Cannabinoid and dopamine interaction in rodent brain: effects on locomotor activity

We investigated interactions between cannabinoid and dopamine receptor systems in ICR mice. Mice were treated with the cannabinoid agonist levonantradol, the D-1 dopamine agonist 6-Br-APB, or the D-2 dopamine agonist quinelorane, or with combinations of these drugs. In addition, the D-1 antagonist SCH23390 was administered both alone and in combination with levonantradol. Two tests were used to evaluate changes in motor function: the immobility (ring stand) test and the catalepsy (bar) test. Levonantradol increased immobility and catalepsy in a dose-dependant manner. Both the D-2 agonist quinelorane and the D-1 agonist 6-Br-APB were able to attenuate the motor dysfunction caused by levonantradol. Administration of the D-1 antagonist SCH23390 enhanced the effects of levonantradol, producing a leftward shift of the log dose-response curve. These results differ from the augmentation by D-2 agonists of the hypoactivity induced by levonantradol in non-human primates [Meschler JP, Clarkson FA, Mathew PJ, Howlett AC, Madras BK. D-2, but not D-1 dopamine receptor agonists potentiate cannabinoid-induced sedation in nonhuman primates. J Pharmacol Exp Ther 2000;292:952-9], suggesting that conclusions about the interactions between the dopamine and cannabinoid receptor motor systems in rodents may not extend to primates. (C) 2000 Elsevier Science Inc. All rights reserved.