Involvement of the dopaminergic system in the reward-related behavior of pregabalin

Abstract

There has been an increase in cases of drug addiction and prescription drug abuse worldwide. Recently, pregabalin abuse has been a focus for many healthcare agencies, as highlighted by epidemiological studies. We previously evaluated the possibility of pregabalin abuse using the conditioned place preference (CPP) paradigm. We observed that a 60 mg/kg dose could induce CPP in mice and that pregabalin-rewarding properties were mediated through glutamate neurotransmission. Notably, the dopaminergic reward circuitry is also known to play a crucial role in medication-seeking behavior. Therefore, this study aimed to explore the possible involvement of dopaminergic receptor-1 in pregabalin-induced CPP. Mice were randomly allocated to receive saline or the dopamine-1 receptor antagonist SKF-83566 (0.03 mg/kg, intraperitoneal). After 30 min, the mice received either saline or pregabalin (60 mg/kg) during the conditioning phase. Among the control groups that received saline or SKF-83566, the time spent in the two conditioning chambers was not significantly altered. However, among the pregabalin-treated group, there was a marked increase in the time spent in the drug-paired chamber compared to the time spent in the vehicle-paired chamber. Notably, blocking dopamine-1 receptors with SKF-83566 completely prevented pregabalin-induced place preference, thus demonstrating the engagement of the dopaminergic system in pregabalin-induced reward-related behavior.

The Effects of Prenatal Exposure to Pregabalin on the Development of Ventral Midbrain Dopaminergic Neurons

“…This neuronal population is important for behavior, cognition, and motor activity. Our previous study suggested that the dopaminergic system could be affected by pregabalin administration [ 10 ]. In the present study, we identified that pregabalin at therapeutic doses (10 μM) had no impact on the survivability of neurons [ 29 ].…”

“…It is still unclear whether pregabalin at therapeutic doses causes abnormalities in the fetus and hampers its development [ 9 ]. Previously, we showed that pregabalin induces behavioral sensitization through the dopamine reward system, which suggests that pregabalin could have an effect on dopaminergic neurons [ 10 ].…”

The association between Gabapentin or Pregabalin use and the risk of dementia: an analysis of the National Health Insurance Research Database in Taiwan

“…These drugs not only block the development of hyperalgesia and central sensitization, but also inhibit the release of excitatory neurotransmitter, including glutamate, norepinephrine (noradrenaline), serotonin, and dopamine ( Hendrich et al, 2008 ; Eroglu et al, 2009 ). The dopamine reward system may play a role in gabapentinoid abuse and addiction ( Althobaiti et al, 2021 ). The hippocampus, with abundant alpha - 2 / delta-1 subunit of voltage-gated calcium channels, plays an essential role in processing declarative memories and working memory ( Yonelinas, 2013 ).…”

Prenatal Exposure to Gabapentin Alters the Development of Ventral Midbrain Dopaminergic Neurons

“…Similar to the other neural populations, VM neurons are known to have early and late developmental stages. Our recent investigation hypothesized that gabapentinoids could affect the dopaminergic neuronal system ( Althobaiti et al, 2020 , 2021 ). In the current study, we observed that gabapentin at therapeutic doses has no impact on the survivability of VM neurons.…”