Nigrostriatal dopamine (DA) is critical to action selection and learning. Axonal DA release is locally influenced by striatal neurotransmitters. Striatal neurons are comprised principally of GABAergic neurons, projection neurons and interneurons, while a minority are cholinergic interneurons (ChIs). ChIs strongly gate striatal DA release via identified nicotinic receptors (nAChRs) on DA axons. Striatal GABA is thought to modulate DA, but GABA receptors have not been documented conclusively on DA axons. However, ChIs express GABA receptors, and are therefore key candidates for potential mediators of GABA regulation of DA. We addressed whether striatal GABA and its receptors can modulate DA release directly, independently from ChI regulation, by detecting DA in striatal slices from male mice using fast-scan cyclic voltammetry in the absence of nAChR activation.DA release evoked by single electrical pulses in the presence of nAChR antagonist dihydro-β-erythroidine DHβE, was reduced by GABA or agonists at GABAA or GABAB receptors, with effects prevented by selective GABA receptor antagonists. GABA agonists slightly modified the frequency sensitivity of DA release during short stimulus trains. GABA agonists also suppressed DA release evoked by optogenetic stimulation of DA axons. Furthermore, GABA receptor antagonists significantly enhanced DA release, evoked by either optogenetic or electrical stimuli. These results indicate that striatal GABA can inhibit DA release through GABAA and GABAB receptors, and that these actions are not mediated by cholinergic circuits. Furthermore, these data reveal that there is a tonic inhibition of DA release by GABA, operating through predominantly GABAB receptors.SIGNIFICANCE STATEMENTThe principal inhibitory transmitter in the mammalian striatum, GABA, is thought to modulate striatal dopamine (DA) release, but definitive evidence for GABA receptors on DA axons is lacking. Striatal cholinergic interneurons regulate DA release via axonal nicotinic receptors (nAChRs) and also express GABA receptors, but they have not been eliminated as potentially critical mediators of DA regulation by GABA. Here, we find that GABAA and GABAB receptors inhibit DA release without requiring cholinergic interneurons. Furthermore, ambient levels of GABA inhibited DA release, predominantly through GABAB receptors. These findings provide further support for direct inhibition of DA release by GABA receptors, and furthermore, reveal that striatal GABA operates a tonic inhibition on DA output that could critically influence striatal output.