Dopamine Antagonist Co-infusion Self-Administration — William A. Carlezon, | ReplicateScience

ReplicateScience

Submit Paper ConductScience

Dopamine Antagonist Co-infusion Self-Administration — William A. Carlezon, | ReplicateScience

Protocol Steps

1

Establish lever-press self-administration with PCP in nucleus accumbens shell

Rats are trained to lever-press with reinforcement of microinjections of phencyclidine (PCP) directly into the ventromedial (shell) region of nucleus accumbens

Not specifiedNot specified

Note: This establishes that PCP has direct rewarding actions in the nucleus accumbens shell region

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

Establish lever-press self-administration with MK-801 in nucleus accumbens shell

Separate group of rats trained to lever-press with reinforcement of microinjections of dizocilpine (MK-801) directly 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) or 3-((±)2-carboxypiperazin-4yl)propyl-1-phosphate (CPP), drugs known to block NMDA receptor function but not dopamine uptake”

3

Establish lever-press self-administration with CPP in nucleus accumbens shell

Separate group of rats trained to lever-press with reinforcement of microinjections of 3-((±)2-carboxypiperazin-4yl)propyl-1-phosphate (CPP) directly into nucleus accumbens shell

Not specifiedNot specified

Conditioned Place Preference - Mouse (Custom Order)

Conditioned Place Preference - Mouse (Custom Order)

Matches: 3-((±)2-carboxypiperazin-4yl)propyl-1-phosphate (CPP)

$1,290View

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), drugs known to block NMDA receptor function but not dopamine uptake”

4

Test drug effectiveness at 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

Not specifiedNot specified

Note: Each drug was ineffective or markedly less effective at the core 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

Co-infuse sulpiride dopamine antagonist during NMDA antagonist self-administration

During self-administration of PCP, MK-801, or CPP into nucleus accumbens, co-infuse sulpiride at a dose that effectively blocks intracranial self-administration of nomifensine

Not specifiedNot specified

Note: Sulpiride dose is validated by its ability to block nomifensine self-administration. Self-administration of NMDA antagonists was not altered by sulpiride co-infusion

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 NMDA antagonist self-administration in frontal cortex

Rats are trained to lever-press 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, a region previously associated with the rewarding actions of cocaine but not nomifensine”