Effects of Neuroleptics on the Opioid Receptor Binding in the Mouse Striatum

Abstract

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.

이 연구에서는 선조체에서 opioid 신경계와 dopamine 신경계의 상호 관계를 알아보기 위해서 morphine을 5mg/kg 20 mg/kg로 10일간 복강내 투여한 후 chlorpromazine，thioridazine, haloperidol, sulpiride, pimozide를 투여하였다. Opioid μ, δ, κ 수용체의 binding의 변화를 관찰 하고자 [3H] DAGO, [3H] DPDPE, 및 [3H] DPN binding assay를 하였으며, 그 결과 morphine (20 mg/kg) 장기 투여된 실험군에서 [3H] DAGO, [3H] DPDPE, 및 [3H] DPN 결합이 감소되었 다. Morphine 20 mg/kg 장기 투여군에 chlorpromazine, thioridazine 주사시에는 morphine 5mg/kg 투여군에 비하여 [3H] DAGO 결합의 감소와, [3H] DPDPE, 및 [3H] DPN 결합의 증가 를 나타내었고, haloperidol 주사군은 [3H] DAGO, [3H] DPN 결합의 감소，및 [3H] DPDPE 결 합희 증가를 나타내었다. Sulpiride, pimozide 주사군은 morphine 5 mg/kg 투여군에 비하여 20 mg/kg 투여군에서 [3H]DAGO, [[3H] DPDPE, 및 [3H] DPN 결합의 증가틀 나타내었다.

이상의 결과로 보아 각 약물간의 opioid 결합에 대한 차이점은 있었으나, morphine 5mg/kg 투 여군보다 20 mg/kg 투여군에서 [3H] DPDPE 및 [3H] DPN의 결합이 증가의 경향을 보임으로써， 다량의 morphine을 투여했을 때 μ opioid 수용체에 비하여 δ와 κ opioid 수용체가 더 활성화되는 것을 알 수 있었다.