Effects of haloperidol-induced dopamine receptor supersensitivity on kindled seizure development.
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.
D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001971:Bromocriptine; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000008:administration & dosage*; D007696:Kindling, Neurologic / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D012640:Seizures / Q000188:drug therapy*; D013134:Spiperone / Q000008:administration & dosage / Q000378:metabolism; D013997:Time Factors
D011954:Receptors, Dopamine; D001971:Bromocriptine; D013134:Spiperone; D006220:Haloperidol