Modulation of [3H]paroxetine binding to the 5-hydroxytryptamine uptake site in an animal model of depression.
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.
Edwards
E
E
Department of Psychiatry and Behavioral Science, State University of New York, Stony Brook 11794-8101.
Harkins
K
K
Wright
G
G
Henn
F
F
D000818:Animals; D001665:Binding Sites; D003863:Depression / Q000378:metabolism*; D008297:Male; D017374:Paroxetine; D010880:Piperidines / Q000378:metabolism*; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*; D012016:Reference Values; D012702:Serotonin Antagonists / Q000378:metabolism; D014316:Tritium
D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014316:Tritium; D017374:Paroxetine