D1 dopamine receptor-mediated LTP at GABA synapses encodes motivation to self-administer cocaine in rats

J Neurosci. 2013 Jul 17;33(29):11960-71. doi: 10.1523/JNEUROSCI.1784-13.2013.


Enhanced motivation to take drugs is a central characteristic of addiction, yet the neural underpinning of this maladaptive behavior is still largely unknown. Here, we report a D1-like dopamine receptor (DRD1)-mediated long-term potentiation of GABAA-IPSCs (D1-LTPGABA) in the oval bed nucleus of the stria terminalis that was positively correlated with motivation to self-administer cocaine in rats. Likewise, in vivo intra-oval bed nucleus of the stria terminalis DRD1 pharmacological blockade reduced lever pressing for cocaine more effectively in rats showing enhanced motivation toward cocaine. D1-LTPGABA resulted from enhanced function and expression of G-protein-independent DRD1 coupled to c-Src tyrosine kinases and required local release of neurotensin. There was no D1-LTPGABA in rats that self-administered sucrose, in those with limited cocaine self-administration experience, or in those that received cocaine passively (yoked). Therefore, our study reveals a novel neurophysiological mechanism contributing to individual motivation to self-administer cocaine, a critical psychobiological element of compulsive drug use and addiction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cocaine / administration & dosage*
  • Dopamine / metabolism
  • Dopamine Uptake Inhibitors / administration & dosage*
  • Inhibitory Postsynaptic Potentials / drug effects
  • Inhibitory Postsynaptic Potentials / physiology
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Male
  • Motivation / drug effects
  • Motivation / physiology*
  • Neurotensin / metabolism
  • Rats
  • Rats, Long-Evans
  • Receptors, Dopamine D1 / metabolism*
  • Reinforcement, Psychology
  • Self Administration
  • Septal Nuclei / drug effects
  • Septal Nuclei / physiology
  • Synapses / drug effects
  • Synapses / physiology*
  • gamma-Aminobutyric Acid / metabolism*


  • Dopamine Uptake Inhibitors
  • Receptors, Dopamine D1
  • Neurotensin
  • gamma-Aminobutyric Acid
  • Cocaine
  • Dopamine