Two determinants of dopamine release from terminals in striatal and limbic structures are the pattern and rate of dopamine neuron firing in the ventral midbrain. This activity is regulated in part by somatodendritic release of dopamine and subsequent feedback inhibition through activation of D2receptors on dopamine neuron cell bodies and dendrites. This study describes stimulus-dependent long-term depression (LTD) of IPSCs mediated by dopamine. This LTD was blocked by chelation of postsynaptic intracellular calcium, was dependent on the activation of D2receptors and was independent of glutamate-mediated transmission. Application of a high concentration of dopamine mimicked depression of the IPSC and prevented additional attempts to induce LTD, suggesting that the mechanism of the depression is agonist-dependent receptor activation. Using extracellular recording, there is an inhibition of firing that follows electrical stimulation, and after the induction of LTD the duration of that inhibition was decreased. Reduced inhibition could increase burst firing and action potential-dependent release of dopamine in terminal regionsin vivo.