Antidepressant-induced adaptive changes in the effects of 5-HT, 5-HT1A and 5-HT4 agonists on the population spike recorded in hippocampal CA1 cells do not involve presynaptic effects on excitatory synaptic transmission.
Effects of repeated treatment with antidepressant drugs on the reactivity of CA1 neurons to 5-hydroxytryptamine (5-HT), (+/-)-8-hydroxy-2-(dipropyl-amino)-tetralin (8-OH-DPAT)--the 5-HT1A receptor agonist, and the zacopride-5-HT4 receptor agonist were examined in the rat hippocampus ex vivo. We sought to assess whether a presynaptic action of 5-HT receptor agonists on excitatory synaptic transmission contributed to the antidepressant-induced adaptive changes in responsiveness of pyramidal neurons to 5-HT1A and 5-HT4 receptor activation. The dendritic population excitatory postsynaptic potential (EPSP) evoked in the stratum radiatum of the CA1 region by stimulation of the Schaffer collateral-commissural pathway, was employed as a measure of the excitatory amino acid-mediated synaptic transmission, while the population spike recorded simultaneously in the CA1 cell layer was a measure of pyramidal cell excitability. 5-HT (10 microM) and 8-OH-DPAT (1 microM) decreased (by 40 +/- 5% and 30 +/- 7%, respectively), while zacopride (20 microM) increased (by 50 +/- 8%) the amplitude of the population spike. Neither drug had any effect on the slope of the population EPSP. The selective 5-HT1B receptor agonist CGS-12066 had no effect on the population spike or on the EPSP. Repeated treatment (14 days, twice daily, 10 mg/kg po) with imipramine and paroxetine augmented the inhibitory action of 5-HT on the population spike (by 50%), whereas treatment with citalopram and fluvoxamine had no effect. Imipramine and paroxetine, but not fluvoxamine, increased the 8-OH-DPAT-induced inhibition (by 80-100%). All of the antidepressant drugs studied attenuated the excitatory effect of zacopride on the population spike (by 70%). The population EPSPs in slices from rats treated with antidepressant drugs were not affected by 5-HT, 8-OH-DPAT or zacopride. It has been concluded that adaptive changes in the responsiveness of CA1 cells to 5-HT, 8-OH-DPAT and zacopride, induced by repeated administration of antidepressant drugs do not involve presynaptic effects on excitatory synaptic transmission.
Tokarski
K
K
Department of Neurobiology, Polish Academy of Sciences, Kraków, Poland.
Bijak
M
M
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D015283:Citalopram / Q000494:pharmacology; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D016666:Fluvoxamine / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D017374:Paroxetine / Q000494:pharmacology; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D009435:Synaptic Transmission / Q000187:drug effects*
D000928:Antidepressive Agents; D001549:Benzamides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011810:Quinoxalines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D015283:Citalopram; C052561:CGS 12066B; D012701:Serotonin; D017374:Paroxetine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C055971:zacopride; D016666:Fluvoxamine; D007099:Imipramine