Vol. 283, Issue 1, 7-15, 1997

Characterization of Unconditioned Behavioral Effects of Dopamine D₃/D₂ Receptor Agonists¹

Beth Geter-Douglass, Jonathan L. Katz, Ken Alling, Jane B. Acri and Jeffrey M. Witkin

Drug Development Group, Preclinical Pharmacology Laboratory, NIDA Addiction Research Center, National Institutes of Health, Baltimore, Maryland

A series of experiments examined the ability of dopamine D₃/D₂ receptor agonists [(+)-(4aR,10bR)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin-9-ol hydrochloride (PD 128,907), (±)-7-hydroxy-dipropylaminotetralin hydrobromide (7-OH-DPAT), quinpirole and bromocriptine] to produce a variety of dopaminergically mediated behaviors. The effects of these drugs with selectivity for D₃/D₂ receptors over D₁ receptors were compared with those produced by the selective D₁ agonists [(±)-Phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride (SKF 38393), (±)-6-Chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF 82958)], a nonselective dopaminergic agonist (apomorphine), and an indirect dopamine agonist (cocaine). The D₃/D₂ agonists decreased locomotor activity, had no effect on gnawing and only inconsistently induced climbing in mice. Further, these agonists dose-dependently produced scratching in squirrel monkeys. In contrast, the D₁ agonists, SKF 82958 and SKF 38393, did not produce scratching in squirrel monkeys. Whereas the full D₁ agonist, SKF 82958, produced increases in locomotor activity and in climbing and gnawing, the partial D₁ agonist, SKF 38393, did not increase the frequencies of these behaviors. The nonselective dopamine agonist, apomorphine, produced decreases in locomotor activity and increases in climbing and gnawing in mice. Apomorphine dose-dependently produced scratching in squirrel monkeys. The indirect dopamine agonist, cocaine, produced increases in locomotor activity and climbing, but had no effect on climbing or gnawing in mice and did not produce scratching in squirrel monkeys. These findings suggest that D₃/D₂ agonists can be distinguished on various behavioral measures from the nonselective agonist, apomorphine (gnawing), D₁ agonists (scratching) and the indirect agonist, cocaine (locomotor activity and scratching). Behaviors once attributed to stimulation of D₂ (locomotor activity and scratching) or D₁/D₂ (climbing and gnawing) receptors may also involve dopamine D₃ receptors.