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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

CPA behavior can be inhibited by intra-amygdala micro-injection of TrkB inhibitor K252a. (A) Intra-amygdala microinjection of K252a blocked the formation of CPA behavior. (B) Schematic representation of injection sites of rats used in the experiment. ▴Vehicle; •K252a. Mean±SEM. bP<0.05 vs vehicle. Two-tailed Student's t-test.
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fig3: CPA behavior can be inhibited by intra-amygdala micro-injection of TrkB inhibitor K252a. (A) Intra-amygdala microinjection of K252a blocked the formation of CPA behavior. (B) Schematic representation of injection sites of rats used in the experiment. ▴Vehicle; •K252a. Mean±SEM. bP<0.05 vs vehicle. Two-tailed Student's t-test.

Mentions: To validate the role of BDNF, we used the BDNF receptor TrkB inhibitor K252a, which is a tyrosine kinase inhibitor with a high affinity for all Trk receptors, to block BDNF signaling and to observe its effect on the formation of CPA behavior. Ten minutes before naloxone pairing, either K252a (8.5 ng/0.5 μL per side) or vehicle was micro-injected into the rats' amygdala. As shown in Figure 3A, K252a significantly blocked the formation of CPA behavior compared with the solvent-injected control group. Two-tailed Student's t-test analyses revealed that there was a significant difference between the vehicle and K252a groups (Figure 3A, aversion scores: Vehicle, −331.7±84.45 s, n=6; K252a, −111.8±26.81 s, n=6; t(10)=2.482, P<0.05). Figure 3B illustrates the location of the microinjection tips in the rat amygdala in the present experiment. These data indicated that the BDNF signaling pathway indeed participates in aversive memory formation.


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)

CPA behavior can be inhibited by intra-amygdala micro-injection of TrkB inhibitor K252a. (A) Intra-amygdala microinjection of K252a blocked the formation of CPA behavior. (B) Schematic representation of injection sites of rats used in the experiment. ▴Vehicle; •K252a. Mean±SEM. bP<0.05 vs vehicle. Two-tailed Student's t-test.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: CPA behavior can be inhibited by intra-amygdala micro-injection of TrkB inhibitor K252a. (A) Intra-amygdala microinjection of K252a blocked the formation of CPA behavior. (B) Schematic representation of injection sites of rats used in the experiment. ▴Vehicle; •K252a. Mean±SEM. bP<0.05 vs vehicle. Two-tailed Student's t-test.
Mentions: To validate the role of BDNF, we used the BDNF receptor TrkB inhibitor K252a, which is a tyrosine kinase inhibitor with a high affinity for all Trk receptors, to block BDNF signaling and to observe its effect on the formation of CPA behavior. Ten minutes before naloxone pairing, either K252a (8.5 ng/0.5 μL per side) or vehicle was micro-injected into the rats' amygdala. As shown in Figure 3A, K252a significantly blocked the formation of CPA behavior compared with the solvent-injected control group. Two-tailed Student's t-test analyses revealed that there was a significant difference between the vehicle and K252a groups (Figure 3A, aversion scores: Vehicle, −331.7±84.45 s, n=6; K252a, −111.8±26.81 s, n=6; t(10)=2.482, P<0.05). Figure 3B illustrates the location of the microinjection tips in the rat amygdala in the present experiment. These data indicated that the BDNF signaling pathway indeed participates in aversive memory formation.

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