title: Endogenous serotonin facilitates hippocampal long-term potentiation at CA3/CA1 synapses.
abstract: Encoding of episodic memory requires long-term potentiation (LTP) of neurotransmission at excitatory synapses of the hippocampal circuitry. Previous data obtained with the application of exogenous 5-hydroxytryptamine (5-HT) in hippocampal slices indicate that 5-HT blocks LTP, which contrasts with the facilitatory effect of selective serotonin reuptake inhibitors (SSRIs) on learning and memory observed in vivo. Here, we investigated the effects of endogenous 5-HT, released from terminals by the monoamine releaser 3,4-methylenedioxymethamphetamine (MDMA), on LTP of field EPSPs induced by theta-burst stimulation and recorded at CA3/CA1 synapses of rat hippocampal slices. LTP was greater in the presence of MDMA (10 µM; 45.76 ± 15.75%; n = 28) than in controls (31.26 ± 11.03; n = 21; p < 0.01). This facilitatory effect on LTP persisted when the entry of MDMA in noradrenergic terminals was prevented by the selective noradrenaline reuptake inhibitor nisoxetine (44.90 ± 14.07%; n = 27 vs. 34.49 ± 12.94%; n = 20 in controls; p < 0.05). In both conditions, the facilitation of LTP was abolished by the SSRI citalopram that prevented the entry of MDMA in 5-HT terminals and the subsequent 5-HT release. These data show that, unlike exogenous 5-HT application, release of endogenous 5-HT does not impair cellular mechanisms responsible for induction of LTP, indicating that 5-HT is not detrimental to learning and memory. Moreover, facilitation of LTP by endogenous 5-HT may underlie the in vivo positive effects of augmented 5-HT tone on cognitive performance.
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Viale G. Pieraccini 6, 50139, Florence, Italy.
authors.forename: Boris
authors.initials: B
authors.lastname: Mlinar
authors.forename: Gabriella
authors.initials: G
authors.lastname: Stocca
authors.forename: Renato
authors.initials: R
authors.lastname: Corradetti
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics; D056547:CA1 Region, Hippocampal / Q000166:cytology*; D056654:CA3 Region, Hippocampal / Q000166:cytology*; D004558:Electric Stimulation; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
chemical_list: D018490:Serotonin Agents; D005473:Fluoxetine; C011386:nisoxetine; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine