Dopamine depletion abolishes apomorphine- and amphetamine-induced increases in extracellular serotonin levels in the striatum of conscious rats: a microdialysis study

Neuroscience. 2003;119(4):1045-53. doi: 10.1016/s0306-4522(03)00219-7.


We investigated how serotonergic neurotransmission was affected by 6-hydroxydopamine (6-OHDA) lesioning of the adult rat brain dopamine (DA) system. In this animal model for Parkinson's disease (PD), the effect of destroying ascending DA pathways on extracellular levels of serotonin (5-HT) and 5-HT innervation in rat striatum were examined. Profound unilateral lesions of the nigrostriatal DA pathways were made by infusing 6-OHDA unilaterally into either the right medial forebrain bundle or the right substantia nigra. At 5 weeks after lesioning extracellular levels of DA and 5-HT were determined with microdialysis and high-pressure liquid chromatography under basal conditions and after systemic injections of apomorphine or amphetamine. DA nerve-terminal destruction and 5-HT innervation were determined with quantitative autoradiography. 6-OHDA lesioning reduced extracellular levels of DA below detection limits and led to statistically significant increases in extracellular 5-HT. Apomorphine, and amphetamine, respectively increased extracellular 5-HT to 8.2- and 2.2-fold above baseline levels in intact animals; these effects were absent in 6-OHDA-lesioned animals. Basal levels of [(3)H]paroxetine binding to 5-HT transporters in caudate-putamen increased by 41% in 6-OHDA-lesioned animals. These results suggest that 6-OHDA lesioning led to hyperinnervation of 5-HT nerve terminals and increases in basal extracellular 5-HT levels, but also to an unexplained loss of apomorphine and amphetamine-induced release of 5-HT. Addressing whether this impairment has significance in the onset of PD might lead to development of new strategies to manage parkinsonian symptoms.

Publication types

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

MeSH terms

  • Afferent Pathways / drug effects
  • Afferent Pathways / metabolism*
  • Afferent Pathways / physiopathology
  • Amphetamine / pharmacology
  • Animals
  • Apomorphine / pharmacology
  • Binding, Competitive / drug effects
  • Binding, Competitive / physiology
  • Carrier Proteins / drug effects
  • Carrier Proteins / metabolism
  • Denervation
  • Disease Models, Animal
  • Dopamine / deficiency*
  • Dopamine Agonists / pharmacology
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Membrane Glycoproteins / drug effects
  • Membrane Glycoproteins / metabolism
  • Membrane Transport Proteins*
  • Microdialysis
  • Neostriatum / drug effects
  • Neostriatum / metabolism*
  • Neostriatum / physiopathology
  • Nerve Tissue Proteins*
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Oxidopamine
  • Parkinsonian Disorders / drug therapy
  • Parkinsonian Disorders / metabolism*
  • Parkinsonian Disorders / physiopathology
  • Paroxetine / pharmacology
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism*
  • Presynaptic Terminals / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism*
  • Serotonin Plasma Membrane Transport Proteins
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology


  • Carrier Proteins
  • Dopamine Agonists
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Serotonin Plasma Membrane Transport Proteins
  • Slc6a4 protein, rat
  • Serotonin
  • Paroxetine
  • Oxidopamine
  • Amphetamine
  • Apomorphine
  • Dopamine