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Neurochemical evidence that postsynaptic nucleus accumbens D3 receptor stimulation enhances cocaine reinforcement

Academic Article
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Overview

authors

  • Parsons, Loren (Larry)
  • Caine, S. B.
  • Sokoloff, P.
  • Schwartz, J. C.
  • Koob, George
  • Weiss, Friedbert

publication date

  • 1996

journal

  • Journal of Neurochemistry  Journal

abstract

  • The mechanism by which two D3 receptor-preferring agonists, 7-hydroxydipropylaminotetralin (7-OH-DPAT) and quinelorane, modulate cocaine reinforcement was examined by monitoring nucleus accumbens dopamine levels with in vivo microdialysis while rats intravenously self-administered the following four different drug solutions consecutively: (1) cocaine; (2) a combination of cocaine plus a low dose of either agonist; (3) either agonist alone; and finally, (4) a physiological saline solution. Both 7-OH-DPAT (4 micrograms/infusion) and quinelorane (0.25 microgram/infusion) decreased cocaine (0.25 mg/infusion) intake in a manner indicating an enhancement of cocaine reinforcement and simultaneously decreased the cocaine-induced elevations in nucleus accumbens dopamine levels by > 50%. Subsequent self-administration of either 7-OH-DPAT (4 micrograms/infusion) or quinelorane (0.25 microgram/infusion) alone resulted in significant, but stable, increases in drug intake, with a concurrent decrease in nucleus accumbens dopamine levels to approximately 50% below nondrug baseline levels. These findings indicate that postsynaptic D3 receptor stimulation in the nucleus accumbens enhances the reinforcing properties of cocaine. In a second experiment, local application of 7-OH-DPAT via reverse dialysis (30 and 100 nM perfusate concentrations) dose-dependently decreased nucleus accumbens dopamine efflux to 76 +/- 3.9 and 61 +/- 6.3% of baseline, respectively, whereas there was no effect of this agonist on dopamine efflux in the ipsilateral striatum of these same animals. Coperfusion with the D3 receptor-preferring antagonist nafadotride dose-dependently blocked the effect of 7-OH-DPAT on nucleus accumbens dopamine efflux. These results suggest that, at low concentrations, 7-OH-DPAT selectively activates D3 receptors in vivo.

subject areas

  • Animals
  • Cocaine
  • Dopamine
  • Dopamine Agonists
  • Dopamine Antagonists
  • Dopamine D2 Receptor Antagonists
  • Male
  • Microdialysis
  • Naphthalenes
  • Neostriatum
  • Nucleus Accumbens
  • Pyrrolidines
  • Quinolines
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Self Administration
  • Tetrahydronaphthalenes
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Identity

International Standard Serial Number (ISSN)

  • 0022-3042

Digital Object Identifier (DOI)

  • 10.1046/j.1471-4159.1996.67031078.x

PubMed ID

  • 8752115
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Additional Document Info

start page

  • 1078

end page

  • 1089

volume

  • 67

issue

  • 3

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