[3H]8-OH-DPAT binding and serotonin content in rat cerebral cortex after acute fluoxetine, desipramine, or pargyline.
Cortical serotonin1A (5-HT1A) receptors in the rat were studied following acute (24 hours) intraperitoneal administrations of the 5-HT uptake inhibitor fluoxetine (10 mg/kg), the antidepressant desipramine (20 mg/kg), or the monoamine oxidase (MAO) inhibitor pargyline (75 mg/kg). The 5-HT1A receptors were labelled in total cortex membrane homogenates with [3H]8-OH-DPAT, and the monoamines measured in cingulate cortex by high-performance liquid chromatography. As expected, after pargyline administration tissue concentrations of 5-HT, noradrenaline (NA) and dopamine (DA) were markedly increased due to MAO inhibition with a concomitant decrease of the metabolites 5-hydroxyindole-3-acetic acid and homovanillic acid. However, neither desipramine nor fluoxetine changed monoamine concentrations. Saturation binding with [3H]8-OH-DPAT revealed that, for the control animals (saline treated), the curves were best fitted to a 2-site model. Following drug administration, the saturation curves were still best fitted to a 2-site model, with no changes in affinities or bonding capacities. In competition experiments with 5-HT, buspirone, and pindolol, the curves were always best fitted to a 2-site model. Following fluoxetine administration, the inhibition curves revealed decreases in the affinity of the low-affinity site (KiL) for the agonist buspirone, and in the relative proportion of these sites. In addition, following pargyline, there was an increase in the affinity of the high-affinity site (KiH) for 5-HT but with a decrease of the relative proportion of high-affinity sites. The results confirm that [3H]8-OH-DPAT binding is to a 2-site model, and reveal an absence of downregulation of 5-HT1A receptors following increases in tissue 5-HT after MAO inhibition or antidepressant administrations. Moreover, the data may reflect an alteration of the coupling efficacy between cortical 5-HT1A receptors and their associated G proteins.
Carli
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Centre de recherche en sciences neurologiques, Département de physiologie, Universite de Montreal, Quebec, Canada.
Afkhami-Dastjerdian
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Reader
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001665:Binding Sites; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D005473:Fluoxetine / Q000494:pharmacology*; D006179:Gyrus Cinguli / Q000187:drug effects; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D010293:Pargyline / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000378:metabolism*
D000928:Antidepressive Agents; D017366:Serotonin Receptor Agonists; D005473:Fluoxetine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010293:Pargyline; D008995:Monoamine Oxidase; D003891:Desipramine; D004298:Dopamine; D006719:Homovanillic Acid