+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Excitatory neurotransmission within substantia nigra pars reticulata regulates threshold for seizures produced by pilocarpine in rats: effects of intranigral 2-amino-7-phosphonoheptanoate and N-methyl-D-aspartate



Excitatory neurotransmission within substantia nigra pars reticulata regulates threshold for seizures produced by pilocarpine in rats: effects of intranigral 2-amino-7-phosphonoheptanoate and N-methyl-D-aspartate



Neuroscience 18(1): 61-77



Seizures produced by pilocarpine given i.p. to rats provide an animal model for studying the initiation, spread and generalisation of convulsive activity within the forebrain. Pilocarpine, 380 mg/kg, produces a sequence of behavioural and electroencephalographic alterations indicative of motor limbic seizures and status epilepticus, which is followed by widespread damage to the limbic forebrain resembling that occurring subsequent to prolonged intractable seizures. Microinjections of a selective antagonist at the N-methyl-D-aspartate receptor, (+/-)-2-amino-7-phosphonoheptanoate, into the substantia nigra pars reticulata, bilaterally, protects against the behavioural, electrographic and morphological features of seizures produced by pilocarpine, 380 mg/kg, with an ED50 of 0.0007 mumol (0.0004-0.0011). Microinjections of (+/-)-2-amino-7-phosphonoheptanoate, 0.005 or 0.01 mumol, into the substantia nigra pars compacta or into the dorsal part of mid-anterior striatum do not modify the electrographic and morphological sequelae of pilocarpine, 380 mg/kg. In rats pretreated with microinjections of N-methyl-D-aspartate into the substantia nigra pars reticulata, a non-convulsive dose of pilocarpine, 100 mg/kg, results in recurrent motor limbic seizures and status epilepticus. The ED50 of N-methyl-D-aspartate for the generation of seizures after pilocarpine, 100 mg/kg, is 0.0014 mumol (0.001-0.0019). Electrographic monitoring shows a pattern and sequence of evolution of convulsant activity within the hippocampus and cortex similar to that produced with pilocarpine, 380 mg/kg, alone. Morphological examination of brains from rats treated with N-methyl-D-aspartate in the substantia nigra pars reticulata and subsequently given pilocarpine, 100 mg/kg, which underwent status epilepticus, reveals widespread damage to the amygdala, thalamus, olfactory cortex, substantia nigra, neocortex, and hippocampus. Microinjections of N-methyl-D-aspartate, 0.002 mumol, into either the substantia nigra pars compacta or dorsal striatum, bilaterally, do not augment seizures produced by pilocarpine, 100 mg/kg. The results indicate that the threshold for pilocarpine-induced seizures in rats is modulated by excitatory amino acid neurotransmission within the substantia nigra pars reticulata.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 040086916

Download citation: RISBibTeXText

PMID: 3016600

DOI: 10.1016/0306-4522(86)90179-x


Related references

Effect of intranigral 2 amino 7 phosphonoheptanoate and n methyl d aspartate on seizures produced by pilocarpine in rats. British Journal of Pharmacology 85(Suppl.): 367P, 1985

The effects of N-methyl-D-aspartate antagonist 2-amino-7-phosphonoheptanoic acid microinfusions into the adult male rat substantia nigra pars reticulata are site-specific. Neuroscience Letters 316(2): 108-110, 2001

Cannabinoids inhibit excitatory neurotransmission in the substantia nigra pars reticulata. Neuroscience 97(1): 89-97, 2000

Regulation of substantia nigra pars reticulata neuronal activity by excitatory amino acids. Naunyn-Schmiedeberg's Archives of Pharmacology 360(4): 402-412, 1999

Nitrous oxide reverses the increase in striatal dopamine release produced by N-methyl-D-aspartate infusion in the substantia nigra pars compacta in rats. Neuroscience Letters 343(2): 147-149, 2003

Striatonigral lesions and intranigral injection of receptor inactivator eedq prevent d 1 agonist effects on substantia nigra pars reticulata snpr neurons. Society for Neuroscience Abstracts 15(1): 428, 1989

Metabolic perturbation in the substantia nigra pars reticulata during flurothyl induced seizures in rats. Physiologia Bohemoslovaca 34(5): 416-417, 1985

Different effects of morphine in substantia nigra pars compacta and pars reticulata on motility of rats. Neuroscience Letters (Suppl. 10): S491, 1982

Electrical stimulation of the substantia nigra pars reticulata (SNr) suppresses chemically induced neocortical seizures in rats. Journal of Molecular Neuroscience 53(4): 546-552, 2014

Site-specific effects of local pH changes in the substantia nigra pars reticulata on flurothyl-induced seizures. Brain Research 782(1-2): 310-313, 1998

Immunohistochemical localization of N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor subunits in the substantia nigra pars compacta of the rat. Neuroscience 89(1): 209-220, 1999

Analysis of the effect of cannabinoids on GABAergic neurotransmission in the substantia nigra pars reticulata. Naunyn-Schmiedeberg's Archives of Pharmacology 365(4): 326-334, 2002