title: 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.
abstract: 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.
authors.affiliation: Department of Neurobiology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Tokarski
authors.forename: M
authors.initials: M
authors.lastname: Bijak
mesh_terms: 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*
chemical_list: 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