Alpha 1-noradrenergic system role in increased motivation for cocaine intake in rats with prolonged access

Eur Neuropsychopharmacol. 2008 Apr;18(4):303-11. doi: 10.1016/j.euroneuro.2007.08.003. Epub 2007 Oct 24.


In rodents, extended access to cocaine produces an escalation in cocaine self-administration that has face and construct validity for human compulsive drug intake. Here we report that rats with six-hour access (long access, LgA) to cocaine self-administration produced a higher breakpoint for cocaine using a progressive-ratio schedule than rats with one-hour access (short access, ShA), and prazosin (alpha 1 receptor antagonist) reduced the higher breakpoint for cocaine in LgA rats. Additionally, the number of neurons with alpha 1-adrenergic receptor-like immunoreactivity in the bed nucleus of stria terminalis (BNST) was found to be much lower in LgA rats than in ShA and drug-naive rats. In contrast, UK14304 (alpha 2 receptor agonist) and betaxolol (beta 1 receptor antagonist) had no effect on cocaine self-administration in either group. The data suggest that activation of the alpha 1-noradrenergic system, perhaps in the BNST, is associated with increased motivation for cocaine in rats with extended access.

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic alpha-Antagonists / pharmacology
  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Betaxolol / pharmacology
  • Brain Chemistry / drug effects
  • Brimonidine Tartrate
  • Cocaine-Related Disorders / metabolism
  • Cocaine-Related Disorders / physiopathology*
  • Cocaine-Related Disorders / psychology*
  • Conditioning, Operant / drug effects
  • Data Interpretation, Statistical
  • Dose-Response Relationship, Drug
  • Immunohistochemistry
  • Male
  • Motivation*
  • Prazosin / pharmacology
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, alpha-1 / metabolism
  • Receptors, Adrenergic, alpha-1 / physiology*
  • Self Administration
  • Septal Nuclei / metabolism


  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Adrenergic beta-Antagonists
  • Quinoxalines
  • Receptors, Adrenergic, alpha-1
  • Brimonidine Tartrate
  • Betaxolol
  • Prazosin