[H-3] 8-OH-DPAT BINDING AND SEROTONIN CONTENT IN RAT CEREBRAL-CORTEX AFTER ACUTE FLUOXETINE, DESIPRAMINE, OR PARGYLINE

Cortical serotonin(1A) (5-HT1A) receptors in the rat were studied foll owing acute (24 hours) intraperitoneal administrations of the 5-HT upt ake inhibitor fluoxetine (10 mg/kg), the antidepressant desipramine (2 0 mg/kg), or the monoamine oxidase (MAO) inhibitor pargyline (75 mg/kg ). The 5-HT1A receptors were labelled in total cortex membrane homogen ates with [H-3]8-OH-DPAT, and the monoamines measured in cingulate cor tex by high-performance liquid chromatography. As expected, after parg yline 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 aci d and homovanillic acid. However, neither desipramine nor fluoxetine c hanged monoamine concentrations. Saturation binding with [H-3]8-OH-DPA T 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 c hanges in affinities or binding capacities. In competition experiments with 5-HT, buspirone, and pindolol, the curves were always best fitte d to a 2-site model. Following fluoxetine administration, the inhibiti on curves revealed decreases in the affinity of the low-affinity site (Ki(L)) for the agonist buspirone, and in the relative proportion of t hese sites. In addition, following pargyline, there was an increase in the affinity of the high-affinity site (K-iH) for 5-HT but with a dec rease of the relative proportion of high-affinity sites. The results c onfirm that [H-3]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. Mo reover, the data may reflect an alteration of the coupling efficacy be tween cortical 5-HT1A receptors and their associated G proteins.