Abstract
Morphine is one kind of opioid, which is currently the most effective widely utilized pain relieving pharmaceutical. Long-term administration of morphine leads to dependence and addiction. Thioredoxin-1 (Trx-1) is an important redox regulating protein and works as a neurotrophic cofactor. Our previous study showed that geranylgeranylaceton, an inducer of Trx-1 protected mice from rewarding effects induced by morphine. However, whether overexpression of Trx-1 can block morphine-induced conditioned place preference (CPP) in mice is still unknown. In this study, we first examined whether overexpression of Trx-1 affects the CPP after morphine training and further examined the dopamine (DA) and γ-aminobutyric acid (GABA) systems involved in rewarding effects. Our results showed that morphine-induced CPP was blocked in Trx-1 overexpression transgenic (TG) mice. Trx-1 expression was induced by morphine in the ventral tegmental area (VTA) and nucleus accumbens (NAc) in wild-type (WT) mice, which was not induced in Trx-1 TG mice. The DA level and expressions of tyrosine hydroxylase (TH) and D1 were induced by morphine in WT mice, which were not induced in Trx-1 TG mice. The GABA level and expression of GABABR were decreased by morphine, which were restored in Trx-1 TG mice. Therefore, Trx-1 may play a role in blocking CPP induced by morphine through regulating the expressions of D1, TH, and GABABR in the VTA and NAc.
Highlights
Morphine is the most effective pain relieving pharmaceutical, which repeated use can lead to dependence and addiction
The results showed that conditioned place preference (CPP) was induced after morphine treatment in WT mice, while the CPP was not induced by morphine in Trx-1 TG mice (Figure 2)
We found that overexpression of Trx-1 blocked morphine-induced CPP (Figure 2)
Summary
Morphine is the most effective pain relieving pharmaceutical, which repeated use can lead to dependence and addiction. Whether Trx-1 TG mice resist the rewarding effects induced by morphine is still unknown. We examined conditioned place preference (CPP) in both wild-type (WT) mice and Trx-1 TG mice after morphine conditioned training and detected the levels of DA and GABA and the expressions of tyrosine hydroxylase (TH), D1, and GABA receptor B (GABABR) in the VTA and NAc. Morphine hydrochloride was obtained from Shenyang First Phar maceutical Factory, Northeast Pharmaceutical Group Corp. On days 4, 6, 8, and 10, mice received a morphine injection (20 mg/kg) and were immediately placed into the appropriate chamber (morphine-paired chamber) of the CPP box for 15 min. On day 12, the post-conditioning test was performed without drug treatment, and the time when the mice spent in each chamber was measured for 15 min and time spent in each chamber was evaluated to determine preference. A P value less than 0.05 was considered statistically significant
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