Critical Role of d-Serine Signaling in Synaptic Plasticity Relevant to Cocaine Addiction

The fundamental role of d-serine as coagonist at the n-methyl-. d-aspartate receptor (NMDAR), a major glutamate receptor subtype involved in synaptic plasticity, is well documented and experimental evidence indicates now that this d-amino acid is an influential player in the context of psychiatric diseases such as schizophrenia and depression. More recently, a direct link between cocaine addiction, another neuropsychiatric disorder, and d-serine signaling has been proposed by findings that d-serine levels are decreased in the nucleus accumbens of cocaine-treated rats. Such a deficit in d-serine content leads to impairment of NMDAR-dependent synaptic plasticity and locomotor sensitization to cocaine, a behavioral hallmark of cocaine addiction. The d-serine hypothesis for cocaine addiction, here proposed, provides considerable insight into the understanding of the cocaine-induced neuroadaptations in reward-related neuronal circuits and opens new attractive perspectives for therapeutic approaches to treat this addictive state.