrathecal administration of 20 μL of normal saline (SA n = 16), MgS04 1M (MG n = 16), or MK-801, 25 mM solutions (MK n = 16) in a randomized order. After 2 hours, the animals underwent occlusion of the thoracic aorta and subclavian arteries for 12 min. An additional control group (CO n = 16) underwent occlusion for 12 minutes, without intrathecal injection. The animals were scored according to their functional performance (LS = lesion score) each day for four days by a blinded observer. Mean LS were calculated for each group at a given day. Treatment and control groups were not different at day 1 (P = 0.302). Group MG was improved from groups SA (P = < 0.0039) and CO (P = < 0.0048) at day 4. This study demonstrates that although intrathecal NMDA receptor blockade with MgS04 or MK-801 does not prevent paraplegia due to spinal cord ischemia in the rat, it could however influence the rate of recovery after ischemic injury.

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NMDA receptor blockade retards axonal growth in the transected spinal cord

Neuroreport ◽

10.1097/00001756-200410250-00012 ◽

2004 ◽

Vol 15 (15) ◽

pp. 2361-2364 ◽

Cited By ~ 3

Author(s):

Louise M. F. Doyle ◽

Barry L. Roberts

Keyword(s):

Spinal Cord ◽

Nmda Receptor ◽

Axonal Growth ◽

Receptor Blockade ◽

Nmda Receptor Blockade

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Recruitment of GABAA inhibition in rat neocortex is limited and not NMDA dependent

Journal of Neurophysiology ◽

10.1152/jn.1995.74.6.2329 ◽

1995 ◽

Vol 74 (6) ◽

pp. 2329-2335 ◽

Cited By ~ 31

Author(s):

D. S. Ling ◽

L. S. Benardo

Keyword(s):

Nmda Receptor ◽

Nmda Receptors ◽

Pyramidal Neurons ◽

Reversal Potential ◽

Cell Voltage ◽

Receptor Blockade ◽

Gamma Aminobutyric Acid ◽

Postsynaptic Currents ◽

Nmda Receptor Blockade ◽

Layer V

1. The recruitment of evoked fast inhibitory postsynaptic currents (IPSCs) and excitatory postsynaptic currents (EPSCs) was examined using whole cell voltage-clamp recordings from layer V pyramidal neurons in slices of rat somatosensory cortex. Synaptic currents were evoked with graded electrical stimulation to assess the relative activation of IPSCs and EPSCs. Fast GABAA ergic IPSCs were selectively recorded by holding cells at potentials equal to EPSC reversal (approximately 0 mV). EPSCs were likewise isolated by holding cells at IPSC reversal potential (about -75 mV). 2. As stimulus intensities were increased, the magnitude of the postsynaptic currents also increased. Over the range of stimuli applied (2-10 V), EPSCs did not exhibit an upper limit. However, fast gamma-aminobutyric acid-A (GABAA-mediated IPSCs reached a maximum at intensities approximately 2 times threshold. 3. The limit on fast inhibition was unresponsive to alterations in N-methyl-D-aspartate (NMDA)-mediated excitation. Exposure to nominally magnesium-free solutions or to the NMDA antagonist 3-[(RS)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid did not affect the fast IPSC maximum. Shifts in the input-output curves for submaximal activation of IPSCs were seen, which were attributed to polysynaptic excitation. 4.Blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate (non-NMDA) receptors with 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) completely abolished synaptically driven, fast GABAA-mediated inhibition. These findings suggested that neocortical inhibitory cells could be driven exclusively through non-NMDA transmission. 5. By comparison, in hippocampal CA1 pyramidal neurons maximal fast inhibition was sensitive to both NMDA and non-NMDA receptor blockade. 6. The results in neocortex were corroborated by direct intracellular recordings from layer V-VI interneurons. Non-NMDA receptor blockade with CNQX prevented synaptic activation of action potentials in these cells, even during cotreatment with magnesium-free solution. 7. Together, these results suggest that recruitment of GABA(A) ergic IPSCs in neocortex is ultimately driven via glutamatergic afferents arriving at non-NMDA receptors on interneurons. Properties limiting fast inhibition would favor the propagation of enhanced excitatory activity through the neuronal network.

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Selective Suppression of Late Laryngeal Adductor Responses by N-Methyl-d-Aspartate Receptor Blockade in the Cat

Journal of Neurophysiology ◽

10.1152/jn.00595.2001 ◽

2002 ◽

Vol 87 (3) ◽

pp. 1252-1262 ◽

Cited By ~ 14

Author(s):

Ranjinidevi Ambalavanar ◽

Laura Purcell ◽

Marcia Miranda ◽

Frank Evans ◽

Christy L. Ludlow

Keyword(s):

Nmda Receptor ◽

Nmda Receptors ◽

Superior Laryngeal Nerve ◽

Receptor Activation ◽

Laryngeal Nerve ◽

Receptor Blockade ◽

Afferent Stimulation ◽

Afferent Fibers ◽

Nmda Receptor Blockade ◽

Alpha Chloralose

Laryngeal adductor responses to afferent stimulation play a key role in airway protection. Although vital for protection during cough and swallow, these responses also must be centrally controlled to prevent airway obstruction by laryngospasm during prolonged stimulation. Our purpose was to determine the role of N-methyl-d-aspartate (NMDA) receptors in modulating early R1 responses (at 9 ms) and/or later more prolonged R2 responses (at 36 ms) during electrical stimulation of the laryngeal afferent fibers contained in the internal branch of the superior laryngeal nerve in the cat. The percent occurrence, amplitude, and conditioning of muscle responses to single superior laryngeal nerve (SLN) stimuli presented in pairs at interstimulus intervals of 250 ms were measured in three experiments: 1) animals that had ketamine as anesthetic premedication were compared with those who did not, when both were maintained under alpha-chloralose anesthesia. 2) The effects of administering ketamine in one group of animals were compared with increasing the depth of alpha-chloralose anesthesia without NMDA receptor blockade in another group of animals. 3) The effects of dextromethorphan (without anesthetic effects) were examined in another group of animals. In the first experiment, the occurrence of R2 responses were reduced from 95% in animals without ketamine premedication to 25% in animals with ketamine premedication ( P = 0.015). No differences occurred in the occurrence, amplitude, latency, or conditioning effects on R1 responses between these groups. In the second experiment, the occurrence of R2 responses was reduced from 96 to 79% after an increase in the depth of anesthesia with alpha-chloralose in contrast with reductions in R2 occurrence from 98 to 19% following the administration of ketamine to induce NMDA receptor blockade along with increased anesthesia ( P = 0.025). In the third experiment, R2 occurrence was reduced from 89 to 27% ( P = 0.017) with administration of dextromethorphan while R1 response occurrence and amplitude did not change. In each of these experiments, NMDA receptor blockade did not have significant effects on cardiac or respiratory rates in any of the animals. The results demonstrate that NMDA receptors play an essential role in long latency R2 laryngeal responses to laryngeal afferent stimulation. On the other hand, early R1 laryngeal adductor responses are likely to involve non-NMDA receptor activation.

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