Pharmacological and molecular mechanisms on amino acid receptor complexes in brain of animal model for drug abuse

The effects of intermittent intraperitoneal (i.p.) administration of cocaine (20mg /kg) ongabaィイd2aィエd2-benzodiazepine (bzd) receptors labeled by t[ィイd135ィエd1s] b u t ylbicyclophophorothionate(tbps),and on several types of mRNA subunits were investigated in rat brain by in vitro quantitativereceptor autoradiography and in situ hybridization. Phosphor screen imaging with high sensitivitya wide linear range of response was utilized for imaging analysis. There was a significantdecrease in the level of α1, α6, β2, β3，and γ2 subunits mRNA with no alteration of [D135 D1S] TBPS binding in any regions in the brain ofrats， at 1小时following a single injection of cocaine. In chronically treated-animals，the mean scores of stereotyped behavior increased with the number of injections. the level ofβ - 3 subunit mRNA was decreased in the cortices and caudate-putamenat 24小时after a final injection of chronic administrations for 14 days. In the withdrawal fromcocaine,the frontal cortex and hippocampal complexes showed a significant increase in [D135 D1S] TBPSbinding and α1 and β3 subunit mRNA in the rats 1周after a cessation of chronic administration ofcocaine. These findings suggest that the disruption of GABA D2A - bzd receptor formation isclosely involved in the development of cocaine-相关behavioral disturbances. Further studies onthe physiological functions on GABA D2A - bzd receptor complex will be necessary for anprecise mechanisms underlying the acute effectsdevelopment of hypersensitization, and withdrawal state of cocaine。

The effects of intermittent intraperitoneal (i.p.) administration of cocaine (20 mg/kg) on GABAィイD2AィエD2-benzodiazepine (BZD) receptors labeled by t-[ィイD135ィエD1S] butylbicyclophophorothionate (TBPS), and on several types of mRNA subunits were investigated in rat brain by in vitro quantitative receptor autoradiography and in situ hybridization. Phosphor screen imaging with high sensitivity and a wide linear range of response was utilized for imaging analysis. There was a significant decrease in the level of α1, α6, β2, β3, and γ2 subunits mRNA with no alteration of [ィイD135ィエD1S] TBPS binding in any regions in the brain of rats, at 1 hour following a single injection of cocaine. In chronically treated-animals, the mean scores of stereotyped behavior were increased with the number of injections. The level of β3 subunit mRNA was decreased in the cortices and caudate-putamen, at 24 hours after a final injection of chronic administrations for 14 days. In the withdrawal from cocaine, the frontal cortex and hippocampal complexes showed a significant increase in [ィイD135ィエD1S] TBPS binding and α1 and β3 subunit mRNA in the rats 1 week after a cessation of chronic administration of cocaine. These findings suggest that the disruption of GABAィイD2AィエD2-BZD receptor formation is closely involved in the development of cocaine-related behavioral disturbances. Further studies on the physiological functions on GABAィイD2AィエD2-BZD receptor complex will be necessary for an explanation of the precise mechanisms underlying the acute effects, development of hypersensitization, and withdrawal state of cocaine.