ACTIONS OF (+ -)-7-HYDROXY-N,N-DIPROPYLAMINOTETRALIN (7-OH-DPAT) ON DOPAMINE SYNTHESIS IN LIMBIC AND EXTRAPYRAMIDAL REGIONS OF RAT-BRAIN/

The proposed D-3-selective ligand (+/-)-7-hydroxy-N,N-dipropylaminotet ralin (7-OH-DPAT) inhibited tyrosine hydroxylase in vitro (IC50 = 0.6- 0.7 mu M) and dihydroxyphenylalanine (DOPA) accumulation in vivo (ID50 = 4.8-6.4 mg/kg) in two autoreceptor models in extrapyramidal and lim bic tissue in rat forebrain, without consistent regional selectivity. Some limbic selectivity (ID50 = 10 vs. 29 mg/kg) was found in an in vi vo model permitting expression of postsynaptic D-3 and D-2 receptor ac tivity. The effects were partially blocked by S(-)-eticlopride alone, and fury after reserpine pretreatment. The results suggest that 7-OH-D PAT activates D-3 or D-2 autoreceptors, alters dopamine storage or rel ease, and may interact with some limbic selectivity at postsynaptic D- 3 and D-2 receptors as a partial agonist.