dizocilpine-maleate and Reflex--Abnormal

Potentiation of GABA(A) receptor-mediated inhibitory neurotransmission contributes to the anesthetic action of thiopental. However, the inhibiting action of general anesthetic on excitatory neurotransmission also purportedly underlies its effects. The aim of the study was to elucidate the role of glutamate receptors (NMDA and AMPA receptors) in thiopental-induced anesthesia. Intracerebroventricular (i.c.v.) NMDA (50 ng) significantly increased the induction time of loss of righting reflex and decreased sleep time induced by intraperitoneal injection (i.p.) of thiopental (50 mg/kg). Furthermore, NMDA at 50 ng i.c.v. increased the 50% effective dose values for thiopental to produce loss of righting reflex and immobility in response to noxious tail clamp by 25% and 21% (p < 0.05), respectively. However, intrathecal (IT) administration of NMDA or both of i.c.v. or IT administration of AMPA did not show such antagonizing effects on thiopental action at subconvulsive dose. Finally, thiopental (25 mg/kg i.p.) inhibited convulsions induced by NMDA (0.4 microg i.c.v.) or bicuculline (0.6 microg i.c.v.). However, i.p. muscimol (1 mg/kg) blocked the convulsions induced by bicuculline, but not those induced by NMDA at 3 mg/kg. Similarly, i.p. MK-801 (0.1 mg/kg) antagonized NMDA-induced convulsions, but not bicuculline-induced convulsions at 0.3 mg/kg. Therefore, we suggest that the effects of the selective GABA(A) and NMDA receptors on convulsive behavior are special to their sites of action, and that the inhibitory action of thiopental on NMDA receptors is possibly not mediated by secondary effects of its GABA(A) receptors agonism. These results above indicate the involvement of NMDA receptors in thiopental-induced anesthesia in mice.

Topics: Analgesics; Anesthetics, Intravenous; Animals; Anticonvulsants; Behavior, Animal; Bicuculline; Dizocilpine Maleate; Female; GABA Agonists; GABA Antagonists; GABA-A Receptor Agonists; GABA-A Receptor Antagonists; Male; Mice; Movement; Muscimol; N-Methylaspartate; Pain Measurement; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate; Reflex, Abnormal; Seizures; Thiopental

1. Many processes in mammalian and invertebrate central nervous systems exhibit habituation and/or sensitization of their responses to repetitive stimuli. Here, we studied the adaptive behaviours of the respiratory pattern generator in rat on repetitive vagal-afferent stimulation and compared these behaviours obtained in vivo with the reported effects of such stimuli on synaptic transmission in the corresponding signal pathway in vitro. 2. Sustained (1 min) electrical pulsed stimulation of the vagus nerve elicited the classic Hering-Breuer (HB) reflex slowing of the respiratory rhythm followed by a bi-exponential recovery, and a post-stimulus rebound (PR). The recovery from the HB reflex satisfied the classic criteria of habituation. 3. The fast component of the recovery and the PR were abolished by systemic administration of an NMDA receptor antagonist or electrolytic lesioning of the pontine Kolliker-Fuse nucleus. The characteristics of the fast recovery and PR suggest a vagally induced desensitization of the NMDA receptor-dependent pontine input to the respiratory pattern generator. 4. The slow component of recovery persist after both experimental interventions and accounted for the habituation to the vagal input. The characteristics of the slow recovery in vivo were reminiscent of the reported synaptic accommodation in vitro in the medullary region where vagal afferents terminate. 5. The habituation of vagal input and desensitization of pontine input act in concert to offset the HB reflex. Such simultaneous habituation-desensitization in parallel neural pathways with differing sensitivities to NMDA receptor activation represent a hitherto unknown pairing of dual non-associative learning processes in the mammalian brain.

Topics: Animals; Dizocilpine Maleate; Electric Stimulation; Excitatory Amino Acid Antagonists; Female; Habituation, Psychophysiologic; Male; Memory, Short-Term; Periodicity; Phrenic Nerve; Pons; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Reflex, Abnormal; Respiration; Vagotomy; Vagus Nerve

Spinal cord injury can lead to an exaggeration of transmission through spinal pathways, resulting in muscle spasticity, chronic pain, and abnormal control of blood pressure and bladder function. These conditions are mediated, in part, by N-methyl-D-aspartate (NMDA) receptors on spinal neurons, but the effects of cord injury on the expression or function of these receptors is unknown. Therefore, antibodies to the NMDA-R1 receptor subunit and binding of [3H]MK-801 were used to assess NMDA receptors in the spinal cord. Receptor density in rats with intact spinal cords was compared to that in rats 1 and 2 weeks after spinal cord transection (SCT) at the mid-thoracic level. At 1 and 2 weeks after SCT, [3H]MK-801 binding was reduced in most laminae in cord segments caudal to the injury, whereas no decrease in amount of R1 subunit immunoreactivity was observed. No significant changes in [3H]MK-801 binding and NMDA-R1 immunoreactivity could be seen rostral to the transection. Since [3H]MK-801 binding requires an open ion channel, the discrepancy between [3H]MK-801 binding and immunocytochemistry may indicate a loss of functional receptors without a consistent change in their total number. Therefore, the exaggerated reflexes that are well established in rats 2 weeks after cord injury must be mediated by a mechanism that withstands attenuation of NMDA receptor function.

Topics: Animals; Autonomic Nervous System Diseases; Autoradiography; Chronic Disease; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Immunohistochemistry; Male; Muscle Spasticity; Nociceptors; Pain; Radioligand Assay; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Reflex, Abnormal; Spinal Cord; Spinal Cord Injuries; Tritium