Intracranial Self-Administration in Frontal Cortex — William A. Carlezon, | ReplicateScience

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Intracranial Self-Administration in Frontal Cortex — William A. Carlezon, | ReplicateScience

Protocol Steps

1

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

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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”

2

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

not specifiednot specified

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)”

3

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

not specifiednot specified

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)”

4

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

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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”

5

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

not specifiednot specified

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”

6

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

not specifiednot specified

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”