Jeffery D Steketee1, Timothy J Walsh. 1. Department of Pharmacology, University of Tennessee Health Science Center, 874 Union Avenue/Room 115 Crowe, Memphis, TN 38163, USA. jsteketee@utmem.edu
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.
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.
Authors: M Scott Bowers; Krista McFarland; Russell W Lake; Yuri K Peterson; Christopher C Lapish; Mary Lee Gregory; Stephen M Lanier; Peter W Kalivas Journal: Neuron Date: 2004-04-22 Impact factor: 17.173
Authors: Catharine A Winstanley; Thomas A Green; David E H Theobald; William Renthal; Quincey LaPlant; Ralph J DiLeone; Sumana Chakravarty; Eric J Nestler Journal: Pharmacol Biochem Behav Date: 2008-12-16 Impact factor: 3.533