Pregabalin: Potential for Addiction and a Possible Glutamatergic Mechanism

Althobaiti, Yusuf S.; Almalki, Atiah H.; Alsaab, Hashem O.; Alsanie, Walaa F.; Gaber, Ahmed; Alhadidi, Qasim; Hardy, Ana Maria Gregio; Nasr, Abdulrahman; Alzahrani, Omar; Stary, Creed M.; Shah, Zahoor A.

doi:10.1038/s41598-019-51556-4

Cited by 20 publications

(29 citation statements)

References 64 publications

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“…On day 3, mouse movement in the two chambers was recorded (pretest) and the time spent in each chamber was calculated using the ANY-maze software (Stoelting, USA). An unbiased CPP design was followed and, to eliminate possible bias to any chamber, mice spending >67% of the total time in any one chamber were excluded from the study [45][46][47]. Moreover, half of the animals were randomly assigned to receive quetiapine in chamber 1 and the remaining half received it in chamber 2.…”

Section: Cpp Paradigmmentioning

confidence: 99%

Quetiapine-Induced Place Preference in Mice: Possible Dopaminergic Pathway

Althobaiti

2021

Pharmaceuticals

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Quetiapine, an atypical antipsychotic, is effective in the management of schizophrenia, depression, and anxiety. Although quetiapine overdosage and misuse have been reported, its abuse potential has not been investigated in animals. In this study, the abuse potential of quetiapine was assessed based on the conditioned place preference (CPP) paradigm of drug addiction in a mouse model. First, mice received intraperitoneal injections of quetiapine (40, 80, or 120 mg/kg) every other day during the conditioning phase. In the second experiment, mice were pretreated with 0.03 mg/kg SKF-35866, a D1 receptor antagonist, before receiving saline or quetiapine (120 mg/kg) during the conditioning phase. No significant changes in time spent in the quetiapine-paired chamber were observed compared with time spent in the saline-paired chamber in mice treated with 40 or 80 mg/kg. In contrast, the preference to the quetiapine-paired chamber was significantly increased in mice treated with 120 mg/kg quetiapine, and this effect was blocked by SKF-35866 pretreatment. These results demonstrated, for the first time, the abuse potential of quetiapine in an animal model of drug addiction. Interestingly, this CPP-inducing effect was likely mediated by activating D1 receptors.

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Section: Cpp Paradigmmentioning

confidence: 99%

Quetiapine-Induced Place Preference in Mice: Possible Dopaminergic Pathway

Althobaiti

2021

Pharmaceuticals

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“…× 4). This dose of pregabalin was selected because it induced place preference in a previous study [13]. Moreover, pregabalin at low doses (30 mg/kg) or less is less effective than high doses are, which were reported in numerous case studies in inducing rewarding effects [44][45][46][47][48].…”

Section: Experimental Designmentioning

confidence: 99%

“…The CPP apparatus was produced from acrylic material. The apparatus contained two conditioning compartments that were identical in size (35 × 35 × 50 cm), and one external start box (10 × 15 × 10 cm) as previously explained [13]. Compartments were marked with distinctive visual and tactile cues.…”

Section: Cpp Model Apparatusmentioning

confidence: 99%

“…High doses and extended use of Healthcare 2021, 9, 376 2 of 11 pregabalin were reported to be associated with euphoria and withdrawal symptoms [9][10][11][12]. Althobaiti et al showed that pregabalin induced conditioned place preference (CPP) and might affect the glutamatergic mechanism when used at doses of 60-90 mg/kg [13]. It is essential that the mechanisms by which pregabalin induces rewarding effects are further understood.…”

Section: Introductionmentioning

confidence: 99%

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Potential Benefits of N-Acetylcysteine in Preventing Pregabalin-Induced Seeking-Like Behavior

et al. 2021

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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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“…Despite many advantages of using pregabalin for pain treatment, its side effects remain a concern. A study in mice found that pregabalin can cause development of dependence by modulating the glutamatergic system [ 15 ]. For some instances, pregabalin causes rashes, weight gain, dry mouth, dizziness, and heart failure [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Co-administration of Pregabalin and Curcumin Synergistically Decreases Pain-Like Behaviors in Acute Nociceptive Pain Murine Models

et al. 2020

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Analgesic drugs in a combination-form can achieve greater efficacy with lesser side effects compared to either drug alone. The combination of drugs acting at different targets or mechanisms of action has been recognized as an alternative approach for achieving optimal analgesia. In this study, the analgesic effects of pregabalin (30, 60, 100, 200 mg/kg), curcumin (15, 30, 60, 100, 120 mg/kg), and 1:1 fixed-dose ratio of the pregabalin-curcumin combination were assessed using two acute nociceptive pain models, the acetic acid-induced writhing and tail-flick tests in mice. The pregabalin-curcumin combination produced a dose-dependent decrease in mean of writhes and an increase in the percentage of antinociception by the acetic acid-induced writhing test. In the tail-flick test, the combination also showed an improvement in antinociception indicated by the tail-flick latency, % antinociception, and area under the curve (AUC). Isobolographic analysis of interactions demonstrated a significant synergistic interaction effect between pregabalin and curcumin in both acute nociceptive pain models with the experimental ED50 below the predicted additive line and the combination index < 1. These findings demonstrate that the combination of pregabalin and curcumin exhibits a synergistic interaction in mouse models of acute nociceptive pain.

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Pregabalin: Potential for Addiction and a Possible Glutamatergic Mechanism

Cited by 20 publications

References 64 publications

Quetiapine-Induced Place Preference in Mice: Possible Dopaminergic Pathway

Quetiapine-Induced Place Preference in Mice: Possible Dopaminergic Pathway

Potential Benefits of N-Acetylcysteine in Preventing Pregabalin-Induced Seeking-Like Behavior

Co-administration of Pregabalin and Curcumin Synergistically Decreases Pain-Like Behaviors in Acute Nociceptive Pain Murine Models

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