Differential changes in induced seizures after hippocampal treatment of rats with an antisense oligodeoxynucleotide to the GABA(A) receptor gamma2 subunit. 1997

J Karle, and P Laudrup, and F Sams-Dodd, and J D Mikkelsen, and M Nielsen
The Research Institute of Biological Psychiatry, St. Hans Hospital, Roskilde, Denmark.

Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the brain. Impairment of GABAergic neurotransmission may be involved in the pathogenesis of epileptic phenomena. We have previously characterized biochemical and histological changes following unilateral intrahippocampal infusion of a phosphorothioate antisense oligodeoxynucleotide to the GABA(A) receptor gamma2 subunit in rats in vivo. The aim of the present study was to investigate the behavioral changes of rats following unilateral hippocampal antisense 'knockdown' of the GABA(A) receptor gamma2 subunit. Antisense, but not mismatch control oligodeoxynucleotide treated rats had a significant weight loss (10%) during 6 d of treatment. Antisense treated rats exhibited no changes in spontaneous behavior, including anxiety-like behavior as measured in the social interaction test, compared to mismatch oligodeoxynucleotide treated rats. However, antisense treated rats developed pronounced changes in induced seizure activity. Seizures induced by subcutaneously injected pentylenetetrazol were markedly accentuated in antisense treated rats compared to treatment naive rats, whereas mismatch treated rats showed a lower seizure score than that of naive rats. Antisense treated rats had a significantly elevated threshold for seizures induced by electrical stimulation in the maximal electroshock seizure threshold test. The results suggest that intrahippocampal infusion of antisense oligodeoxynucleotide to the GABA(A) receptor gamma2 subunit leads to specific alterations in the sensitivity to induced seizures. The results are viewed as consequences of selective down-regulation of GABA(A) receptors and diminished inhibitory neurotransmission in the hippocampus.

UI MeSH Term Description Entries
D007398 Interpersonal Relations The reciprocal interaction of two or more persons. Social Relationships,Husband-Wife Communication,Partner Communication,Communication, Husband-Wife,Communication, Partner,Husband Wife Communication,Husband-Wife Communications,Interpersonal Relation,Partner Communications,Relation, Interpersonal,Relationship, Social,Social Relationship
D008297 Male Males
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D010433 Pentylenetetrazole A pharmaceutical agent that displays activity as a central nervous system and respiratory stimulant. It is considered a non-competitive GAMMA-AMINOBUTYRIC ACID antagonist. Pentylenetetrazole has been used experimentally to study seizure phenomenon and to identify pharmaceuticals that may control seizure susceptibility. Leptazole,Pentamethylenetetrazole,Pentetrazole,Cardiazol,Corasol,Corazol,Corazole,Korazol,Korazole,Metrazol,Metrazole,Pentazol,Pentylenetetrazol
D011963 Receptors, GABA-A Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop. Benzodiazepine-Gaba Receptors,GABA-A Receptors,Receptors, Benzodiazepine,Receptors, Benzodiazepine-GABA,Receptors, Diazepam,Receptors, GABA-Benzodiazepine,Receptors, Muscimol,Benzodiazepine Receptor,Benzodiazepine Receptors,Benzodiazepine-GABA Receptor,Diazepam Receptor,Diazepam Receptors,GABA(A) Receptor,GABA-A Receptor,GABA-A Receptor alpha Subunit,GABA-A Receptor beta Subunit,GABA-A Receptor delta Subunit,GABA-A Receptor epsilon Subunit,GABA-A Receptor gamma Subunit,GABA-A Receptor rho Subunit,GABA-Benzodiazepine Receptor,GABA-Benzodiazepine Receptors,Muscimol Receptor,Muscimol Receptors,delta Subunit, GABA-A Receptor,epsilon Subunit, GABA-A Receptor,gamma-Aminobutyric Acid Subtype A Receptors,Benzodiazepine GABA Receptor,Benzodiazepine Gaba Receptors,GABA A Receptor,GABA A Receptor alpha Subunit,GABA A Receptor beta Subunit,GABA A Receptor delta Subunit,GABA A Receptor epsilon Subunit,GABA A Receptor gamma Subunit,GABA A Receptor rho Subunit,GABA A Receptors,GABA Benzodiazepine Receptor,GABA Benzodiazepine Receptors,Receptor, Benzodiazepine,Receptor, Benzodiazepine-GABA,Receptor, Diazepam,Receptor, GABA-A,Receptor, GABA-Benzodiazepine,Receptor, Muscimol,Receptors, Benzodiazepine GABA,Receptors, GABA A,Receptors, GABA Benzodiazepine,delta Subunit, GABA A Receptor,epsilon Subunit, GABA A Receptor,gamma Aminobutyric Acid Subtype A Receptors
D003292 Convulsants Substances that act in the brain stem or spinal cord to produce tonic or clonic convulsions, often by removing normal inhibitory tone. They were formerly used to stimulate respiration or as antidotes to barbiturate overdose. They are now most commonly used as experimental tools. Convulsant,Convulsant Effect,Convulsant Effects,Effect, Convulsant,Effects, Convulsant
D004597 Electroshock Induction of a stress reaction in experimental subjects by means of an electrical shock; applies to either convulsive or non-convulsive states. Electroconvulsive Shock,Electroconvulsive Shocks,Electroshocks,Shock, Electroconvulsive,Shocks, Electroconvulsive
D006234 Handling, Psychological Physical manipulation of animals and humans to induce a behavioral or other psychological reaction. In experimental psychology, the animal is handled to induce a stress situation or to study the effects of "gentling" or "mothering". Handling (Psychology),Handling, Psychology,Psychological Handling,Psychology Handling
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

Related Publications

J Karle, and P Laudrup, and F Sams-Dodd, and J D Mikkelsen, and M Nielsen
August 1997, Brain research,
J Karle, and P Laudrup, and F Sams-Dodd, and J D Mikkelsen, and M Nielsen
January 2001, Brain research bulletin,
J Karle, and P Laudrup, and F Sams-Dodd, and J D Mikkelsen, and M Nielsen
January 2001, Alcohol and alcoholism (Oxford, Oxfordshire),
J Karle, and P Laudrup, and F Sams-Dodd, and J D Mikkelsen, and M Nielsen
December 1998, Journal of neuroscience research,
J Karle, and P Laudrup, and F Sams-Dodd, and J D Mikkelsen, and M Nielsen
May 2001, Nature genetics,
J Karle, and P Laudrup, and F Sams-Dodd, and J D Mikkelsen, and M Nielsen
December 1999, Metabolic brain disease,
J Karle, and P Laudrup, and F Sams-Dodd, and J D Mikkelsen, and M Nielsen
July 2008, Journal of psychopharmacology (Oxford, England),
J Karle, and P Laudrup, and F Sams-Dodd, and J D Mikkelsen, and M Nielsen
February 2002, American journal of human genetics,
J Karle, and P Laudrup, and F Sams-Dodd, and J D Mikkelsen, and M Nielsen
December 2011, Neurochemical research,
J Karle, and P Laudrup, and F Sams-Dodd, and J D Mikkelsen, and M Nielsen
February 2006, Epilepsia,
Copied contents to your clipboard!