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-dipropylaminotetralin (7-OH-DPAT) inhibited tyrosine hydroxylase in vitro (IC 50 = 0.6–0.7 μM) and dihydroxyphenylalanine (DOPA) accimulation in vivo (ID 50 = 4.8–6.4 mg/kg) in two autoreceptor models in extrapyramidal and limbic tissue in rat forebrain, without consistent regional selectivity. Some limbic selectivity (ID 50 = 10 vs. 29 mg/kg) was found in an in vivo model permitting expression of postsynaptic D 3 and D 2 receptor activity. The effects were partially blocked by S(−)-eticlopride alone, and fully after reserpine pretreatment. The results suggest that 7-OH-DPAT activates D 3 or D 2 autoreceptors, alters dopamine storage or release, and may interact with some limbic selectivity at postsynaptic D 3 and D 2 receptors as a partial agonist.