5-HT(1B) receptors in nucleus accumbens efferents enhance both rewarding and aversive effects of cocaine

Eur J Neurosci. 2007 May;25(10):3125-31. doi: 10.1111/j.1460-9568.2007.05568.x. Epub 2007 May 17.


Whether serotonin-1B (5-HT(1B)) receptor activation enhances or diminishes the reinforcing properties of psychostimulants remains unclear. We have previously shown that increased expression of 5-HT(1B) receptors in nucleus accumbens (NAcc) shell neurons sensitized rats to the locomotor-stimulating and rewarding properties of cocaine. In this study we further examined the contribution of 5-HT(1B) receptors on the effect of cocaine under conditions intended to selectively influence either conditioned place preference or avoidance (CPP or CPA, respectively). Viral-mediated gene transfer techniques were used to overexpress 5-HT(1B) receptors in medial NAcc shell medium spiny neurons projecting to the ventral tegmental area. Animals were then conditioned to associate place cues with the effects of either a low (5 mg/kg) or moderately high (20 mg/kg) dosage of cocaine immediately or 45 min after intraperitoneal cocaine administration. Animals with increased 5-HT(1B) expression showed cocaine-induced CPP immediately after administration of the low 5 mg/kg dose of cocaine, but a CPA 45 min after administration of the high 20 mg/kg dose. Control animals showed no preference at the 5 mg/kg dose and a significant preference at 20 mg/kg. Given this, we believe that increased 5-HT(1B) receptor activation in NAcc shell projection neurons intensifies both the rewarding and negative properties of cocaine use.

Publication types

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

MeSH terms

  • Animals
  • Avoidance Learning / drug effects
  • Avoidance Learning / physiology
  • Cocaine / adverse effects*
  • Cocaine-Related Disorders / metabolism*
  • Cocaine-Related Disorders / physiopathology
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology
  • Dopamine Uptake Inhibitors / adverse effects
  • Dose-Response Relationship, Drug
  • Genetic Vectors
  • Injections, Intraperitoneal
  • Male
  • Neurons / drug effects
  • Neurons / metabolism
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism*
  • Nucleus Accumbens / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT1B / drug effects
  • Receptor, Serotonin, 5-HT1B / genetics
  • Receptor, Serotonin, 5-HT1B / metabolism*
  • Reward*
  • Serotonin / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Transfection


  • Dopamine Uptake Inhibitors
  • Receptor, Serotonin, 5-HT1B
  • Serotonin
  • Cocaine