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Effects of haloperidol-induced dopamine receptor supersensitivity on kindled seizure development
Abstract:
By using kindling by repetitive amygdala stimulation as a model of generalized seizure development in the rat, we have shown that dopamine receptor subsensitivity has been shown to occur in selected brain areas after the development of seizures. In the present study, the influence of initially altered dopamine receptor sensitivity on the development of seizures was examined by inducing receptor supersensitivity through chronic haloperidol injection before amygdaloid kindling stimulation. Rats injected with haloperidol (5 mg/kg i.p.) for 18 or 30 days were stimulated in the amygdala daily until full seizures were elicited. Starting 2 days after the last injection, rats treated with 5 mg/kg of haloperidol i.p. required significantly more stimulations than their respective control groups. The slowed rate of seizure development was not significant if the kindling stimuli were initiated 6 days posthaloperidol treatment nor if 10-mg doses of haloperidol were used for 30 days. [3H]Spiroperidol binding assays were performed on tissue from striatum and amygdala-pyriform cortex at various times after drug treatment. Increased receptor binding was observed in striatum and amygdala-pyriform cortex of all haloperidol treatment groups. These observations lend support to the hypothesis that dopamine plays a role in seizure suppression as an increased receptor sensitivity to dopamine delayed kindled seizure development.
Insights
Altering dopamine receptor sensitivity influences seizure development. Inducing dopamine receptor supersensitivity in rats delayed the onset of kindled seizures, suggesting dopamine
Area of Science:
- Neuroscience
- Pharmacology
- Epilepsy Research
Background:
- Repetitive amygdala stimulation in rats (kindling) models generalized seizure development.
- Seizure development is associated with dopamine receptor subsensitivity in specific brain regions.
Purpose of the Study:
- To investigate the impact of pre-existing dopamine receptor sensitivity on seizure development.
- To examine if inducing dopamine receptor supersensitivity prior to kindling affects seizure onset.
Main Methods:
- Rats received chronic haloperidol injections to induce dopamine receptor supersensitivity.
- Amygdaloid kindling stimulation was applied daily until generalized seizures occurred.
- Dopamine receptor binding was assessed using [3H]Spiroperidol in striatum and amygdala-pyriform cortex.
Main Results:
- Rats treated with 5 mg/kg haloperidol for 18 or 30 days required significantly more stimulations to elicit seizures.
- This delay in seizure development was not observed with delayed initiation of kindling or higher haloperidol doses (10 mg/kg for 30 days).
- Increased dopamine receptor binding was confirmed in the striatum and amygdala-pyriform cortex of haloperidol-treated rats.
Conclusions:
- These findings support the hypothesis that dopamine plays a role in seizure suppression.
- Enhanced dopamine receptor sensitivity appears to delay the development of kindled seizures.