Role of dopamine D-1 and D-2 antagonists in a model of focal epilepsy induced by electrical stimulation of hippocampus and amygdala in the rabbit

Bo, Paola; Soragna, Debora; Marchioni, Enrico; Candeloro, Elisa; Albergati, Andrea; Savoldi, F

doi:10.1016/0278-5846(95)00120-k

Cited by 14 publications

(11 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most probably, D1‐like receptors and modifications of GABAergic and glutamatergic synapses are essential for the proconvulsive effect of high dopamine concentrations, but the pharmacology of the anticonvulsive effect is less clear. This study shows, to our knowledge for the first time, that dopamine can mediate pro‐ and anticonvulsive effects in the immature hippocampus, in accordance with a variety of studies that demonstrate pro‐ and anticonvulsive effects of dopamine in the adult hippocampus (Haas et al,1984; Suppes et al,1985; Bo et al,1995). It has been proposed that dopamine plays an essential role in controlling the functional state of the mature hippocampus (Jay,2003).…”

Section: Discussionsupporting

confidence: 91%

Dopaminergic modulation of low‐Mg²⁺‐induced epileptiform activity in the intact hippocampus of the newborn mouse in vitro

Sharopov

Moser

Chen

et al. 2012

J of Neuroscience Research

View full text Add to dashboard Cite

To investigate whether epileptiform activity in the immature brain is modulated by dopamine, we examined the effects of dopaminergic agonists and antagonists in an intact in vitro preparation of the isolated corticohippocampal formation of immature (postnatal days 3 and 4) C57/Bl6 mice using field potential recordings from CA3. Epileptiform discharges were induced by a reduction of the extracellular Mg(2+) concentration to 0.2 mM. These experiments revealed that low concentrations of dopamine (<0.3 μM) attenuated epileptiform activity, whereas >3 μM dopamine enhanced epileptiform activity. The D1-agonist SKF38393 (10 μM) had a strong proconvulsive effect, and the D2-like agonist quinpirole (10 μM) mediated a weak anticonvulsive effect. The proconvulsive effect of 10 μM dopamine was completely abolished by the D1-like receptor antagonist SCH39166 (2 μM) or the D2-like antagonist sulpiride (10 μM), whereas the D2 antagonist L-741626 (50 nM) and the D3 antagonist SB-277011-A (0.1 μM) were without effect. The anticonvulsive effect of 0.1 μM dopamine could be suppressed by D1-like, D2, or D3 receptor antagonists. A proconvulsive effect of 10 μM dopamine was also observed when AMPA, NMDA, or GABA(A) receptors were blocked. In summary, these results suggest that 1) dopamine influences epileptiform activity already at early developmental stages; 2) dopamine can bidirectionally influence the excitability; 3) D1-like receptors mediate the proconvulsive effect of high dopamine concentrations, although the pharmacology of the anticonvulsive effect is less clear; and 4) dopamine-induced alterations in GABAergic and glutamatergic systems may contribute to this effect.

show abstract

Section: Discussionsupporting

confidence: 91%

Dopaminergic modulation of low‐Mg²⁺‐induced epileptiform activity in the intact hippocampus of the newborn mouse in vitro

Sharopov

Moser

Chen

et al. 2012

J of Neuroscience Research

View full text Add to dashboard Cite

show abstract

“…In agreement, it has been shown that homocysteine combined with kainate enhances kainate-induced neurotoxicity (Kruman et al 2000). The homocysteine exacerbation of pilocarpine-induced neuronal damage could maybe involve also a contribution of the negative allosteric modulatory action of homocysteine at D2 receptors (Agnati et al 2006;Agnati et al 2008), in view of the neuroprotective role of these receptors (Bo et al 1995;Bozzi et al 2000;Bozzi and Borrelli 2006).…”

