Regulation of the ventral tegmental area by the bed nucleus of the stria terminalis is required for expression of cocaine preference

Gregory C. Sartor, Gary Aston-Jones

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Lateral hypothalamus (LH) orexin neurons are essential for the expression of a cocaine place preference. However, the afferents that regulate the activity of these orexin neurons during reward behaviors are not completely understood. Using tract tracing combined with Fos staining, we examined LH afferents for Fos induction during cocaine preference in rats. We found that the ventral bed nucleus of the stria terminalis (vBNST) was a major input to the LH orexin cell field that was significantly Fos-activated during cocaine conditioned place preference (CPP). Inactivation of the vBNST with baclofen plus muscimol blocked expression of cocaine CPP. Surprisingly, such inactivation of the vBNST also increased Fos induction in LH orexin neurons; as activity in these cells is normally associated with increased preference, this result indicates that a vBNST-orexin connection is unlikely to be responsible for CPP that is dependent on vBNST activity. Because previous studies have revealed that vBNST regulates dopamine cells in the ventral tegmental area (VTA), which is known to be involved in CPP and other reward functions, we tested whether vBNST afferents to the VTA are necessary for cocaine CPP. We found that disconnection of the vBNST and VTA (using local microinjections of baclofen plus muscimol unilaterally into the vBNST and contralateral VTA) significantly attenuated expression of cocaine preference. However, blocking ionotropic glutamatergic afferents to the VTA from the vBNST did not significantly reduce cocaine preference. These results indicate that a non-glutamatergic vBNST-VTA projection is involved in expression of cocaine preference. Although several studies have found a strong functional and anatomical projection from ventral bed nucleus of the stria terminalis (vBNST) to neurons in ventral tegmental area (VTA), it was unknown if this circuit is important in reward-related behaviors. Using local inactivations and cocaine conditioned place preference, we show that inhibition of vBNST or its inputs to VTA significantly attenuated cocaine place preference. Thus, these studies shed light on novel connections involved in cocaine reward.

Original languageEnglish (US)
Pages (from-to)3549-3558
Number of pages10
JournalEuropean Journal of Neuroscience
Issue number11
StatePublished - Dec 2012
Externally publishedYes


  • Bed nucleus of the stria terminalis
  • Cocaine
  • Conditioned place preference
  • Lateral hypothalamus
  • Orexin
  • Ventral tegmental area

ASJC Scopus subject areas

  • Neuroscience(all)


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