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Formation of aversive memories associated with conditioned drug withdrawal requires BDNF expression in the amygdala in acute morphine-dependent rats.

Ju YY, Long JD, Liu Y, Liu JG - Acta Pharmacol. Sin. (2015)

Bottom Line: Brain-derived neurotrophic factor (BDNF) plays an important role in learning and memory in multiple brain areas.BDNF mRNA and protein expression levels in amygdala were detected after the behavior testing.CPA behavior was induced in rats by the naloxone-precipitated morphine withdrawal, which was accompanied by significantly increased levels of BDNF mRNA and protein in the amygdala.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

ABSTRACT

Aim: Brain-derived neurotrophic factor (BDNF) plays an important role in learning and memory in multiple brain areas. In the present study, we investigated the roles of BDNF in aversive memories associated with conditioned drug withdrawal in acute morphine-dependent rats.

Methods: Conditioned place aversion (CPA) was induced in male SD rats exposed to a single dose of morphine (10 mg/kg, sc) followed by naloxone (0.3 mg/kg, sc). In some rats, BDNF receptor antagonist K252a (8.5 ng per side) or BDNF scavenger TrkB-FC (0.65 μg per side) was bilaterally microinjected into amygdala before naloxone injection. BDNF mRNA and protein expression levels in amygdala were detected after the behavior testing.

Results: CPA behavior was induced in rats by the naloxone-precipitated morphine withdrawal, which was accompanied by significantly increased levels of BDNF mRNA and protein in the amygdala. Bilateral microinjection of TrkB-FC or K252a into the amygdala completely blocked CPA behavior in the rats.

Conclusion: Formation of aversive memories associated with conditioned drug withdrawal in acute morphine-dependent rats requires BDNF expression in the amygdala.

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Related in: MedlinePlus

Place aversion was induced by conditioned naloxone-precipitated drug withdrawal in the rats exposed to a single dose of morphine. Mean±SEM. cP<0.01 vs the saline-treated control group. Two-tailed Student's t-test. CMW: conditioned morphine withdrawal.
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fig1: Place aversion was induced by conditioned naloxone-precipitated drug withdrawal in the rats exposed to a single dose of morphine. Mean±SEM. cP<0.01 vs the saline-treated control group. Two-tailed Student's t-test. CMW: conditioned morphine withdrawal.

Mentions: We first established a stable rat CPA model. Previous studies have found that significant place aversion can be conditioned by naloxone-precipitated withdrawal after either acute or chronic morphine injections26,27,28. In our study, we used a training paradigm in which CPA was induced by naloxone (0.3 mg/kg, sc) 4 h after a single exposure to morphine (10 mg/kg, sc), and the rats were subsequently confined to the drug-paired compartment for 30 min. Consistent with previous studies, conditioned morphine withdrawal (CMW) produced significant aversion score compared with the saline-paired control group (aversion scores: Con, −38.67±58.39 s, n=8; CMW, −298.7±33.23 s, n=13) as shown in Figure 1. Two-tailed Student's t-tests showed that there was a significant difference between the two groups (t(19)=4.186, P<0.01). Our previous studies have also found that rats pretreated with morphine and subsequently exposed to a single pairing with saline (mor/sal) and rats pretreated with saline and subsequently exposed to a single pairing with naloxone (sal/nal) do not exhibit significant place aversions compared with saline-saline paired control groups; these findings indicate that morphine or naloxone injections alone cannot induce CPA10. Thus, we explored the molecular mechanism underlying the aversive memories of acute drug withdrawal on the basis of this CPA paradigm.


Formation of aversive memories associated with conditioned drug withdrawal requires BDNF expression in the amygdala in acute morphine-dependent rats.

Ju YY, Long JD, Liu Y, Liu JG - Acta Pharmacol. Sin. (2015)

Place aversion was induced by conditioned naloxone-precipitated drug withdrawal in the rats exposed to a single dose of morphine. Mean±SEM. cP<0.01 vs the saline-treated control group. Two-tailed Student's t-test. CMW: conditioned morphine withdrawal.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4816238&req=5

fig1: Place aversion was induced by conditioned naloxone-precipitated drug withdrawal in the rats exposed to a single dose of morphine. Mean±SEM. cP<0.01 vs the saline-treated control group. Two-tailed Student's t-test. CMW: conditioned morphine withdrawal.
Mentions: We first established a stable rat CPA model. Previous studies have found that significant place aversion can be conditioned by naloxone-precipitated withdrawal after either acute or chronic morphine injections26,27,28. In our study, we used a training paradigm in which CPA was induced by naloxone (0.3 mg/kg, sc) 4 h after a single exposure to morphine (10 mg/kg, sc), and the rats were subsequently confined to the drug-paired compartment for 30 min. Consistent with previous studies, conditioned morphine withdrawal (CMW) produced significant aversion score compared with the saline-paired control group (aversion scores: Con, −38.67±58.39 s, n=8; CMW, −298.7±33.23 s, n=13) as shown in Figure 1. Two-tailed Student's t-tests showed that there was a significant difference between the two groups (t(19)=4.186, P<0.01). Our previous studies have also found that rats pretreated with morphine and subsequently exposed to a single pairing with saline (mor/sal) and rats pretreated with saline and subsequently exposed to a single pairing with naloxone (sal/nal) do not exhibit significant place aversions compared with saline-saline paired control groups; these findings indicate that morphine or naloxone injections alone cannot induce CPA10. Thus, we explored the molecular mechanism underlying the aversive memories of acute drug withdrawal on the basis of this CPA paradigm.

Bottom Line: Brain-derived neurotrophic factor (BDNF) plays an important role in learning and memory in multiple brain areas.BDNF mRNA and protein expression levels in amygdala were detected after the behavior testing.CPA behavior was induced in rats by the naloxone-precipitated morphine withdrawal, which was accompanied by significantly increased levels of BDNF mRNA and protein in the amygdala.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

ABSTRACT

Aim: Brain-derived neurotrophic factor (BDNF) plays an important role in learning and memory in multiple brain areas. In the present study, we investigated the roles of BDNF in aversive memories associated with conditioned drug withdrawal in acute morphine-dependent rats.

Methods: Conditioned place aversion (CPA) was induced in male SD rats exposed to a single dose of morphine (10 mg/kg, sc) followed by naloxone (0.3 mg/kg, sc). In some rats, BDNF receptor antagonist K252a (8.5 ng per side) or BDNF scavenger TrkB-FC (0.65 μg per side) was bilaterally microinjected into amygdala before naloxone injection. BDNF mRNA and protein expression levels in amygdala were detected after the behavior testing.

Results: CPA behavior was induced in rats by the naloxone-precipitated morphine withdrawal, which was accompanied by significantly increased levels of BDNF mRNA and protein in the amygdala. Bilateral microinjection of TrkB-FC or K252a into the amygdala completely blocked CPA behavior in the rats.

Conclusion: Formation of aversive memories associated with conditioned drug withdrawal in acute morphine-dependent rats requires BDNF expression in the amygdala.

Show MeSH
Related in: MedlinePlus