Differential effects of clonidine, B-HT 933 and B-HT 920 in immature rat pups

The effects of the alpha-adrenergic agonist clonidine were compared with two experimental hypotensive drugs, B-HT 920 and B-HT 933, in 10-day-old rat pups. Clonidine induced the expected dose-dependent (0.1-1.0 mg/kg) motor activation and wall-climbing syndrome typical at this age. B-HT 933, thought to be a more selective alpha 2-agonist than clonidine, elicited locomotor activity and wall-climbing only at the highest dose used (50 mg/kg). The high dose of B-HT 933 necessary to begin to mimic the effects of clonidine, a finding consistent with some studies using B-HT 933 in adults, suggests that the wall-climbing syndrome is mediated by receptors which have a low affinity for B-HT 933. In striking contrast, B-HT 920, a presynaptic dopamine agonist in mature rats, produced a very different behavioral profile. B-HT 920 induced long periods of sniffing accompanied by locomotion at low doses (peak at 0.12 mg/kg) and ataxic locomotion and poorly coordinated wall-climbing at high doses (30-50 mg/kg). Experiment 2 demonstrated that the active sniffing evoked by low doses of B-HT 920 was dose-dependently blocked by haloperidol (0.035-1.0 mg/kg). These findings of behavioral effects in 10-day-old rats suggest that B-HT 920 stimulates dopaminergic receptors in immature rats, presumably located on postsynaptic neurons. We propose that B-HT 920 and B-HT 933 also may be differentiated in terms of the time of onset of functional development of dopaminergic and noradrenergic autoreceptors, respectively.