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

마우스 선조체에서 Opioid 수용체 결합에 대한 Neuroleptics의 영향

  • Kim, Soo-Kyung (Department of Pharmacology and Institute for Medical Science, Keimyung University School of Medicine) ;
  • Lee, Seong-Ryong (Department of Pharmacology and Institute for Medical Science, Keimyung University School of Medicine) ;
  • Park, Chang-Gyo (Department of Pharmacology and Institute for Medical Science, Keimyung University School of Medicine)
  • 김수경 (계명대학교 의과대학 약리학교실) ;
  • 이성룡 (계명대학교 의과대학 약리학교실) ;
  • 박창교 (계명대학교 의과대학 약리학교실)
  • Published : 1994.12.30

Abstract

Our purpose was to gain insight into a possible modulatory role for ${\mu},\;{\delta},\;and\;{\kappa}$ 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, $[^3H]\;DAGO\;([D-Ala^2,\;N-Mephe^4,\;Glycol^5]\;enkephalin)$, $[^3H]DPDPE\;([D-Pen^2,\;D-Pen^5]\;enkephalin)$ 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 ${\delta},\;and\;{\kappa}$ opioid receptor compared with ${\mu}$ opioid receptor in the chronic morphine treated mouse striatum.

이 연구에서는 선조체에서 opioid 신경계와 dopamine 신경계의 상호 관계를 알아보기 위해서 morphine을 5m/kg, 20 mg/kg로 10일간 복강내 투여한 후 chlorpromazine, thioridazine, haloperidol, sulpiride, pimozide를 투여하였다. Opioid ${\mu},\;{\delta},\;{\kappa}$ 수용체의 binding의 변화를 관찰하고자 $[^3H]\;DAGO$, $[^3H]\;DPDPE$, 및 $[^3H]\;DPN$ binding assay를 하였으며, 그 결과 morphine (20 mg/kg) 장기 투여된 실험군에서 $[^3H]\;DAGO$, $[^3H]\;DPDPE$, 및 $[^3H]\;DPN$ 결합이 감소되었다. Morphine 20 mg/kg 장기 투여군에 chlorpromazine, thioridazine 주사시에는 morphine 5mg/kg 투여군에 비하여 $[^3H]\;DAGO$ 결합의 감소와, $[^3H]\;DPDPE$, 및 $[^3H]\;DPN$ 결합의 증가를 나타내었고, haloperidol 주사군은 $[^3H]\;DAGO$, $[^3H]\;DPN$ 결합의 감소, 및 $[^3H]\;DPDPE$ 결합의 증가를 나타내었다. Sulpiride, pimozide 주사군은 morphine 5 m/kg 투여군에 비하여 20m/kg 투여군에서 $[^3H]\;DAGO$, $[^3H]\;DPDPE$, 및 $[^3H]\;DPN$ 결합의 증가를 나타내었다. 이상의 결과로 보아 각 약물간의 opioid 결합에 대한 차이점은 있었으나, morphine 5mg/kg 투여군보다 20m/kg 투여군에서 $[^3H]\;DPDPE$$[^3H]\;DPN$의 결합이 증가의 경향을 보임으로써, 다량의 morphine을 투여했을 때 ${\mu}\;opioid$ 수용체에 비하여 ${\delta}${\kappa}\;opioid$ 수용체가 더 활성화되는 것을 알 수 있었다.

Keywords