The Neuroscience Of Cocaine: Mechanisms And Treatment

The fundamental role of D-serine as co-agonist 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 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 in 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.