Section: Discussionmentioning

confidence: 78%

Homocysteine Potentiates Seizures and Cell Loss Induced by Pilocarpine Treatment

et al. 2009

View full text Add to dashboard Cite

Patients affected by recurrent seizures frequently present increased homocysteine plasma levels in consequence of treatment with antiepileptic drugs. Homocysteine is proconvulsant and can affect the response to antiepileptic drugs. In addition, high homocysteine plasma levels represent a risk factor for cardiovascular and neurodegenerative diseases. To better define the role of increased homocysteine in epilepsy, we analyzed the effects of homocysteine pretreatment in the pilocarpine model of status epilepticus (SE), which is used to mimic temporal lobe epilepsy (TLE) in rodents. Precisely, we investigated whether a moderate hyperhomocysteinemia, unable to cause seizures, could sensitize rats to pilocarpine and cooperate in inducing brain lesions. We found that a subthreshold dose of pilocarpine (200 mg/kg) is sufficient to induce SE in the majority (approximately 90%) of rats pretreated with homocysteine for 2 weeks, whereas only 40% of saline-treated controls developed SE following the same pilocarpine dose. Furthermore, homocysteine pretreatment led to a significant increase in neuronal cell loss evaluated by counting toluidine blue-stained or Fluoro-Jade-positive cells in hippocampal and parahippocampal regions. Pilocarpine augmented amyloid beta expression in both animal groups. However, pretreatment with homocysteine favored the intraneuronal fibrillar conformation of amyloid beta, thus promoting neurodegeneration. These findings indicate that increased homocysteine levels enhance seizure activity and neurodegeneration in pilocarpine-treated rats and suggest that similar detrimental effects may occur in patients affected by TLE.

show abstract

“…By contrast, acepromazine prevented the mortality and eradicated the cardiac instability associated with lithium-pilocarpine seizures in rats (Harrigan et al, 1994). Haloperidol (1 mgkg) significantly increased the afterdischarges evoked by focal electrical stimulation of the rabbit's hippocampus or amygdala (Bo et al, 1995). The same dose of haloperidol also completely blocked the suppressive effect of nigral stimulation on penicillininduced focal hippocampal epilepsy in the cat, although it did not enhance hippocampal spiking by itself (Le Grutta and Sabatino, 1990).…”

Section: Unselective Dopamine Antagonistsmentioning

confidence: 99%

The role of dopamine in epilepsy

Starr

1996

Synapse

241

157

View full text Add to dashboard Cite

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.

show abstract

Role of dopamine D-1 and D-2 antagonists in a model of focal epilepsy induced by electrical stimulation of hippocampus and amygdala in the rabbit

Cited by 14 publications

References 32 publications

Dopaminergic modulation of low‐Mg²⁺‐induced epileptiform activity in the intact hippocampus of the newborn mouse in vitro

Dopaminergic modulation of low‐Mg²⁺‐induced epileptiform activity in the intact hippocampus of the newborn mouse in vitro

Homocysteine Potentiates Seizures and Cell Loss Induced by Pilocarpine Treatment

The role of dopamine in epilepsy

Contact Info

Product

Resources

About

Role of dopamine D-1 and D-2 antagonists in a model of focal epilepsy induced by electrical stimulation of hippocampus and amygdala in the rabbit

Cited by 14 publications

References 32 publications

Dopaminergic modulation of low‐Mg2+‐induced epileptiform activity in the intact hippocampus of the newborn mouse in vitro

Dopaminergic modulation of low‐Mg2+‐induced epileptiform activity in the intact hippocampus of the newborn mouse in vitro

Homocysteine Potentiates Seizures and Cell Loss Induced by Pilocarpine Treatment

The role of dopamine in epilepsy

Contact Info

Product

Resources

About

Dopaminergic modulation of low‐Mg²⁺‐induced epileptiform activity in the intact hippocampus of the newborn mouse in vitro

Dopaminergic modulation of low‐Mg²⁺‐induced epileptiform activity in the intact hippocampus of the newborn mouse in vitro