Adaptive changes in the effects of angiotensin II on the convulsive-seizure threshold in cases of altered sensitivity of dopamine receptors.

The adaptive changes in the effects of the neuropeptide angiotensin II (AT II) on the convulsive-seizure threshold were studied. AT II was injected intracerebroventricularly (i.c.v.) at a dose of 1 micrograms/mouse and convulsive seizures were induced by timed intravenous infusion of pentylenetetrazol (PTZ) in male albino mice. The sensitivity of DA receptors was altered by: repeated (14 days) intraperitoneal (i.p.) injection of the DA receptor antagonist pimozide (1 mg.kg-1) and subsequent withdrawal of the antagonist for 7 or 21 days; and repeated (14 days) subcutaneous (s.c.) injection of the DA receptor agonist apomorphine (0.5 mg.kg-1). The convulsive-seizure-increasing effect of AT II was enhanced after multiple administration of pimozide and particularly after its withdrawal for 21 days. This effect was also enhanced though to a lesser degree by repeated treatment with apomorphine. Apomorphine applied 21 days after withdrawal of pimozide decreased the pimozide-enhanced effect of AT II. All these adaptive changes in the effects of AT II on the PTZ convulsive-seizure threshold might be associated with the altered receptor-receptor (AT II-DA-GABA) interactions in the brain structures participating in the regulation of the convulsive-seizure threshold.