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

Eur J Pharmacol. 1996 Jul 25;308(3):235-41. doi: 10.1016/0014-2999(96)00302-0.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
  • Animals
  • Behavior, Animal / drug effects*
  • Benzazepines / pharmacology
  • Benzopyrans / pharmacology
  • Domperidone / pharmacology
  • Dopamine Agonists / pharmacology
  • Dopamine Antagonists / pharmacology
  • Male
  • Movement / drug effects*
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Oxazines / pharmacology
  • Quinpirole / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D2 / agonists*
  • Sulpiride / pharmacology
  • Tetrahydronaphthalenes / pharmacology*

Substances

  • Benzazepines
  • Benzopyrans
  • Dopamine Agonists
  • Dopamine Antagonists
  • Oxazines
  • Receptors, Dopamine D2
  • Tetrahydronaphthalenes
  • 3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol
  • Quinpirole
  • Domperidone
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • Sulpiride
  • 7-hydroxy-2-N,N-dipropylaminotetralin