Dissociating effects of cocaine and d-amphetamine on dopamine and serotonin in the perirhinal, entorhinal, and prefrontal cortex of freely moving rats

Psychopharmacology (Berl). 2007 Aug;193(3):375-90. doi: 10.1007/s00213-007-0791-2. Epub 2007 Apr 29.


Rationale: Neuroimaging studies with humans showed widespread activation of the cortex in response to psychostimulant drugs. However, the neurochemical nature of these brain activities is not characterized.

Objective: The aim of the present study was to investigate the effects of cocaine and d-amphetamine on dopamine (DA) and serotonin (5-HT) in cortical areas of the hippocampal network in comparison to the prefrontal cortex (PFC).

Materials and methods: We conducted in vivo microdialysis experiments in behaving rats measuring DA and 5-HT in the perirhinal cortex (PRC), entorhinal cortex (EC), and PFC, after application of cocaine (0, 5, 10, 20 mg/kg; i.p.) or d-amphetamine (0, 0.5, 1.0, 2.5 mg/kg; i.p.).

Results: Cocaine and d-amphetamine dose-dependently increased DA and 5-HT levels in the PRC, EC, and PFC. A predominant DA response to d-amphetamine was only found in the PFC, but not in the PRC and EC. Cocaine increased DA and 5-HT to an equal extent in the PFC and PRC but induced a predominant 5-HT response in the EC. When comparing the neurochemical responses between the drugs at an equal level of behavioral activation, cocaine was more potent than d-amphetamine in increasing 5-HT in the PFC, while no differences were found in the PRC or EC or in the DA responses in all three cortical areas.

Conclusions: We conclude that cocaine and d-amphetamine increase DA and 5-HT levels in PRC and EC largely to the same extent as in the PFC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amphetamine / administration & dosage
  • Amphetamine / pharmacology*
  • Animals
  • Behavior, Animal / drug effects*
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism
  • Cocaine / administration & dosage
  • Cocaine / pharmacology*
  • Dopamine / metabolism*
  • Dopamine Agents / administration & dosage
  • Dopamine Agents / pharmacology*
  • Dopamine Uptake Inhibitors / administration & dosage
  • Dopamine Uptake Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Locomotion / drug effects
  • Male
  • Microdialysis
  • Rats
  • Rats, Wistar
  • Serotonin / metabolism*


  • Dopamine Agents
  • Dopamine Uptake Inhibitors
  • Serotonin
  • Amphetamine
  • Cocaine
  • Dopamine