The putative dopamine D3 agonist, 7-OH-DPAT, reduces dopamine release in the nucleus accumbens and electrical self-stimulation to the ventral tegmentum

Brain Res. 1995 May 29;681(1-2):1-7. doi: 10.1016/0006-8993(95)00247-n.

Abstract

The present experiments were designed to test further the idea that 7-OH-DPAT (7-hydroxy-N,N-di-n-propyl-2-aminotetralin), a putative dopamine (DA) D3 agonist, has effects at DA autoreceptors to reduce intracranial DA levels and to reduce behaviours that are DA-dependent. Rats were trained to respond on a self-stimulation protocol for electrical stimulation to the ventral tegmental area (VTA). Each press of a lever delivered a 0.5 s train of square wave, 1.5 ms duration, 100 Hz, 90-120 mA stimulation. Systemic administration of 7-OH-DPAT at 0.01-0.3 mg/kg i.p., quickly dose-dependently reduced responding. Electrical stimulation using similar parameters to those that supported self-stimulation were then applied to the VTA of anaesthetized rats. Fast cyclic voltammetry (FCV) revealed that this stimulation released DA in the nucleus accumbens (NAC). 7-OH-DPAT i.p. (0.1-3.0 mg/kg) quickly and potently reduced the size of the DA-generated voltammetric signal. This effect of 0.3 mg/kg 7-OH-DPAT was not blocked by sulpiride (60 mg/kg, i.p.) a D2-specific antagonist that may preferentially block D2 autoreceptors. These data are discussed with reference to the possibility that 7-OH-DPAT reduces the release of dopamine in the NAC, at D3, but not at D2, autoreceptors and that this in turn may reduce the rewarding effect of VTA stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopamine / metabolism*
  • Dopamine Agonists / pharmacology*
  • Dopamine Antagonists / pharmacology
  • Electric Stimulation
  • Electrodes, Implanted
  • Female
  • Male
  • Nucleus Accumbens / anatomy & histology
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism*
  • Rats
  • Receptors, Dopamine / drug effects*
  • Receptors, Dopamine D2*
  • Receptors, Dopamine D3
  • Self Stimulation
  • Sulpiride / pharmacology
  • Tetrahydronaphthalenes / pharmacology*
  • Ventral Tegmental Area / anatomy & histology
  • Ventral Tegmental Area / physiology*

Substances

  • Dopamine Agonists
  • Dopamine Antagonists
  • Drd3 protein, rat
  • Receptors, Dopamine
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Tetrahydronaphthalenes
  • Sulpiride
  • 7-hydroxy-2-N,N-dipropylaminotetralin
  • Dopamine