항정신병약 투여에 따른 GABA 수용체의 변화

GABA-Receptor Changes Induced by An Antipsychotic Agent, Haloperidol

This study was designed to investigate the GABA A and B receptor changes, followed by the administration of an antipsychotic agent, haloperidol in the rat cerebral cortex and cerebellum using 3H-GABA ligand binding method. The Sprague-Dawley rats weighting 160&#12316; 180 gm were divided into 2 groups ; one day dose group and 28 day-administration group. Each group was subdivided into 2.5 mg/kg of haloperidol-administered group and 5.0 mg/kg of haloperidoladministered group. Also, We examined the effect of haloperidol on the postsynaptic dopamine receptor of the rat corpus striatum by 3H-spiperidol binding method. The results were as follows : 1) Mean values of Bm ax and K d for 3H-GABA in GABA A rceptor of cerebral cortex in one-day dose group, were 16.41 士 7.21 fmoles/mg protein, 2.20± 1.09 nM for 2.5 mg/kg of haloperidol- administered group, and 23.76士 7.37 fmoles/mg protein, 3.60± 0.09 nM for 5.0 mg/kg of haloperidol-administered group, respectively. Controls had 10.77土 3.86 fmoles/mg protein of Bm ax and 1.59± 0.56 nM of K d, respectively. A significant difference was seen between 5.0 mg/kg of haloperidol-administered group and control(尸<0.01). In cerebellum, both 2.5 mg/kg of haloperidol-administered group(7.82土 0.11 fmoles/mg protein, 1.42± 0.19 nM) and 5.0 mg/kg of haloperidol-administered group(8.24士 0.21 fmoles/mg protein, 1.58士 0.01 nM) were significantly different from controls(6.10± 0.71 fmoles/mg protein, 1.07± 0.02 nM, P<0 .01). 2) Mean values of Bmax and Kd for 3H-GABA in GABA A receptor of cerebral cortex in 28 day-administration group were 12.31士 5.12 fmoles/mg protein, 2.19士 0.85 nM for 2.5 mg/kg of haloperidol-administered group, and 14.80士 4.01 fmoles/mg protein, 2.73± 1.15 nM for 5.0 mg/kg of haloperidol-administered group, respectively. Controls had 14.79土 6.39 fmoles/ mg protein of Bmax and 1.39± 0.29 nM of K d, respectively. There were no significant differences between each group and controls. In cerebellum, 5.0 mg/kg of haloperidol-administered group(BwflA： : 11.49±0.61 fmoles/mg protein, &#8226; 1.23± 0.36 nM) was significantly different from those of control(Bmar * 8.60±0.84 fmoles/mg protein, K d : 0.88± 0.17 nM). There was no significant difference between 2.5mg/kg of haloperidol-administered group(8.58± 0.45 fmoles/mg protein, 0.84士 0.25 nM) and controls. 3) Mean values of Bm ax and Y d for 3H-GABA in GABA B receptor of cerebral cortex in one-day dose group were 20.66士 8.38 fmoles/mg protein, 2.94土 1.24 nM for 2.5 mg/kg of haloperidol-administered group, and 29.29土 11.65 fmoles/mg protein, 4.62± 0.92 nM for 5.0 mg/kg of haloperidol-administered group, respectively. Controls had 12.82± 5.58 fmoles/mg protein of V>max and 1.97±0.43 nM of Kd. There were significant differences between both groups and controls(P<0.0l). In cerebellum, both of 2.5 mg/kg of haloperidol-administered group(10.90土 0.25 fmoles/mg protein, 2.25士 0.24 nM) and 5.0 mg/kg of haloperidol-administered group(10.46± 0.65 fmoles/mg protein, 2.25± 0.24 nM) were significantly different from controls(8.06土 1.61 fmoles/mg protein, 1.67± 0.24 nM, P<0.01) in B m ax and Kd. 4) Mean values of Bm ax and K J for 3H-GABA in GABA B receptor of cerebral cortex in 28-day-administration group were 13.04± 4.28 fmoles/mg protein, 2.39士 0.60 nM for 2.5 mg/kg of haloperidol-administered group and 16.52± 4.18 fmoles/mg protein, 3.14士 1.22 nM for 5.0 mg/kg of haloperidol-administered group, respectively. Controls had 16.10土 4.28 fmoles/ mg protein of Bm ax and 1.40±0.17 nM of K^. There was a significant difference between K d of 5.0 mg/kg of haloperidol-administered group and controls(^<0.05). In cerebellum, both of 2.5 mg/kg of haloperidol-administered group(11.23土 0.65 fmoles/mg protein, 1.42± 0.38 nM) and 5.0 mg