Effect of increments in the concentration of dopamine in the central nervous system on audiogenic seizures in DBA/2J mice

Dailey, John W.; Jobe, P C

doi:10.1016/0028-3908(84)90123-0

Cited by 19 publications

(3 citation statements)

References 31 publications

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“…However, it is not clear whether increased dopamine levels play a role in causing convulsions or in counteracting convulsions in cyanide-infused rats. Administration of L-DOPA gives a dramatic decrease in the incidence of extensor seizures (Dailey & Jobe 1984;Maynert 1969), why convulsions could hardly be provoked by increased dopamine levels. Since increased dop-amine levels did not cause the convulsions, other possible mechanisms must be considered.…”

Section: Discussionmentioning

confidence: 99%

Estimation of the Convulsive Effect of Cyanide in Rats

Cassel

1995

Pharmacology & Toxicology

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Convulsions are frequently observed in severe, acute cyanide intoxication. The mechanisms involved are not well known. In the present study, the convulsive effect of cyanide was examined in the rat by means of a dose threshold determination after infusion of cyanide. An optimal dose rate of 1.80 mg/min./kg was determined. By infusing this optimal dose rate it was possible to divide another cyanide-treated group of rats into two groups: one without and another with convulsions. After the experiment all animals were killed by exposure to high intensity microwave irradiation. Regional dopamine, noradrenaline and main dopamine metabolites were isolated and analyzed using high pressure liquid chromatography and electrochemical detection. Striatal noradrenaline was decreased but dopamine and its metabolites were increased in rats infused with cyanide at the optimal dose rate until the convulsions started. Animals infused with the threshold dose at the optimal dose rate did not show any significant changes in noradrenaline or in dopamine metabolites, but all animals showing convulsions also had increased striatal dopamine levels. Thus changes in dopamine appear to be dependent on convulsions.

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Section: Discussionmentioning

confidence: 99%

Estimation of the Convulsive Effect of Cyanide in Rats

Cassel

1995

Pharmacology & Toxicology

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“…The inhibition of adenosine metabolism by pretreatment with 5-iodotubercidin (5-ITU) increased the susceptibility to S-IRA of DBA/2 mice, which initially displayed only AGSs, indicating that excessive adenosine signaling may contribute to seizure-induced death in these mice ( 28 ). Reduced brain levels of NE and DA are also responsible for increased AGS susceptibility ( 51 ). Generally, DBA/2 mice show lower levels of NE and DA in the brain than C57BL/6J mice; the administration of Levodopa (L-DOPA) was found to attenuate AGS in DBA/2 mice by increasing the brain levels of these neurotransmitters, particularly DA, which is the active principle formed from L-DOPA ( 51 , 70 ).…”

Section: Alteration Of Neurotransmissions In Dba/2 Micementioning

confidence: 99%

“…Reduced brain levels of NE and DA are also responsible for increased AGS susceptibility ( 51 ). Generally, DBA/2 mice show lower levels of NE and DA in the brain than C57BL/6J mice; the administration of Levodopa (L-DOPA) was found to attenuate AGS in DBA/2 mice by increasing the brain levels of these neurotransmitters, particularly DA, which is the active principle formed from L-DOPA ( 51 , 70 ).…”

Section: Alteration Of Neurotransmissions In Dba/2 Micementioning

confidence: 99%

Audiogenic epileptic DBA/2 mice strain as a model of genetic reflex seizures and SUDEP

Bosco,

Guarnieri,

Leo

et al. 2023

Front. Neurol.

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Epilepsy is a chronic neurological disease characterized by abnormal brain activity, which results in repeated spontaneous seizures. Sudden unexpected death in epilepsy (SUDEP) is the leading cause of seizure-related premature death, particularly in drug-resistant epilepsy patients. The etiology of SUDEP is a structural injury to the brain that is not fully understood, but it is frequently associated with poorly controlled and repeated generalized tonic–clonic seizures (GTCSs) that cause cardiorespiratory and autonomic dysfunctions, indicating the involvement of the brainstem. Both respiratory and cardiac abnormalities have been observed in SUDEP, but not much progress has been made in their prevention. Owing to the complexity of SUDEP, experimental animal models have been used to investigate cardiac and/or respiratory dysregulation due to or associated with epileptic seizures that may contribute to death in humans. Numerous rodent models, especially mouse models, have been developed to better understand epilepsy and SUDEP physiopathology. This review synthesizes the current knowledge about dilute brown agouti coat color (DBA/2) mice as a possible SUDEP model because respiratory arrest (RA) and sudden death induced by audiogenic generalized seizures (AGSs) have been observed in these animals. Respiratory/cardiac dysfunction, brainstem arousal system dysfunction, and alteration of the neurotransmitter systems, which are observed in human SUDEP, have also been observed in these mice. In particular, serotonin (5-HT) alteration and adenosine neurotransmission appear to contribute to not only the pathophysiological mechanisms of medication but also seizure-related respiratory dysfunctions in this animal model. These neurotransmitter systems could be the relevant targets for medication development for chronic epilepsy and SUDEP prevention. We reviewed data on AGSs in DBA/2 mice and the relevance of this model of generalized tonic–clonic epilepsy to human SUDEP. Furthermore, the advantages of using this strain prone to AGSs for the identification of possible new therapeutic targets and treatment options have also been assessed.

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The role of dopamine in epilepsy

Starr

1996

Synapse

240

157

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The clinical benefits of dopamine agonists in the management of epilepsy can be traced back over a century, whilst the introduction of neuroleptics into psychiatry practice 40 years ago witnessed the emergence of fits as a side effect of dopamine receptor blockade. Epidemiologists noticed a reciprocal relationship between the supposed dopaminergic overactivity syndrome of schizophrenia and epilepsy, which came to be regarded as a dopamine underactivity condition. Early pharmacological studies of epilepsy employed nonselective drugs, that often did not permit dopamine's antiepileptic action to be clearly dissociated from that of other monoamines. Likewise, the biochemical search for genetic abnormalities in brain dopamine function, as predeterminants of spontaneous epilepsy, proved largely inconclusive. The discovery of multiple dopamine receptor families (D1 and D2), mediating opposing influences on neuronal excitability, heralded a new era of dopamine‐epilepsy research. The traditional anticonvulsant action of dopamine was attributed to D2 receptor stimulation in the forebrain, while the advent of selective D1 agonists with proconvulsant properties revealed for the first time that dopamine could also lower the seizure threshold from the midbrain. Whilst there is no immediate prospect of developing D2 agonists or D1 antagonists as clinically useful antiepileptics, there is a growing awareness that seizures might be precipitated as a consequence of treating other neurological disorders with D2 antagonists (schizophrenia) or D1 agonists (parkinsonism). © 1996 Wiley‐Liss, Inc.

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Effect of increments in the concentration of dopamine in the central nervous system on audiogenic seizures in DBA/2J mice

Cited by 19 publications

References 31 publications

Estimation of the Convulsive Effect of Cyanide in Rats

Estimation of the Convulsive Effect of Cyanide in Rats

Audiogenic epileptic DBA/2 mice strain as a model of genetic reflex seizures and SUDEP

The role of dopamine in epilepsy

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