Behavioural effects of angiotensin II in the mouse following MPTP administration

1. The effects of the octapeptide angiotensin II (AT II) on some types of behaviour [threshold of seizures induced by timed intravenous infusion of pentylenetetrazol (PTZ), exploratory behaviour: ambulation, rearing and head-dips on a hole-board, and passive avoidance performance--step-through paradigm] were studied following repeated systemic administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) to mice (30 mg/kg, i.p., twice daily for 5 days). AT II was administered s.c. (200 micrograms/kg), single and repeated (for 7 days) 7 days after withdrawal of MPTP. 2. PTZ seizure threshold was significantly increased by AT II both in groups with single and repeated administration (stronger than in the group treated only with MPTP and in the group untreated with MPTP). 3. AT II significantly increased the ambulation and rearing as well as the head-dips both on single and repeated administration as compared to groups treated and untreated with MPTP. 4. Administered immediately after the passive training trial AT II, on single and repeated administration, significantly increased latencies, i.e. it facilitated retention, in MPTP-treated mice. 5. These results were discussed in the light of DA and perhaps, GABA receptor supersensitivity developed in susceptible brain structures after withdrawal of repeated MPTP administration. 6. The adaptive changes in the effects of AT II on seizure threshold, exploratory behaviour and retention of passive avoidance performance might be associated with the altered receptor-receptor (AT II-DA-GABA) interactions in the brain.