The Roles of Dopamine and α1-Adrenergic Receptors in Cocaine Preferences in Female and Male Rats

Neuropsychopharmacology. 2015 Nov;40(12):2696-704. doi: 10.1038/npp.2015.116. Epub 2015 Apr 22.


Cocaine dependence is characterized by compulsive drug taking and reduced involvement in social, occupational, or recreational activities. Unraveling the diverse mechanisms contributing to the loss-of-interest in these 'non-drug' pursuits is essential for understanding the neurobiology of addiction and could provide additional targets for treating addiction. The study objectives were to examine changes in cocaine-induced dopamine (DA) overflow in the nucleus accumbens (NAc) over the course of self-administration and determine the roles of α1- and β-adrenergic receptors (AR) in the loss-of-interest in food rewards following the development of an addicted phenotype in male and female rats. Subjects were given access to cocaine and palatable food pellets in a choice self-administration paradigm to identify 'addicted' cocaine-preferring (CP) individuals and resistant pellet-preferring (PP) individuals based on their patterns of self-administration over 7 weeks. Cocaine-induced DA overflow in the NAc was examined with microdialysis early and late during self-administration (weeks 2 and 7). Subjects were treated in counter-balanced order with propranolol (β-AR antagonist), terazosin (α1-AR antagonist), or vehicle for an additional 3 weeks of self-administration. CP rats displayed increased motivation for cocaine and attenuated motivation for pellets following the development of cocaine preferences. In females, the estrous cycle affected pellet, but not cocaine, self-administration. CP rats displayed attenuated cocaine-induced DA overflow in the NAc. Propranolol enhanced cocaine reinforcement and reduced pellet intake, whereas terazosin enhanced motivation for pellets and reversed preferences in a subset of CP rats. The implications of these results for the treatment of addiction are discussed.

Publication types

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

MeSH terms

  • Adrenergic Agents / pharmacology
  • Animals
  • Behavior, Addictive / physiopathology
  • Behavior, Addictive / psychology
  • Cocaine / administration & dosage*
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology
  • Dopamine Uptake Inhibitors / administration & dosage*
  • Estrous Cycle / drug effects
  • Female
  • Male
  • Microdialysis
  • Motivation*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, alpha-1 / metabolism*
  • Receptors, Dopamine / metabolism*
  • Reinforcement Schedule
  • Reinforcement, Psychology
  • Self Administration
  • Sex Characteristics*
  • Statistics, Nonparametric


  • Adrenergic Agents
  • Dopamine Uptake Inhibitors
  • Receptors, Adrenergic, alpha-1
  • Receptors, Dopamine
  • Cocaine