Potent regulation of midbrain dopamine neurons by the bed nucleus of the stria terminalis

Recent studies have revealed an important role of the ventrolateral (subcom missural) aspect of the bed nucleus of the stria terminalis (vBNST) in moti vational aspects of drug abuse (Delfs et al., 2000). Dopaminergic (DA) neur ons in the ventral tegmental area (VTA) have also long been linked to motiv ation and drug abuse (Koob and Le Moal, 2001). The present study tested whe ther activity in the vBNST influences discharge of midbrain DA neurons. Res ponses of DA neurons in the VTA to activation of the vBNST were characteriz ed in anesthetized rats using extracellular recording techniques. Electrica l or chemical [10-50 mM glutamate (Glu)] stimulation of the vBNST consisten tly activated DA cells (122% increase in activity with 50 mM Glu). However, stronger chemical stimulation of the vBNST (100 mM Glu) completely inactiv ated DA neurons. In addition, apomorphine restored the activity of DA neuro ns that were inactivated by 100 mM Glu stimulation of the vBNST, indicating possible depolarization blockade of DA cells by vBNST activity. These find ings reveal that the vBNST exerts a strong excitatory influence on DA neuro ns. Also striking was the finding that chemical stimulation (50 mM Glu) of the vBNST yielded long-lasting oscillatory activity (>15 min) in VTA DA neu rons. These results indicate that the vBNST can generate long-lasting alter ations in the activity of DA neurons in vivo.