Time course of rat motility response to apomorphine: a simple model for studying preferential blockade of brain dopamine receptors mediating sedation

The present work proposes a simple behavioral method for studying the ability of certain neuroleptics to block preferentially dopamine receptors subserving sedation. The model is based on the temporally biphasic motor response induced in rats by a single critical dose of apomorphine. It was chosen from a preliminary apomorphine dose-response study which showed that the same doses between 6.25 and 625 micrograms/kg affected rat motility differently according to whether the animals were "naive" or "familiarized" to the apparatus for 90 min before administering the drug. When the motility response of naive rats to 300 micrograms/kg of apomorphine was recorded immediately after SC injection, an initial (1--5 min) inhibition and a subsequent (20--45 min) stimulation of motility were obtained. (--)-Sulpiride (1.25--50 mg/kg) was found to be approximately 6-fold more effective in counteracting the apomorphine inhibition than stimulation of locomotion. Haloperidol (0.005--0.1 mg/kg) incompletely antagonized apomorphine inhibition and markedly blocked stimulation, which suggests that it has no preferential activity on dopamine receptors subserving sedation. The results were in accordance with those obtained by other authors with different paradigms, and indicated that the time course of the rat motility response to a single dose of apomorphine may constitute a useful model for detecting selective influences on different dopamine receptors.