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
Source Paper
William A. Carlezon,, Roy A. Wise
Journal of Neuroscience • 1996
Rats learned to lever-press when such behavior was reinforced by microinjections of phencyclidine (PCP) directly into the ventromedial (shell) region of nucleus accumbens, indicating that the drug has direct rewarding actions in that region. 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), drugs known to block NMDA receptor function but not dopamine uptake, into the same region. Each drug was ineffective or markedly less effective when injected at a slightly more dorsal and lateral site in the core of nucleus accumbens. 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, suggesting that the rewarding actions of the NMDA receptor antagonists are not dopamine-dependent. Rats also developed lever-pressing habits when PCP, MK-801, and CPP were each microinjected directly into frontal cortex, a region previously associated with the rewarding actions of cocaine but not nomifensine. Thus nucleus accumbens and frontal cortex are each potential substrates for the rewarding properties of PCP and related drugs, and the ability of these drugs to disrupt NMDA receptor function seems sufficient to account for their rewarding actions. When considered with independent evidence, the present results suggest a model of drug reward within which the critical event is inhibition of medium spiny neurons in nucleus accumbens.
Objective: To assess regional specificity of drug reward by examining lever-pressing behavior reinforced by microinjections of NMDA receptor antagonists (PCP, MK-801, CPP) into nucleus accumbens core versus shell, and to determine whether rewarding actions are dopamine-dependent
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Rats are trained to lever-press with behavior reinforced by microinjections of phencyclidine (PCP) directly into the ventromedial (shell) region of nucleus accumbens
Note: This establishes that PCP has direct rewarding actions in the shell region
“Rats learned to lever-press when such behavior was reinforced by microinjections of phencyclidine (PCP) directly into the ventromedial (shell) region of nucleus accumbens”
Separate group of rats trained to lever-press when reinforced with microinjections of dizocilpine (MK-801) into the ventromedial (shell) region of nucleus accumbens
Note: MK-801 is an NMDA receptor antagonist that does not block dopamine uptake
“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), drugs known to block NMDA receptor function but not dopamine uptake, into the same region”
Separate group of rats trained to lever-press when reinforced with microinjections of CPP into the ventromedial (shell) region of nucleus accumbens
Note: CPP is an NMDA receptor antagonist that does not block dopamine uptake
“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), drugs known to block NMDA receptor function but not dopamine uptake, into the same region”
Test PCP microinjections at a slightly more dorsal and lateral site in the core of nucleus accumbens to assess regional specificity
Note: Each drug was ineffective or markedly less effective when injected at the core site compared to shell
“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 MK-801 microinjections at a slightly more dorsal and lateral site in the core of nucleus accumbens to assess regional specificity
Note: MK-801 was ineffective or markedly less effective when injected at the core site compared to shell
“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 CPP microinjections at a slightly more dorsal and lateral site in the core of nucleus accumbens to assess regional specificity
Note: CPP was ineffective or markedly less effective when injected at the core site compared to shell
“Each drug was ineffective or markedly less effective when injected at a slightly more dorsal and lateral site in the core of nucleus accumbens”
Co-infuse dopamine antagonist sulpiride (at a dose that effectively blocks nomifensine self-administration) with PCP, MK-801, or CPP microinjections into nucleus accumbens to determine if rewarding actions are dopamine-dependent
Note: Self-administration was not altered by sulpiride co-infusion, suggesting NMDA antagonist reward is not dopamine-dependent
“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”
Rats trained to lever-press when reinforced with microinjections of PCP directly into frontal cortex
Note: Frontal cortex is a region previously associated with rewarding actions of cocaine but not nomifensine
“Rats also developed lever-pressing habits when PCP, MK-801, and CPP were each microinjected directly into frontal cortex, a region previously associated with the rewarding actions of cocaine but not nomifensine”
Rats trained to lever-press when reinforced with microinjections of MK-801 directly into frontal cortex
Note: Frontal cortex is a region previously associated with rewarding actions of cocaine but not nomifensine
“Rats also developed lever-pressing habits when PCP, MK-801, and CPP were each microinjected directly into frontal cortex, a region previously associated with the rewarding actions of cocaine but not nomifensine”
Rats trained to lever-press when reinforced with microinjections of CPP directly into frontal cortex
Note: Frontal cortex is a region previously associated with rewarding actions of cocaine but not nomifensine
“Rats also developed lever-pressing habits when PCP, MK-801, and CPP were each microinjected directly into frontal cortex, a region previously associated with the rewarding actions of cocaine but not nomifensine”
Multiple groups tested with different drug conditions
Evidence-Based
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