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Cocaine-Conditioned Place Preference — Jay P McLaughlin | ReplicateScience

Experiments/Cocaine-Conditioned Place Preference

Source Paper

Kappa opioid receptor antagonism and prodynorphin gene disruption block stress-induced behavioral responses.

Jay P McLaughlin, Monica Marton-Popovici, Charles Chavkin

PubMed • 2003

Cocaine-Conditioned Place Preference

behavioralmouseC57Bl/6

Objective: Assessment of cocaine reward by measuring preference for a drug-paired chamber in mice exposed to forced swim stress or control conditions, and to test whether stress-induced dynorphin release mediates stress-induced potentiation of cocaine reward

Materials & Equipment Checklist

5 items3 from ConductScience

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Equipment3

Forced Swim Test apparatus

Not specified • Not specified • Not specified • Not specified

Tail withdrawal latency assay apparatus

Not specified • Not specified • Not specified • Not specified

Conditioned Place Preference (CPP) apparatus

Not specified • Not specified • Not specified • Not specified

Materials2

nor-binaltorphimine (nor-BNI)

Not specified • Not specified • Not specified • Not specified

Cocaine

Not specified • Not specified • Not specified • Not specified

3 items available from ConductScience

Estimated: $1,290.00

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Protocol Steps

View Abstract

Previous studies have demonstrated that stress may increase prodynorphin gene expression, and kappa opioid agonists suppress drug reward. Therefore, we tested the hypothesis that stress-induced release of endogenous dynorphin may mediate behavioral responses to stress and oppose the rewarding effects of cocaine. C57Bl/6 mice subjected to repeated forced swim testing (FST) using a modified Porsolt procedure at 30 degrees C showed a characteristic stress-induced immobility response and a stress-induced analgesia observed with a tail withdrawal latency assay. Pretreatment with the kappa opioid receptor antagonist nor-binaltorphimine (nor-BNI; 10 mg/kg, i.p.) blocked the stress-induced analgesia and significantly reduced the stress-induced immobility. The nor-BNI sensitivity of the behavioral responses suggests an activation of the kappa opioid receptor by a stress-induced release of dynorphin peptides. Supporting this hypothesis, transgenic mice possessing a disrupted prodynorphin gene showed no increase in immobility or stress-induced analgesia after exposure to repeated FST. Because both stress and the kappa opioid system can modulate the response to drugs of abuse, we tested the effects of forced swim stress on cocaine-conditioned place preference (CPP). FST-exposed mice conditioned with cocaine (15 mg/kg, s.c.) showed significant potentiation of place preference for the drug-paired chamber over the responses of unstressed mice. Surprisingly, nor-BNI pretreatment blocked stress-induced potentiation of cocaine CPP. Consistent with this result, mice lacking the prodynorphin gene did not show a stress-induced potentiation of cocaine CPP, whereas wild-type littermates did. The findings suggest that chronic swim stress may activate the kappa opioid system to produce analgesia, immobility, and potentiation of the acute rewarding properties of cocaine in C57Bl/6 mice.

1

Forced Swim Stress Exposure

C57Bl/6 mice subjected to repeated forced swim testing using a modified Porsolt procedure

Not specified30°C

Forced Swim Test Apparatus

Note: This produces characteristic stress-induced immobility response and stress-induced analgesia

View evidence from paper

“C57Bl/6 mice subjected to repeated forced swim testing (FST) using a modified Porsolt procedure at 30°C showed a characteristic stress-induced immobility response”

2

Measurement of Stress-Induced Analgesia

Tail withdrawal latency assay performed to measure stress-induced analgesia

Not specifiedNot specified

Note: Used to assess analgesic response to stress

View evidence from paper

“stress-induced analgesia observed with a tail withdrawal latency assay”

3

nor-BNI Pretreatment (Experimental Group)

Pretreatment with κ opioid receptor antagonist nor-binaltorphimine administered intraperitoneally

Not specifiedNot specified

Note: Administered to test whether κ opioid receptor activation mediates stress responses

View evidence from paper

“Pretreatment with the κ opioid receptor antagonist nor-binaltorphimine (nor-BNI; 10 mg/kg, i.p.)”

4

Cocaine Conditioning

Mice conditioned with cocaine via subcutaneous injection

Not specifiedNot specified

Note: Cocaine dose 15 mg/kg administered subcutaneously during conditioning phase

View evidence from paper

“FST-exposed mice conditioned with cocaine (15 mg/kg, s.c.)”

5

Conditioned Place Preference Testing

Assessment of preference for the drug-paired chamber in stressed versus unstressed mice

Not specifiedNot specified

Conditioned Place Preference - Mouse (Custom Order)

Conditioned Place Preference - Mouse (Custom Order)

Matches: Conditioned Place Preference (CPP) apparatus

$1,290View

Note: Measures time spent in cocaine-paired chamber compared to control chamber

View evidence from paper

“FST-exposed mice conditioned with cocaine (15 mg/kg, s.c.) showed significant potentiation of place preference for the drug-paired chamber”

Subjects / Specimens

Species: mouse
Strain: C57Bl/6
Age: Not specified
Sex: unknown
Weight: Not specified

Transgenic mice with disrupted prodynorphin gene and wild-type littermates were also used