COCAINE AND D-AMPHETAMINE INDUCE CHANGES IN CENTRAL BETA-ADRENOCEPTOR SENSITIVITY - EFFECTS OF ACUTE AND CHRONIC DRUG-TREATMENT

被引:58
作者
BANERJEE, SP
SHARMA, VK
KUNGCHEUNG, LS
CHANDA, SK
RIGGI, SJ
机构
[1] UNIV ROCHESTER, MED CTR, SCH MED & DENT, DEPT PHARMACOL & TOXICOL, ROCHESTER, NY 14642 USA
[2] PENNWALT CORP, DEPT PHARMACOL, DIV PHARMACEUT, ROCHESTER, NY 14623 USA
关键词
D O I
10.1016/0006-8993(79)90518-3
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The effects of acute and chronic treatment with psychomotor stimulants on specific binding of [3H]dihydroalprenolol to .beta.-adrenoceptors in rat brain were examined. At a dose of 10 mg/kg both acute and chronic treatment with cocaine and chronic treatment with D-amphetamine (10 mg/kg) caused increased binding of [3H]dihydroalprenolol. The molecular mechanism for this enhanced binding appears to be augmentation of the density of .beta.-adrenoceptors in rat brain. At a lower dose (5 mg/kg) chronic administration of D-amphetamine caused a decrease in the density of .beta.-adrenoceptors in rat brain. Chronic treatment with either D-amphetamine (10 mg/kg) or cocaine induced a marked increase in the magnitude of cyclic AMP accumulation in rat brain slices elicited by norepinephrine. Acute as well as chronic administration of D-amphetamine in vivo inhibited the temperature-dependent uptake of [3H]norepinephrine in rat brain synaptosomal homogenates, but no such inhibition was observed after chronic or acute treatment with cocaine. Psychomotor stimulants evidently induce .beta.-adrenoceptor supersensitivity which may be involved in the phenomenon of reverse tolerance and possibly psychosis in humans. The development of .beta.-adrenoceptor supersensitivity does not appear to be mediated through alterations in norepinephrine transport at the presynaptic sites.
引用
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页码:119 / 130
页数:12
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