Regulation of glutamate release onto VTA dopamine neurons via CRF. Top, Under normal conditions, presynaptic CRF-R1 potentiates glutamate release onto AMPA receptors on dopamine neurons. CRF-R2 activation potentiates GABA release, which activates postsynaptic GABA-A receptors and presynaptic GABA-B receptors on glutamatergic terminals. Bottom, After cocaine-self-administration, GABA release is potentiated, suppressing glutamate release. After yohimbine plus cue-induced reinstatement, CRF-R2 activation decreases GABA release via an adenosine receptor-dependent mechanism.