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Targeting the glutamatergic system to treat pathological gambling: current evidence and future perspectives

Mauro Pettorruso, Luisa De Risio, Giovanni Martinotti, Marco Di Nicola, Filippo Ruggeri, Gianluigi Conte, Massimo Di Giannantonio, Luigi Janiri
BioMed Research International 2014, 2014: 109786
25013755
Pathological gambling or gambling disorder has been defined by the DSM-5 as a behavioral addiction. To date, its pathophysiology is not completely understood and there is no FDA-approved treatment for gambling disorders. Glutamate is the principal excitatory neurotransmitter in the nervous system and it has been recently involved in the pathophysiology of addictive behaviors. In this paper, we review the current literature on a class of drugs that act as modulating glutamate system in PG. A total of 19 studies have been included, according to inclusion and exclusion criteria. Clinical trial and case series using glutamatergic drugs (N-acetylcysteine, memantine, amantadine, topiramate, acamprosate, baclofen, gabapentin, pregabalin, and modafinil) will be presented to elucidate the effectiveness on gambling behaviors and on the related clinical dimensions (craving, withdrawal, and cognitive symptoms) in PG patients. The results have been discussed to gain more insight in the pathophysiology and treatment of PG. In conclusion, manipulation of glutamatergic neurotransmission appears to be promising in developing improved therapeutic agents for the treatment of gambling disorders. Further studies are required. Finally, we propose future directions and challenges in this research area.

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