Brain research bulletin
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Brain research bulletin · Oct 2002
Protective effect of the antiepileptic drug candidate talampanel against AMPA-induced striatal neurotoxicity in neonatal rats.
2,3-Benzodiazepines represent a family of specific, noncompetitive AMPA receptor antagonists with anticonvulsant and neuroprotective properties. In this study, the antiexcitotoxic potency of the clinical antiepileptic drug candidate, talampanel (4 x 2 mg/kg), and that of two related 2,3-benzodiazepines, 5-(4-aminophenyl)-8-methyl-9H-1,3-dioxolo[4,5-h][2,3]-benzodiazepine (GYKI 52466) (4 x 10 mg/kg) and GYKI 53784 (4 x 2 mg/kg), was investigated in 7-day-old rats. The AMPA antagonists were applied in four consecutive i.p. injections at 1-h intervals, the first dosage was given shortly after the intrastriatal injection of (S)-alpha-amino-3-hydroxy-5,7-methylisoxazole-4-propionic acid (AMPA) (2.5 nmol). ⋯ Furthermore, the three compounds attenuated the unilateral AMPA injection-induced turning behavior and seizure-like events. Our present findings are in agreement with those of other investigators who found talampanel neuroprotective in various in vivo experimental models. These data indicate that besides being a promising antiepileptic drug candidate talampanel may have a value in the pharmacotherapy of acute and chronic neurodegenerative diseases, including perinatal ischemia/hypoxia-induced brain injuries, as well.
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Brain research bulletin · Sep 2002
Comparative StudyDifferential effect of peripheral glutamate (NMDA, non-NMDA) receptor antagonists on bee venom-induced spontaneous nociception and sensitization.
This study aimed to investigate the role of peripheral N-methyl-d-aspartate (NMDA) and non-NMDA receptor on (1). spontaneous nociception and (2). on sensitization induced by subcutaneous (s.c.) injection of bee venom (0.2mg/50 micro l) in rats. Peripheral s.c. administration of the competitive NMDA receptor antagonist dl-2-amino-5-phosphonovaleric acid (AP5), the non-competitive NMDA receptor channel blocker MK-801, and the competitive non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were performed before (pre-treatment) and after (post-treatment) bee venom-induced inflammation. Pre-treatment with AP5 (10mM, 50 micro l) and both pre-treatment and post-treatment with MK-801 (2mM, 50 micro l) into the same area of the bee venom injection site markedly reduced the bee venom-increased spontaneous responses of wide-dynamic range (WDR) neuron of the spinal cord. ⋯ Additionally, the role of peripheral NMDA and non-NMDA receptors on bee venom-induced mechanical allodynia and hyperalgesia were investigated and assessed by the paw withdrawal reflex to the innocuous and noxious mechanical stimulation. Peripheral administration of AP5, but not CNQX, reduced mechanical allodynia and hyperalgesia. The data suggest that the peripheral NMDA receptor, but not non-NMDA receptor, plays a pivotal role in the bee venom-induced persistent nociception and hyperexcitability.
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Brain research bulletin · Sep 2002
Origins of GABA(B) receptor-like immunoreactive terminals in the rat spinal dorsal horn.
By means of immunohistochemistry for gamma-aminobutyric acid receptor B subtype (GABA(B)R), the origins of GABA(B)R-like immunoreactive (GABA(B)R-LI) terminals in the rat spinal dorsal horn were investigated. After dorsal root rhizotomy and/or spinal cord hemisection, the densities of GABA(B)R-LI terminals were remarkably depleted in the ipsilateral superficial dorsal horn of relevant segments, whereas GABA(B)R-LI neurons and sparsely distributed GABA(B)R-LI terminals remained. After injection of Fluoro-Gold (FG) into the left side of superficial lumbar dorsal horn, FG retrograde-labeled neurons were mainly observed in the ipsilateral rostral ventromedial medulla (RVM) and brainstem raphe nuclei. ⋯ Additionally, immunofluorescence histochemical double-staining revealed that the majority of GABA(B)R-LI neurons in the periaqueductal gray (PAG), RVM and brainstem raphe nuclei showed 5-hydroxytryptamine (5-HT)-like immunoreactivity. The present study morphologically proves that GABA(B)R-LI terminals in the spinal dorsal horn originate from peripheral afferents, intrinsic neurons and supraspinal structures; GABA(B)R and 5-HT co-exist in many neurons in the PAG, RVM and brainstem raphe nuclei. Considering that PAG, RVM, brainstem raphe nuclei and spinal dorsal horn are important structures involved in the pain modulation, we suggest that the descending pain modulation system might be mediated, at least in part, by GABA(B)R.
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Brain research bulletin · Jun 2002
Comparative StudyWithdrawal from dependence upon butorphanol uniquely increases kappa(1)-opioid receptor binding in the rat brain.
Changes in kappa(1)-opioid receptor binding have been implicated in the development of dependence upon and withdrawal from butorphanol. Autoradiographic characterization of binding for brain kappa(1)-([3H]CI-977), mu-([3H]DAMGO), and delta-([3H]DPDPE) opioid receptors was performed in rats undergoing naloxone-precipitated withdrawal from dependence upon butorphanol or morphine. Dependence was induced by a 72h i.c.v. infusion with either butorphanol or morphine (26nmol/microl/h). ⋯ During withdrawal from butorphanol, but not morphine, kappa(1)-opioid receptor binding was increased significantly in the frontal cortex, posterior basolateral amygdaloid nucleus, dorsomedial hypothalamus, hippocampus, posterior paraventricular thalamic nucleus, ventral tegmental area and locus coeruleus. In contrast, mu-opioid receptor binding decreased in these brain regions in naloxone-precipitated withdrawal from morphine, but not butorphanol, while binding for delta-opioid receptors was altered in both withdrawal groups. The brain kappa(1)-opioid receptor appears to be more directly involved in the development of physical dependence upon, and the expression of withdrawal from, butorphanol, as opposed to the prototypical opioid analgesic, morphine.
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Brain research bulletin · Jun 2002
Neuropathic pain is associated with alterations of nitric oxide synthase immunoreactivity and catalytic activity in dorsal root ganglia and spinal dorsal horn.
Previous experiments have suggested that nitric oxide may play an important role in nociceptive transmission in the spinal cord. To assess the possible roles of neuronal nitric oxide synthase (nNOS) in spinal sensitization after nerve injury, we examined the distribution of nNOS immunoreactivity in dorsal root ganglia (DRGs) and dorsal horn of the corresponding spinal segments. NOS catalytic activity was also determined by monitoring the conversion of [3H]arginine to [3H]citrulline in the lumbar (L4-L6) spinal cord segments and DRGs in rats 21 days after unilateral loose ligation of the sciatic nerve. ⋯ The alterations of NOS catalytic activity in the spinal segments L4-L6 and corresponding DRGs closely correlated with nNOS distribution detected by immunocytochemistry. No such changes were detected in the contralateral DRGs or spinal cord of sham-operated rats. The results indicate that marked alterations of nNOS in the DRG cells and in the spinal cord may contribute to spinal sensory processing as well as to the development of neuronal plasticity phenomena in the dorsal horn.