In forced-swim tests in mice and rats, the novel D 3 /D 2 receptor agonist S32504 [(ϩ)-trans-3,4,4a,5,6,10b-hexahydro-9-carbamoyl-4-propyl-2H-naphth[1,2-b]-1,4-oxazine] dose-dependently (0.04 -2.5 mg/kg) and stereospecifically suppressed immobility compared with its enantiomer S32601 [(Ϫ)-trans-3,4,4a,5,6,10b-hexahydro-9-carbamoyl-4-propyl-2H-naphth-[1,2-b]-1,4-oxazine]. Ropinirole was less potent than S32504 in this procedure, and it was likewise less potent than S32504 (0.04 -2.5 mg/kg) in attenuating motor-suppressant properties of the ␣ 2 -adrenoceptor agonist S18616 [(S)-spiro[(1-oxa-2-amino-3-azacyclopent-2-ene)-4,2Ј-(1Ј,2Ј,3Ј,4Ј-tetrahydronaphthalene)]]. In a learned helplessness paradigm, S32504 (0.08 -2.5 mg/kg) suppressed escape failures. Furthermore, in a chronic mild stress model of anhedonia, S32504 (0.16 -2.5 mg/kg) rapidly restored the suppression of sucrose consumption. S32504 inhibited marble-burying behavior in mice (0.04 -0.16 mg/kg) and aggressive behavior in isolated mice (0.04 -2.5 mg/kg): only higher doses of ropinirole mimicked these actions of S32504. In tests of anxiolytic activity, S32504 was more potent (0.0025-0.16 mg/kg) than ropinirole in suppressing fear-induced ultrasonic vocalizations, and S32601 was inactive. Furthermore, in contrast to ropinirole, S32504 modestly enhanced punished responses in a Vogel conflict procedure and increased open-arm entries in a plus-maze. At doses active in the above-described procedures, S32504 did not elicit hyperlocomotion. In the forced-swim, marble-burying, and ultrasonic vocalization models, actions of S32504 were Although the most familiar feature of Parkinson's disease is a disruption of motor function, it is accompanied by mood, sensory, and cognitive symptoms (Giladi et al., 2000). These often anticipate onset of frank motor dysfunction and are, in general, poorly treated by the prototypical antiparkinsonian agent L-3,4-dihydroxyphenylalanine (Giladi et al., 2000;Rascol et al., 2003). A perturbation of adrenergic, serotonergic, and cholinergic transmission likely contributes to these interrelated features of Parkinson's disease, but the principal underlying deficit is a degeneration of nigrostriatal dopaminergic projections together with a (less pronounced) dysfunction of mesolimbic and mesocortical dopaminergic pathways (Rascol et al., 2003). Interestingly, as indicated by the following observations, a disruption of dopaminergic transmission is implicated in the depressed mood displayed both by ParArticle, publication date, and citation information can be found at
