The dorsal striatum (caudate putamen) contains two types of GABAergic medium spiny neurons (MSNs) that are distinguished by the expression of either the opioid peptide, enkephalin, or the opioid peptide, dynorphin, as well as the tachykinin substance P. Pharmacological studies suggest that these peptides modulate local neurotransmission in the striatum in response to direct and indirect dopamine agonists. In contrast, GABA appears to have minimal impact within the striatum under these conditions. The actions of the peptide cocktail are dependent on the cellular distribution of their receptors in the striatal network. The net result of their actions is a homeostatic response that regulates striatal output and balances dopamine and glutamate receptor stimulation.