Modulation of long-term depression by dopamine in the mesolimbic system

Long-lasting adaptations in the mesolimbic dopamine (DA) system in response to drugs of abuse likely mediate many of the behavioral changes that under lie addiction. Recent work suggests that long-term changes in synaptic stre ngth at excitatory synapses in the two major components of this system, the nucleus accumbens (NAc) and ventral tegmental area, may be particularly im portant for the development of drug-induced sensitization, a process that m ay contribute to addiction, as well as for normal response-reinforcement le arning. Using whole-cell patch-clamp recording techniques from in vitro sli ce preparations, we have examined the existence and basic mechanisms of lon g-term depression (LTD) at excitatory synapses on both GABAergic medium spi ny neurons in the NAc and dopaminergic neurons in the midbrain. We find tha t both sets of synapses express LTD but that their basic triggering mechani sms differ. Furthermore, DA blocks the induction of LTD in the midbrain via activation of D2-like receptors but has minimal effects on LTD in the NAc. The existence of LTD in mesolimbic structures and its modulation by DA rep resent mechanisms that may contribute to the modifications of neural circui try that mediate reward-related learning as well as the development of addi ction.