Repeated injections of sulpiride into the medial prefrontal cortex induces sensitization to cocaine in rats
by
Steketee JD, Walsh TJ.
Department of Pharmacology,
University of Tennessee Health Science Center,
874 Union Avenue/Room 115 Crowe,
Memphis, 38163, TN, USA,
jsteketee@utmem.edu.
Psychopharmacology (Berl). 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.

Sulpiride
Sensitisation
The pleasure centres
The nucleus accumbens
Dopamine/D1receptors
Dopamine/D2 receptors
Dopamine/D3 receptors
Dopamine/D4 receptors

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