Repeated injections of sulpiride into the medial prefrontal cortex induces sensitization to cocaine in rats

Psychopharmacology (Berl). 2005 Jun;179(4):753-60. doi: 10.1007/s00213-004-2102-5. Epub 2004 Dec 24.

Abstract

Rationale: Recent studies have suggested that the medial prefrontal cortex (mPFC) plays an important role in the development of sensitization to cocaine. In particular, a recent report proposed that sensitization is associated with a decreased dopamine D(2) receptor function in the mPFC. The present study was designed to further examine the involvement of mPFC dopamine D(2) receptors in cocaine sensitization.

Objectives: The experiments described below sought to determine the effects of acute or repeated intra-mPFC injections of the dopamine D(2) antagonist sulpiride on subsequent motor-stimulant and nucleus accumbens dopamine responses to cocaine.

Methods: Rats received bilateral cannulae implants above the ventral mPFC for microinjections and above the nucleus accumbens for in vivo microdialysis. Initial studies examined the effects of intra-mPFC sulpiride pretreatment on the acute motor-stimulant and nucleus accumbens dopamine responses to cocaine. Follow-up studies determined the effects of repeated intra-mPFC sulpiride injections on subsequent behavioral and nucleus accumbens dopamine responses to a cocaine challenge.

Results: Intra-mPFC sulpiride enhanced the cocaine-induced increases in motor activity and dopamine overflow in the nucleus accumbens. Repeated intra-mPFC sulpiride induced behavioral and neurochemical cross-sensitization to cocaine.

Conclusions: The data support previous findings that sensitization is associated with a decrease in dopamine D(2) receptor function in the mPFC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cocaine / pharmacology*
  • Dopamine / metabolism
  • Dopamine Antagonists / administration & dosage
  • Dopamine Antagonists / pharmacology*
  • Dopamine Uptake Inhibitors / pharmacology*
  • Drug Synergism
  • Male
  • Microinjections
  • Motor Activity / drug effects
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Prefrontal Cortex*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D2 / drug effects
  • Stimulation, Chemical
  • Sulpiride / administration & dosage
  • Sulpiride / pharmacology*

Substances

  • Dopamine Antagonists
  • Dopamine Uptake Inhibitors
  • Receptors, Dopamine D2
  • Sulpiride
  • Cocaine
  • Dopamine