Glutamatergic transmission in the nucleus accumbens (NAc) has been shown to be important for behavioral adaptations in response to drugs of abuse. NMDA-receptor dependent long-term potentiation (LTP) of glutamatergic synaptic transmission has been hypothesized to underlie many lasting alterations in behavior. Thus, we examined LTP in NAc core and find that it is developmentally regulated. Specifically, tetanus-evoked, NMDA receptor-dependent LTP is observed in the NAc of “adolescent” (3-week-old) mice more frequently than in adult (6–20-week-old) mice. In contrast, cAMP-dependent enhancement of transmission is not developmentally regulated. Removal of extracellular Mg2+ restores LTP in adult NAc core, suggesting developmental regulation of induction processes rather than maintenance mechanisms. These findings are discussed in the context of behavioral changes elicited in response to drugs of abuse, which differ in adolescent vs. adult rodents and humans. Synapse 45:213–219, 2002. © 2002 Wiley-Liss, Inc.