Intracranial Self-Administration in Nucleus Accumbens Shell — William A. Carlezon, | ReplicateScience

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Intracranial Self-Administration in Nucleus Accumbens Shell — William A. Carlezon, | ReplicateScience

Protocol Steps

1

Surgical implantation of microinjection cannulae

Implant microinjection cannulae targeting the ventromedial (shell) region of nucleus accumbens in rats

Not specifiedNot specified

Note: Separate groups received implants targeting either nucleus accumbens shell or core, or frontal cortex

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

Operant conditioning training - PCP group

Train rats to lever-press with reinforcement of PCP microinjections into nucleus accumbens shell

Not specifiedNot specified

Note: Rats learned lever-pressing behavior when reinforced with drug microinjections

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”

3

Operant conditioning training - MK-801 group

Train separate group of rats to lever-press with reinforcement of MK-801 microinjections 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”

4

Operant conditioning training - CPP group

Train separate group of rats to lever-press with reinforcement of CPP microinjections 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), drugs known to block NMDA receptor function but not dopamine uptake”

5

Test drug effectiveness at nucleus accumbens core

Inject each drug (PCP, MK-801, CPP) at a slightly more dorsal and lateral site in the core of nucleus accumbens to test regional specificity

Not specifiedNot specified

Note: Each drug was ineffective or markedly less effective when injected at 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”

6

Test dopamine-dependence with sulpiride co-infusion

Co-infuse sulpiride (dopamine antagonist) with PCP, MK-801, or CPP into nucleus accumbens shell during self-administration sessions

Not specifiedNot specified

Note: Sulpiride dose was one that effectively blocked self-administration of nomifensine (dopamine uptake inhibitor)

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”

7

Test drug effects in frontal cortex

Microinject PCP, MK-801, and CPP directly into frontal cortex and measure lever-pressing behavior

Not specifiedNot specified

Note: Frontal cortex was 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”