Source Paper
Rewarding Actions of Phencyclidine and Related Drugs in Nucleus Accumbens Shell and Frontal Cortex
William A. Carlezon,, Roy A. Wise
Journal of Neuroscience • 1996
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Protocol Steps
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Establish lever-pressing behavior with PCP reinforcement
Rats learn to lever-press when behavior is reinforced by microinjections of phencyclidine directly into the ventromedial (shell) region of nucleus accumbens
Note: This demonstrates PCP has direct rewarding actions in nucleus accumbens shell
View evidence from paper
“Rats learned to lever-press when such behavior was reinforced by microinjections of phencyclidine (PCP) directly into the ventromedial (shell) region of nucleus accumbens”
Test MK-801 reinforcement in nucleus accumbens shell
Separate group of rats learns to lever-press when reinforced with microinjections of dizocilpine (MK-801) into nucleus accumbens shell
Note: MK-801 blocks NMDA receptor function but not dopamine uptake
View evidence from paper
“Separate groups of rats learned to lever-press when reinforced with microinjections of dizocilpine (MK-801)”
Test CPP reinforcement in nucleus accumbens shell
Separate group of rats learns to lever-press when reinforced with microinjections of CPP into nucleus accumbens shell
Note: CPP blocks NMDA receptor function but not dopamine uptake
View evidence from paper
“Separate groups of rats learned to lever-press when reinforced with microinjections of dizocilpine (MK-801) or 3-((±)2-carboxypiperazin-4yl)propyl-1-phosphate (CPP)”
Test drug effectiveness at dorsal and lateral nucleus accumbens core site
Test PCP, MK-801, and CPP at a slightly more dorsal and lateral site in the core of nucleus accumbens to determine regional specificity
Note: Each drug was ineffective or markedly less effective at this site compared to shell
View evidence from paper
“Each drug was ineffective or markedly less effective when injected at a slightly more dorsal and lateral site in the core of nucleus accumbens”
Test dopamine-dependence with sulpiride co-infusion
Co-infuse sulpiride (dopamine antagonist) with PCP, MK-801, or CPP into nucleus accumbens to test if rewarding actions are dopamine-dependent
Note: Sulpiride dose was effective at blocking nomifensine self-administration but did not alter NMDA antagonist self-administration
View evidence from paper
“Self-administration of PCP, MK-801, or CPP directly into nucleus accumbens was not altered by co-infusion of a dose of the dopamine antagonist sulpiride that effectively blocked intracranial self-administration of the dopamine uptake inhibitor nomifensine”
Test PCP, MK-801, and CPP reinforcement in frontal cortex
Rats develop lever-pressing habits when PCP, MK-801, and CPP are each microinjected directly into frontal cortex
Note: Frontal cortex is a region previously associated with rewarding actions of cocaine but not nomifensine
View evidence from paper
“Rats also developed lever-pressing habits when PCP, MK-801, and CPP were each microinjected directly into frontal cortex”