Cannabis is a widely used illicit drug and state referenda are sanctioning its use as a medicine Dopamine agonists are effective therapeutic agents for Parkinson's disease, endocrine diseases and are candidate medications for cocaine addiction Increasing evidence in rodents suggests that cannabinoids antagonize dopamine responses at the behavioral and cellular level Medicinal and illicit use of each drug class raises the potential for concomitant use and supports the need to investigate whether antagonism of cannabinoid effects by dopamine agonists, observed in rodents, extends to primates We investigated the effects of a CB1 cannabinoid agonist, dopamine receptor agonists and their interaction on unconditioned behaviors in cynomolgus monkeys Administration of the CB1 agonist levonantradol alone (0 01 - 0 3 mg/kg) significantly decreased locomotor, general activity and sedation, but did not induce rigidity When administered alone, the D2 agonist quineloran e (0 03 - 1 0 mg/kg) produced hyperactivity in two monkeys, whereas the D2 agonist pergolide and the D1 agonists SKF 81297 failed to produce marked changes in activity Administration of an ineffective dose of levonantradol (0 03 mg/kg, determined from a dose-response curve) followed by a D2 receptor agonist precipitated sedation and a decrease in general and locomotor activity In contrast, when an ineffective dose of levonantradol was administered prior to the D1 agonist SKF 81297, no significant changes in motor activity or sedation occurred D2 potentiation of CB1 agonist-induced sedation suggests a unique interaction between these two receptor systems in primate brain Four significant conclusions can be drawn from these results 1 The unconditioned behavioral effects of CB1 agonists in primates differ from those reported in rodents 2 The paradoxical D2-induced potentiation of a cannabinoid agonist differs markedly from what would be predicted based on the behavioral effects of the drugs given alone 3 Preliminiary data suggest that potentiation of cannabinoid-induced sedation appears to be restricted to D2 and not D1 agonists 4 These data have clinical implications, particularly if they generalize to marijuana PUBLICATION Meschler JP, Clarkson FA, Mathews PJ, Howlett AC, Madras BK Cannabinoid and dopamine agonists interact to produce paradoxical behavioral effects in non-human primates Naunyn-Schmiedeberg's Arch Pharmacol 358 R58, 1998
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