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Fluoxetine May Influence Lordosis of Rats through Effects on Midbrain 3α,5α‐THP Concentrations
Author(s) -
FRYE CHERYL A.,
PETRALIA SANDRA M.,
RHODES MADELINE E.,
STEIN BENJAMIN
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1286.004
Subject(s) - ventral tegmental area , midbrain , fluoxetine , endocrinology , lordosis , ovariectomized rat , medicine , chemistry , lordosis behavior , estradiol benzoate , anesthesia , pharmacology , central nervous system , dopamine , serotonin , estrogen , receptor , surgery , radiography , dopaminergic
A bstract : 5α‐pregnan‐3α‐ol‐20‐one (3α,5α‐THP) in the ventral tegmental area (VTA) mediates lordosis of rodents. If fluoxetine's effects on lordosis are mediated in part by midbrain 3α,5α‐THP, then fluoxetine regimens that decrease and increase lordosis would be expected to respectively lower and elevate midbrain 3α,5‐THP levels. Experiment 1: Ovariectomized (ovx) rats received estradiol benzoate (EB; 5 μg, SC) at 0 and 24 h and fluoxetine (20 mg/kg, IP) or vehicle 30 min before sex testing and tissue collection. Other rats received fluoxetine (10 mg/kg, IP) or vehicle for 15 days followed by EB‐priming and testing. Systemic acute or chronic fluoxetine significantly decreased lordosis and midbrain 3α,5α‐THP levels compared to vehicle. Experiment 2: Ovx rats with unilateral cannula to the VTA were primed with EB (5 μg; 0, 24 h) and/or progesterone (0 or 100 μg; 44 h, SC). At 47.5 h, fluoxetine (3.6 mM) or vehicle was infused to the VTA. At 48 h, rats were tested. Administering fluoxetine to the VTA significantly increased lordosis and midbrain 3α,5α‐THP levels compared to vehicle infusions. Experiment 3: Ovx EB‐primed rats were tested prior to, and 30 min after, treatmemt with acute fluoxetine (20 mg/kg, IP). Rats were then infused with 3α,5α‐THP (100 ng) or vehicle to the VTA and were retested. 3α,5α‐THP, but not vehicle, to the VTA reversed acute fluoxetine's inhibitory effects on lordosis. Together, these data suggest fluoxetine may alter lordosis in part through actions of 3α‐THP in the midbrain.