THE EFFECTS OF PAROXETINE GIVEN REPEATEDLY ON THE 5-HT RECEPTOR SUBPOPULATIONS IN THE RAT-BRAIN

Effects of paroxetine (10 mg/kg PO, twice daily, 14 days) on 5-HT rece ptor subpopulations in the brain were evaluated pharmacologically, ele ctrophysiologically and biochemically in male Wistar rats. Imipramine was used for comparison. Repeated paroxetine antagonized the 8-OH-DPAT -induced behavioural syndrome (a 5-HT1A effect); imipramine showed sim ilar, yet weaker, activity. The 5-HT- or 8-OH-DPAT-induced inhibition of population spikes in hippocampal slices was increased by both those repeated antidepressants. Repeated (or acute) paroxetine decreased th e density of and increased the affinity for 5-HT1A receptors ([H-3]-8- OH-DPAT used as ligand) in the hippocampus, while imipramine induced o pposite effects. m-Chlorophenyl piperazine (m-CPP)-evoked exploratory hypoactivity, a 5-HT2C effect, was reduced by repeated paroxetine, but not by imipramine. Either of the antidepressants given repeatedly ant agonized TFMPP-induced hyperthermia (another putative 5-HT2C effect). 5-HTP-induced head twitches (a 5-HT2A effect) were inhibited by repeat ed paroxetine or imipramine. Either antidepressant given repeatedly de creased the density of 5-HT2A receptors ([H-3]- ketanserin as a ligand ) in the brain cortex, but did not change their affinity. The present results indicate that paroxetine given repeatedly induces secondary ch anges in 5-HT2 receptors, which lead to reduction of the 5-HT2 neurotr ansmission (reduced responsiveness of 5-HT2 postsynaptic receptors). T he consequences of the secondary changes in 5-HT1A receptors, found he re still await clarification.