Behavioural synergism between the dopamine agonists SKF 38393 and LY 171555 in dopamine-depleted mice: antagonism by sulpiride reveals only stimulant postsynaptic D-2 receptors.

The behavioural effects of the D-1 agonist SKF 38393 (0.56-45 mg/kg) and the D-2 agonist LY 171555 (0.05-6.25 mg/kg) were studied in mice rendered akinetic with a combination of reserpine and alpha-methyl-p-tyrosine (alpha-MPT). Under these conditions both agonists were behaviourally ineffective by themselves, but interacted synergistically to restore locomotor and orofacial movements. High levels of D-1 stimulation did not promote stereotypies at the expense of locomotion in dual reserpine- and alpha-MPT-treated mice, suggesting that the concomitant stimulation of D-1 receptors is essential both for the genesis and subsequent development of all components of D-2 behaviours. The motor stimulant effects of LY 171555 (0.05-1.25 mg/kg), administered in conjunction with a near-maximal dose of SKF 38393 (15 mg/kg), were dose-dependently inhibited by sulpiride at all doses tested (1, 10 and 50 mg/kg). The augmentation of D-2 behaviours by low doses of sulpiride, noted in an earlier study, was not observed here. Results with this particular combination of drugs therefore do not support the concept of mixed excitatory and inhibitory postsynaptic D-2 receptors. The results are discussed in terms of different D-2 agonists interacting with discrete subpopulations of D-2 receptors at postsynaptic sites.