Behavioural effects of 7-OH-DPAT are solely due to stimulation of dopamine D2 receptors in the shell of the nucleus accumbens; turning behaviour.
The goal of this study was to determine whether the dopamine D3 receptor in limbic structures plays a role in the shell-specific and dopamine-dependent display of turning behaviour in rats. When combined with the dopamine D1 receptor agonist (+/-)-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine-7,8-diol (SKF-38393, 5 micrograms), the putative dopamine D3 receptor agonist (+/-)-7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT, 1, 5 and 10 micrograms) elicited contralateral turning in a dose-dependent manner following unilateral injection into the shell, but not the core, of the nucleus accumbens. The turning pattern displayed was identical to that reported previously after intra-accumbens administration of the cocktail of SKF-38393 and the dopamine D2 receptor agonist quinpirole. The behaviour under study was dose-dependently attenuated by local administration of the dopamine D1 receptor antagonist R(+)-7-chloro-8-hydroxy-3- methyl-I-phroyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH 23390: 10 and 100 ng), the dopamine D2 receptor antagonist domperidone (25 and 50 ng) or the dopamine D2/3 receptor antagonist l-sulpiride (5 and 25 ng). Combined blockade of both dopamine D1 and D2 receptors in the shell with a dose of either antagonist alone that produced just a moderate reduction (10 ng SCH 23390 and 50 ng domperidone) completely antagonized the turning behaviour elicited by the cocktail of SKF-38393 and 7-OH-DPAT. Replacing 7-OH-DPAT by another putative dopamine D3 receptor agonist,S(+)-(4aR, 10bR)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4, 3-b]-1, 4-oxazin-9-ol (PD 128,907, 10 micrograms), in the cocktail did produce no turning behaviour at all. It is concluded that mesolimbic dopamine D3 receptors play no role in the dopamine-dependent and shell-specific turning behaviour: the contribution of 7-OH-DPAT in the cocktail of SKF-38393 and 7-OH-DPAT to the display of turning behaviour is solely due to its ability to activate dopamine D2 receptors.
Koshikawa
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Department of Pharmacology, Nihon University School of Dentistry, Tokyo, Japan.
Kitamura
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M
Kobayashi
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M
Cools
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AR
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D004294:Domperidone / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D008297:Male; D009068:Movement / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D010078:Oxazines / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D013469:Sulpiride / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D001552:Benzazepines; D001578:Benzopyrans; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D010078:Oxazines; D017448:Receptors, Dopamine D2; D013764:Tetrahydronaphthalenes; C062458:3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol; D019257:Quinpirole; D004294:Domperidone; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride; C031349:7-hydroxy-2-N,N-dipropylaminotetralin