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

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.