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 receptor subpopulations in the brain were evaluated pharmacologically, electrophysiologically 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 similar, 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 the density of and increased the affinity for 5-HT1A receptors ([H-3]-8-OH-DPAT used as ligand) in the hippocampus, while imipramine induced opposite 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 antagonized TFMPP-induced hyperthermia (another putative 5-HT2C effect). 5-HTP-induced head twitches (a 5-HT2A effect) were inhibited by repeated paroxetine or imipramine. Either antidepressant given repeatedly decreased 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 changes in 5-HT2 receptors, which lead to reduction of the 5-HT2 neurotransmission (reduced responsiveness of 5-HT2 postsynaptic receptors). The consequences of the secondary changes in 5-HT1A receptors, found here still await clarification.