| Abstract No.: | B-C2096 |
| Country: | Canada |
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| Title: | CHRONIC FLUOXETINE TREATMENT HAS SIGNIFICANT EFFECT ON THE DENSITY OF 5-HT1A RECEPTORS IN
FLINDERS SENSITIVE LINE RATS BUT NOT IN FLINDERS RESISTANT LINE RATS
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| Authors/Affiliations: | 1 Tomislav Kovacevic *; 1 Ivan Skelin; 2 Hank F. Kung; 1 Mirko Diksic;
1 Montreal Neurological Institute, McGill University,QC, Canada and J. J. Strossmayer University, Faculty of Medicine Osijek, Croatia; 2 University of Pennsylvania, Department of Radiology; Philadelphia, USA;
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| Content: | FSL (Flinders Sensitive Line) and FRL (Flinders Resistant Line) rats were bread from Sprague Dawley (SDR) rats to produce rats increased (FSL) and decreased (FRL) sensitive to a cholinergic drug, diisopropylfluorophosphatet, an inhibitor of cholinesterase. FSL have reduced appetite and psychomotor function, sleep and immune abnormalities, while FRL rats are in many behavioural aspects similar to the SDR and are usually used as control animals for studies of FSL rats. The objective of the present investigation was to assess the changes in 5-HT1A receptor density in rat depression model (FSL rats) relative to those in the FRL rats after chronic fluoxetine treatment.
Rats received fluoxetine or saline, every day for 14 days (10 mg/kg, i. p.). On the 15th day rats were decapitated, brains extracted, frozen in isopantane, and stored at -85°C. The rat brains were cut into 20 µm thick coronal sections in a cryostat. Slides were immersed in the pre-incubation buffer (200 ml, 50 mM Tris-HCl, pH 7.4, containing 2 mM MgCl2)and then in mailers containing 125-I-MPPI (specific activity of 2000 Ci/mmol) in a buffer for 120 min (22.7 µCi in 200 ml). Non-specific binding was measured in the presence of a 10 mM non-radioactive 5-HT.
The sections, along with I-125 standards were exposed to the Fuji fluorescence plates for several hours and calibrated as nCi/mg-tissue. The plates were scanned and images were quantified by a calibration curve obtained from standards in a MCID imaging system, the binding was quantified in more than twenty brain regions. Regional readings were transformed to bindings (fmol/mg) to asses possible influence of fluoxetine treatment on the 5-HT1A receptor densities in FSL and FRL groups. Fluoxetine treated rats were compared to saline treated rats. MANOVA gave highly significant brain region*group interaction; F(25,200)=5.03; p<0.001. Post-hoc ANOVA revealed significant differences in Scx, SMcx, VTA, SNc, MG and DR when comparing FSL and FRL ratio (treatment: saline), with significant elevation in the density of 5-HT1A receptors in all of these regions except DR where there was a significant reduction in the density. of 5-HT1A receptors. The largest increase in the number of 5-HT1A receptors was found in VTA where the density was 2.3 times greater after fluoxetine treatment. The was no significant influence of fluoxetine treatment on the group*region interaction when fluoxetine and saline treatments were compared in FRL rats; F(25,250)=1.16; p>0.2.
The largest differences between effects in the FSL and FRL rats were observed in the VTA, DR, Encx and Amy, suggesting effects of fluoxetine to be especially important in the "depressed" rats in some of the brain limbic regions.
Key words: 5-HT1A receptor, FSL rats, FRL rats, fluoxetine, autoradiography
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