Our purpose was to gain insight into a possible modulatory role for μ, δ, and κ opioid receptors by neuroleptics (chlorpromazine, thioridazine, haloperidol, sulpiride, and pimozide) in chronic morphine 5 mg/kg and 20 mg/kg treated mouse striatum. We attempted quantitative receptor assays using highly specific radioligands, [³H] DAGO ([D-Ala², N-Mephe⁴, Glycol⁵] enkephalin), [³H]DPDPE ([D-Pen², D-Pen⁵] enkephalin) and [³H] DPN(diprenorphine) to measure the binding affinity in the experimental groups. The decrease of [³H]DAGO binding was potentiated by sulpiride and pimozide in the chronic morphine treatment (5 mg/kg and 20 mg/kg). The decrease of [³H]DPDPE binding was inhibited by chlorpromazine, thioridazine, haloperidol, sulpiride, and pimozide in chronic morphine treatment (5 mg/kg and 20 mg/kg). The decrease of [³H] DPN binding was significantly inhibited by chlorpromazine, thioridazine, sulpiride, and pimozide in chronic morphine 20 mg/kg treatment. [³H] DPN binding on the neuroleptics was antagonized by naloxone pretreatment in chronic morphine 20 mg/kg treatment. These findings suggest that neuroleptics influence opposing tonically active on the δ, and κ opioid receptor compared with μ opioid receptor in the chronic morphine treated mouse striatum.