Modulation of [3H]Paroxetine Binding to the 5‐Hydroxytryptamine Uptake Site in an Animal Model of Depression

Emmeline Edwards, Kelly Harkins, George Wright, Fritz Henn

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32 Scopus citations


Abstract: The effects of learned helplessness on the 5‐hydroxytryptamine (5‐HT) uptake site were studied in rats using [3H]paroxetine binding. This ligand was chosen because it was demonstrated to label directly the 5‐HT uptake site whereas the [3H]imipramine binding site has been demonstrated to be heterogeneous in nature. Moreover, [3H]imipramine appears to bind to a presynaptic recognition site different from the uptake site. Exposure to uncontrollable shock training and testing resulted in an overall increase in [3H]paroxetine binding in all the groups studied [nonhelpless (NLH), learned helpless (LH), spontaneously helpless (SPLH)] as compared to naive controls (NC). However, the increase in [3H]paroxetine binding was significantly higher in the LH and SPLH groups. The maximum number of [3H]paroxetine binding sites in the rat hippocampus was increased significantly in learned helpless rats (LH and SPLH) at day 4 and day 30 after the shock escape test as compared to NC and NLH rats. By contrast, in the rat hypothalamus the maximum number of [3H]paroxetine binding sites was reduced significantly in the LH rats as compared to naive controls and NLH rats during the same time course. There was no change in [3H]paroxetine binding sites in any other brain regions examined in LH, NLH, and NC rats. The results suggest that a hippocampal hypothalamic connection might play a role in the serotonergic mediation of learned helpless behavior.

Original languageEnglish
Pages (from-to)1581-1586
Number of pages6
JournalJournal of Neurochemistry
Issue number5
StatePublished - May 1991
Externally publishedYes


  • 5‐Hydroxytryptamine
  • 5‐Hydroxytryptamine transporter
  • 5‐Hydroxytryptamine uptake
  • Learned helplessness
  • [H]Paroxetine


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