Effects of acute administration of DA agonists on locomotor activity: MPTP versus neonatal intracerebroventricular 6-OHDA treatment

The effects of several dopamine (DA) receptor agonists upon locomotor activity on adult MPTP-treated mice and postnatal 6-hydroxydopamine- (6-OHDA-) treated rats were assessed in ten experiments. C57 BL/6 mice were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 2 x 40 mg/kg, s.c., 24-hr interval between injections) at 5-months-age, while 1-day-old male Wistar rat pups were given intracisternal 6-OHDA (50 mg, once following desipramine, 25 mg/kg). MPTP-treated mice were tested 4-5 weeks following MPTP injections whereas neonatal 6-OHDA rats were tested at 3-months-age. Locomotor activity was measured in respective activity test chambers following acute administration of DA receptor agonists. In MPTP-treated mice, apomorphine failed to elevate locomotor activity but instead further exacerbated (1.0 and 3.0 mg/kg, s.c.) the hypokinesia of these animals while inducing marked increases in control mice. Cabergoline (0.3 mg/kg, s.c.) and bromocriptine (3.0 mg/kg, s.c.) caused dose-specific elevations of locomotion in MPTP and control mice but suppressed activity at the highest doses. Quinpirole (0.2 mg/kg) and 7-hydroxydipropylaminotetralin (7-OH-DPAT; 300 nmole/kg) increased locomotion in hypokinesic MPTP-treated mice; in control mice, activity was elevated by quinpirole (0.2 and 0.7 mg/kg) and 7-OH-DPAT (100 and 300 nmole/kg), while higher doses suppressed activity. Neither SKF 38393 (1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol) nor FCE 23884 4-(9,10-didehydro-6-methylergolin-8 beta-yl) methyl-piperazine-2,6-dione] affected locomotor activity. Apomorphine (0.3, 1.0 and 2.0 mg/kg), bromocriptine (3.0 mg/kg) and cabergoline (1.0 mg/kg) stimulated locomotion in sham-operated rats, and to a greater extent in the 6-OHDA-treated rats. Higher dose cabergoline (3.0 mg/kg) induced increased activity of similar extent in sham controls and 6-OHDA treated rats. Activity-enhancing effects of quinpirole (0.2, 0.7 and 2.1 mg/kg) in sham rats were attenuated in 6-OHDA treated rats. Both SKF 38393 (10 mg/kg) and FCE 23884 (0.3 and 1.0 mg/kg) induced locomotor activity increases in 6-OHDA, but not sham, rats. Finally, 7-OH-DPAT (1200 mg/kg) enhanced activity in 6-OHDA rats vs. shams. The effects of the DA agonists are discussed with regard to the putative antihypokinesic effects in MPTP mice and DA-receptor supersensitivity effects in neonatal 6-OHDA rats, pertaining to their more-or-less selective subreceptor profiles.