Behavioural effects of 7-OH-DPAT are solely due to stimulation of dopamine D2 receptors in the shell of the nucleus accumbens; turning behaviour

Abstract

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 receptor agonist (± )-i-phenyl-2,3,4,5-tetrahydro-1 //-3-benzazepine-7,8-diol (SKF-38393, 5 jx g ) , the putative dopamine D3 receptor agonist (±)-7-hydroxy-/V,N-di-n-propyl-2-aminotetralin (7-OH-DPAT, 1, 5 and 10 jJLg) 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 Dj receptor antagonist /?(-h)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1//-3-benzazepi ne (SCH 23390: 10 and 100 ng), the dopamine D2 receptor antagonist domperidone (25 and 50 ng) or the dopamine D2/3 receptor antagonist /-sulpiride (5 and 25 ng). Combined blockade of both dopamine Dj 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, 5( + )-(4a/?,10W?)-3,4,4tf,10£~tetrahydro-4-propyl-2tf,5//-[l]benzopyrano [4,[3][4][5][6]907, 10 jxg), 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,

S32504, a Novel Naphtoxazine Agonist at Dopamine D3/D2 Receptors: II. Actions in Rodent, Primate, and Cellular Models of Antiparkinsonian Activity in Comparison to Ropinirole

“…Accordingly, S32504 dose-dependently, stereospecifically, and potently elicited contralateral rotation, an action mimicked (less potently) by ropinirole and L-DOPA (Eden et al, 1991). Although structures other than the striatum are implicated in the motor drive underlying rotation, it principally reflects a supersensitivity (enhanced density) of striatal D 2 receptors (Koshikawa et al, 1996;Araki et al, 2000;Newman-Tancredi et al, 2001). Correspondingly, extending studies with a further D 2 /D 3 agonist, quinerolane (Newman-Tancredi et al, 2001), S32504-induced rotation was blocked by the preferential D 2 receptor antagonist L741,626 but not by the selective D 3 receptor antagonist S33084 (Millan et al, 2000).…”

Functional‐anatomical Implications of the Nucleus Accumbens Core and Shell Subterritories

“…Injected individually, these agonists were ineffective at producing turning, and the effect was attenuated by injection of SCH‐23390 (D 1 antagonist) or l‐sulpiride (D 2 antagonist). Additional study 78,79 revealed that injections of D1 (SKF 82958) and D3 (7‐OH‐DPAT) receptor agonists also produced contralateral turns and jaw movements when injected together into shell (see also refs. 80 and 81).…”