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;292:952-959], suggesting that conclusions about the interactions between the dopamine and cannabinoid receptor motor systems in rodents may not extend to primates.
Meschler
J P
JP
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 South Grand Boulevard, St. Louis, MO 63104, USA.
Conley
T J
TJ
Howlett
A C
AC
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology*; D003511:Cyclohexanols / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D007103:Immobilization / Q000502:physiology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D010617:Phenanthridines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology
D000700:Analgesics; D002186:Cannabinoids; D003511:Cyclohexanols; D018491:Dopamine Agonists; D010617:Phenanthridines; D011804:Quinolines; C074280:3-allyl-6-bromo-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; C025490:nantradol; C047726:quinelorane