Designer receptors show role for ventral pallidum input to ventral tegmental area in cocaine seeking

Nat Neurosci. 2014 Apr;17(4):577-85. doi: 10.1038/nn.3664. Epub 2014 Mar 2.


The ventral pallidum is centrally positioned within mesocorticolimbic reward circuits, and its dense projection to the ventral tegmental area (VTA) regulates neuronal activity there. However, the ventral pallidum is a heterogeneous structure, and how this complexity affects its role within wider reward circuits is unclear. We found that projections to VTA from the rostral ventral pallidum (RVP), but not the caudal ventral pallidum (CVP), were robustly Fos activated during cue-induced reinstatement of cocaine seeking--a rat model of relapse in addiction. Moreover, designer receptor-mediated transient inactivation of RVP neurons, their terminals in VTA or functional connectivity between RVP and VTA dopamine neurons blocked the ability of drug-associated cues (but not a cocaine prime) to reinstate cocaine seeking. In contrast, CVP neuronal inhibition blocked cocaine-primed, but not cue-induced, reinstatement. This double dissociation in ventral pallidum subregional roles in drug seeking is likely to be important for understanding the mesocorticolimbic circuits underlying reward seeking and addiction.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Basal Ganglia / drug effects
  • Basal Ganglia / metabolism*
  • Basal Ganglia / pathology
  • Behavior, Animal / drug effects
  • Cocaine / administration & dosage
  • Cocaine / pharmacology*
  • Cocaine-Related Disorders / metabolism*
  • Cues
  • Disease Models, Animal
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism*
  • Dopaminergic Neurons / physiology
  • Male
  • Neural Inhibition / drug effects
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism*
  • Rats
  • Rats, Long-Evans
  • Rats, Sprague-Dawley
  • Receptors, Dopamine / drug effects
  • Receptors, Dopamine / metabolism*
  • Recurrence
  • Reward
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / metabolism*
  • Ventral Tegmental Area / pathology


  • Receptors, Dopamine
  • Cocaine