7-OH-DPAT,a dopamine D3-selective receptor agonist,produces contralateral rotation in 6-hydroxydopamine-lesioned rats

The purpose of the present study was to characterize the rotational behavior in unilateral 6-OHDA-lesioned rats produced by the high affinity and selective dopamine D₃ receptor ligand 7-OH-DPAT. Qualitatively similar to the direct-acting DA agonist apomorphine, 7-OH-DPAT causes rats to rotate in a direction contralateral to the side of the nigrostriatal DA pathway lesion. This effect is dose-dependent and the minimum effective dose is 0.03 mg (0.12 m?mol)/kg. 7-OH-DPAT-induced rotation is blocked in a dose-dependent manner by oral pretreatment with the “D₂-like” receptor antagonists haloperidol, eticlopride, or clozapine, but not by the “D₁-like” antagonist SCH 23390. The rank order potency for inhibition of 7-OH-DPAT rotation for haloperidol [ID₅₀ = 0.067 mg (0.18 m?mol)/kg], eticlopride [ID₅₀ = 0.41 mg (1.2 m?mol)/kg], clozapine [ID₅₀ = 13 mg (40 m?mol)/kg], and SCH 23390 [ID₅₀ > 90 mg (313 m?mol)/kg] closely parallels their rank order affinity for binding to either the D₂ or the D₃ receptor. Pretreatment with the non-DA receptor antagonists ritanserin (serotonin 5HT₂), scopolamine (muscarinic cholinergic), propranolol (betaadrenergic), or naltrexone (opiate), each at relevant pharmacological doses, failed to reduce 7-OH-DPAT rotation. Taken together, these results are consistent with mediation of 7-OH-DPAT-induced rotational behavior via an agonist interaction with one or more DA receptors. ©1995 Wiley-Liss, Inc.