Facilitation of morphine withdrawal symptoms and morphine-induced conditioned place preference by a glutamate transporter inhibitor dl-threo-β-benzyloxyaspartate in rats

Substance-use disorder is globally prevalent and responsible for numerous social and medical problems. Pregabalin (Lyrica), typically used to treat diabetic neuropathy, has recently emerged as a drug of abuse. Drug abuse is associated with several neuronal changes, including the downregulation of glutamate transporters such as glutamate transporter 1 and cystine/glutamate antiporter. We investigated the effects of N-acetylcysteine, a glutamate transporter 1 and xCT upregulator, on pregabalin addiction using a conditioned place preference paradigm. Pregabalin (60 mg/kg) was found to induce conditioned place preference when compared to a vehicle. A 100 mg/kg dose of N-acetylcysteine was found to block pregabalin-seeking behaviors. These results support previous findings showing that glutamate transporters play an important role in pregabalin-induced seeking behaviors. N-acetylcysteine may represent a beneficial agent in preventing the abuse potential of pregabalin.

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Pleiotrophin modulates morphine withdrawal but has no effects on morphine-conditioned place preference

Neuroscience Letters ◽

10.1016/j.neulet.2015.07.022 ◽

2015 ◽

Vol 604 ◽

pp. 75-79 ◽

Cited By ~ 6

Author(s):

Esther Gramage ◽

Marta Vicente-Rodríguez ◽

Gonzalo Herradón

Keyword(s):

Conditioned Place Preference ◽

Place Preference ◽

Morphine Withdrawal

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Effect of Chaihu-jia-Longgu-Muli decoction on withdrawal symptoms in rats with methamphetamine-induced conditioned place preference

Bioscience Reports ◽

10.1042/bsr20211376 ◽

2021 ◽

Author(s):

Zifa Li ◽

Yuchen Qi ◽

Kun Liu ◽

Yiming Cao ◽

Hao Zhang ◽

...

Keyword(s):

Body Weight ◽

Conditioned Place Preference ◽

Open Field Test ◽

Control Model ◽

Place Preference ◽

Withdrawal Symptoms ◽

Control Group ◽

Model Group ◽

Low Dosage ◽

Preference Experiment

Traditional Chinese medicine detoxification prescription Chaihu-jia-Longgu-Muli decoction (CLMD) relieves depressive symptoms in patients withdrawing from methamphetamine. In this study, we assessed the effects of CLMD on methamphetamine withdrawal in rats. A methamphetamine-intoxicated rat model was established. Rats were randomly divided into the control, model, high-dosage, medium-dosage, and low-dosage groups, receiving high, medium, and low doses of CLMD, respectively. Weekly body weight measurements revealed that rats treated with methamphetamine had the lowest body weight. The conditioned place preference experiment revealed that methamphetamine-intoxicated rats stayed significantly longer in the drug-paired chamber than the control rats. However, after administering high-dosage CLMD, the amount of time the rats spent in the drug-paired chamber was significantly less than that of the model rats. Our open-field test revealed that the model group had lower crossing and rearing scores than the control group. Additionally, rats that received CLMD treatment exhibited higher crossing and rearing scores than the model rats. Striatal DA, 5-HT, and β-EP and serum IL-1α and IL-2 concentrations were estimated. Rats in the model group had lower striatal DA, 5-HT, and β-EP and higher serum IL-1α and IL-2 concentrations than those in the control group. High-dosage CLMD administration significantly changed the concentrations of these molecules, such that they approached normal concentrations. In general, CLMD could prevent the development of methamphetamine-induced withdrawal symptoms in rats by increasing the DA, 5-HT, and β-EP and lowering the IL-1α and IL-2 concentrations.

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Bulleyaconitine A Inhibits Morphine-Induced Withdrawal Symptoms, Conditioned Place Preference, and Locomotor Sensitization Via Microglial Dynorphin A Expression

Frontiers in Pharmacology ◽

10.3389/fphar.2021.620926 ◽

2021 ◽

Vol 12 ◽

Author(s):

Meng-Jing Zhao ◽

Mi-Ya Wang ◽

Le Ma ◽

Khalil Ali Ahmad ◽

Yong-Xiang Wang

Keyword(s):

Weight Loss ◽

Body Weight ◽

Conditioned Place Preference ◽

Body Weight Loss ◽

Place Preference ◽

Withdrawal Symptoms ◽

Fecal Excretion ◽

Locomotor Sensitization ◽

Potential Candidate ◽

Dynorphin A

Bulleyaconitine A (BAA), a C19-diterpenoid alkaloid, has been prescribed as a nonnarcotic analgesic to treat chronic pain over four decades in China. The present study investigated its inhibition in morphine-induced withdrawal symptoms, conditioned place preference (CPP) and locomotor sensitization, and then explored the underlying mechanisms of actions. Multiple daily injections of morphine but not BAA up to 300 μg/kg/day into mice evoked naloxone-induced withdrawal symptoms (i.e., shakes, jumps, genital licks, fecal excretion and body weight loss), CPP expression, and locomotor sensitization. Single subcutaneous BAA injection (30–300 μg/kg) dose-dependently and completely attenuated morphine-induced withdrawal symptoms, with ED50 values of 74.4 and 105.8 μg/kg in shakes and body weight loss, respectively. Subcutaneous BAA (300 μg/kg) also totally alleviated morphine-induced CPP acquisition and expression and locomotor sensitization. Furthermore, subcutaneous BAA injection also specifically stimulated dynorphin A expression in microglia but not astrocytes or neurons in nucleus accumbens (NAc) and hippocampal, measured for gene and protein expression and double immunofluorescence staining. In addition, subcutaneous BAA-inhibited morphine-induced withdrawal symptoms and CPP expression were totally blocked by the microglial metabolic inhibitor minocycline, dynorphin A antiserum, or specific KOR antagonist GNTI, given intracerebroventricularly. These results, for the first time, illustrate that BAA attenuates morphine-induced withdrawal symptoms, CPP expression, and locomotor sensitization by stimulation of microglial dynorphin A expression in the brain, suggesting that BAA may be a potential candidate for treatment of opioids-induced physical dependence and addiction.

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