CHARACTERIZATION OF UNCONDITIONED BEHAVIORAL-EFFECTS OF DOPAMINE D-3 D-2 RECEPTOR AGONISTS/

A series of experiments examined the ability of dopamine D-3/D-2 recep tor agonists +)-(4aR,10bR)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H -[1]be nzopyrano-[4,3-b]-1, oxazin-9-ol hydrochloride (PD 128,907), (+/-)-7-h ydroxy-dipropylaminotetralin hydrobromide (7-OH-DPAT), quinpirole and bromocriptine] to produce a variety of dopaminergically mediated behav iors. The effects of these drugs with selectivity for D-3/D-2 receptor s over D-1 receptors were compared with those produced by the selectiv e D-1 agonists [(+/-)-Phenyl-2,3,4,5-tetrahydro-(1 H)-3-benzazepine-7, 8-diol hydrochloride (SKF 38393), -7,8-dihydroxy-3-allyl-1-phenyl-2,3, 4,5-tetrahydro -1H-3-benzazepine hydrobromide (SKF 82958)], a nonselec tive dopaminergic agonist (apomorphine), and an indirect dopamine agon ist (cocaine). The D-3/D-2 agonists decreased locomotor activity, had no effect on gnawing and only inconsistently induced climbing in mice. Further, these agonists dose-dependently produced scratching in squir rel monkeys. In contrast, the D-1 agonists, SKF 82958 and SKF 38393, d id not produce scratching in squirrel monkeys, Whereas the full D-1 ag onist, SKF 82958, produced increases in locomotor activity and in clim bing and gnawing, the partial D-1 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, cocain e, produced increases in locomotor activity and climbing, but had no e ffect on climbing or gnawing in mice and did not produce scratching in squirrel monkeys. These findings suggest that D-3/D-2 agonists can be distinguished on various behavioral measures from the nonselective ag onist, apomorphine (gnawing), D-1 agonists (scratching) and the indire ct agonist, cocaine (locomotor activity and scratching). Behaviors onc e attributed to stimulation of D-2 (locomotor activity and scratching) or D-1/D-2 (climbing and gnawing) receptors may also involve dopamine D-3 receptors.