EFFECTS OF B-HT-920 ON NIGROSTRIATAL AND MESOLIMBIC DOPAMINE SYSTEMS IN NORMOSENSITIVE AND SUPERSENSITIVE RATS

被引:13
作者
CLARKE, PBS [1 ]
WYDER, KJ [1 ]
JAKUBOVIC, A [1 ]
FIBIGER, HC [1 ]
机构
[1] UNIV BRITISH COLUMBIA, DEPT PSYCHIAT, DIV NEUROL SCI, VANCOUVER V6T 2A1, BC, CANADA
关键词
D O I
10.1111/j.1476-5381.1990.tb12959.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
B-HT 920, a D2 dopamine receptor agonist, was tested for its ability to exert presynaptic actions in normosensitive rats, and for possible postsynaptic actions in rats made 'supersensitive' to apomorphine. In normosensitive rats, B-HT 920 (0.01-0.3 mg kg-1, i.p.) increased dopamine concentrations and lowered metabolite levels to a similar extent in all four terminal regions examined (medial prefrontal cortex, olfactory tubercle, nucleus accumbens, caudate-putamen). Analogous effects were seen for 5-hydroxytryptamine and its metabolite 5-hydroxyindoleacetic acid. Rats which received bilateral 6-hydroxydopamine (6-OHDA) infusions into the caudate-putamen showed signs of postsynaptic dopamine receptor activation (stereotyped behaviour) in response to B-HT 920 (0.1 and 1.0 mg kg-1, i.p.) and to apomorphine (0.2 mg kg-1, s.c.). Similarly, B-HT 920 (0.1 mg kg-1) induced contralateral circling in rats that had received unilateral 6-OHDA infusions into the medial forebrain bundle; the rate of circling increased gradually over several weeks. In contrast, bilateral 6-OHDA infusions into the nucleus accumbens resulted in a supersensitive (locomotor stimulant) response to a low dose of apomorphine (0.1 mg kg-1, s.c.), but not to B-HT 920 (0.01 and 0.1 mg kg-1). In intact rats, withdrawal of chronic haloperidol treatment induced behavioural supersensitivity to apomorphine but not to B-HT 920.
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页码:509 / 515
页数:7
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