ABSTRACT
Drug addiction is a major public health issue worldwide. The persistence of drug craving coupled with the known recruitment of learning and memory centers in the brain has led investigators to hypothesize that the alterations in glutamatergic synaptic efficacy brought on by synaptic plasticity may play key roles in the addiction process. Here we review the present literature, examining the properties of synaptic plasticity within drug reward circuitry, and the effects that drugs of abuse have on these forms of plasticity. Interestingly, multiple forms of synaptic plasticity can be induced at glutamatergic synapses within the dorsal striatum, its ventral extension the nucleus accumbens, and the ventral tegmental area, and at least some of these forms of plasticity are regulated by behaviorally meaningful administration of cocaine and/or amphetamine. Thus, the present data suggest that regulation of synaptic plasticity in reward circuits is a tractable candidate mechanism underlying aspects of addiction.
Subject(s)
Pharmaceutical Preparations , Synapses/drug effects , Corpus Striatum/drug effects , Corpus Striatum/physiology , Humans , Illicit Drugs/pharmacology , Learning/physiology , Long-Term Potentiation/drug effects , Long-Term Potentiation/physiology , Long-Term Synaptic Depression/drug effects , Neuronal Plasticity , Receptors, Metabotropic Glutamate/physiology , Substance-Related Disorders/physiopathologyABSTRACT
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 Mg(2+) 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.
