Profound changes in glutamate neurotransmission within the nucleus accumbens are linked to the behavioral sensitization and addiction caused by cocaine. Remodeling of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor (AMPAR) via differential pairing of the four GluR subunits is observed during withdrawal after chronic cocaine administration, and it has been hypothesized that the neuronal pentraxin proteins could affect cocaine-induced synaptic changes via regulation of AMPAR clustering and uptake. The neuronal pentraxin 1 (NP1) and neuronal activity-regulated pentraxin (Narp) oligomerize with AMPAR to enhance synaptic signaling, whereas the neuronal pentraxin receptor (NRP) induces AMPAR uptake. In this issue, the study reported by Pacchioni et al., shows that deletion of either Narp or NP1 produced similar effects on cocaine-induced behavior as well as reduced AMPA responsiveness and GluR1 expression after withdrawal. In contrast, deletion of NPR potentiated the AMPA response after withdrawal. These results suggest that the pentraxin system partly regulates the synaptic plasticity during cocaine addiction.
See article at J Pharmacol Exp Ther 2009, 328:183–192.
- The American Society for Pharmacology and Experimental Therapeutics