Dopamine receptors in rat striatum and nucleus accumbens; conformational studies using rigid analogues of dopamine

Author:

Woodruff G N1,Watling K J1,Andrews C D1,Poat Judith A1,McDermed J D2

Affiliation:

1. Department of Physiology & Biochemistry, University of Southampton, Southampton SO9 3TU, UK

2. Wellcome Research Laboratories, North Carolina 27709, USA

Abstract

Abstract A study was made of the actions of dopamine and of some 2-amino-1,2,3,4-tetrahydronaphthalenes on dopamine-sensitive adenylate cyclase in homogenates of rat striatum and nucleus accumbens. The compounds were also tested for their ability to stimulate motor activity following bilateral injection into the nucleus accumbens of conscious rats. The most active compounds on adenylate cyclase from both striatum and nucleus accumbens were dopamine and 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene(6,7-diOHATN). The 5,6-dihydroxy analogue (5,6-diOHATN) was 50 times less active than 6,7-diOHATN in striatal homogenates and 350 times less active in homogenates of nucleus accumbens. All dihydroxy compounds tested were active in causing stimulation of motor activity, the most active compounds being 6,7- and 5,6-diOHATN. Both dimethoxy derivatives tested were inactive on the adenylate cyclase and as locomotor stimulants.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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