Characterization of unconditioned behavioral effects of dopamine D3/D2 receptor agonists.
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]b enzopyrano-[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-be nzazepine 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.
Geter-Douglass
B
B
Preclinical Pharmacology Laboratory, NIDA Addiction Research Center, National Institutes of Health, Baltimore, Maryland 21224, USA.
Katz
J L
JL
Alling
K
K
Acri
J B
JB
Witkin
J M
JM
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3
D018491:Dopamine Agonists; C493594:Drd3 protein, mouse; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D003042:Cocaine; D001058:Apomorphine