Abstract：
:Drug addiction remains a prevalent and fatal disease worldwide that carries significant social and economic impacts. Recent reports suggest illicit pregabalin (Lyrica) use may be increasing among youth, however the addictive potential of pregabalin has not been well established. Drug seeking behavior and chronic drug use are associated with deficits in glutamate clearance and activation of postsynaptic glutamatergic receptors. In the current study, we investigated the abuse potential of pregabalin using conditioned place preference (CPP) paradigm. Different doses of pregabalin (30, 60, 90, and 120 mg/kg) were used to assess the seeking behavior in mice. Glutamate homeostasis is maintained by glutamate transporter type-1 (GLT-1), which plays a vital role in clearing the released glutamate from synapses and drug seeking behavior. Therefore, we investigated the role of glutamate in pregabalin-seeking behavior with ceftriaxone (CEF), a potent GLT-1 upregulator. Mice treated with pregabalin 60 and 90 mg/kg doses demonstrated drug seeking-like behavior, which was significantly blocked by CEF pretreatment. These results suggest that pregabalin-induced CPP was successfully modulated by CEF which could serve as a lead compound for developing treatment for pregabalin abuse.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Althobaiti YS,Almalki A,Alsaab H,Alsanie W,Gaber A,Alhadidi Q,Hardy AMG,Nasr A,Alzahrani O,Stary CM,Shah ZAdoi
10.1038/s41598-019-51556-4subject
Has Abstractpub_date
2019-10-22 00:00:00pages
15136issue
1issn
2045-2322pii
10.1038/s41598-019-51556-4journal_volume
9pub_type
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