title: Overcoming the effects of stress on synaptic plasticity in the intact hippocampus: rapid actions of serotonergic and antidepressant agents.
abstract: Acute inescapable stress dramatically affects the inducibility of plasticity at glutamatergic synapses in the intact hippocampus. The present study examined the involvement of serotonergic mechanisms in mediating and modulating the block of long-term potentiation (LTP) in the CA1 area of anesthetized rats after exposure to an elevated platform stress. Fluoxetine and fenfluramine, agents that raise hippocampal extracellular 5-HT concentration, blocked the induction of LTP in nonstressed animals, thus mimicking the effect of stress. In contrast, (+/-)-tianeptine, a drug that decreases 5-HT levels, had no effect on LTP induction in nonstressed animals. Remarkably, (+/-) administration of tianeptine after the stress rapidly overcame the block of LTP induction without affecting baseline excitatory transmission. Consistent with a reduction of 5-HT levels being responsible for this effect of tianeptine, the (-) enantiomer, which is associated with the 5-HT uptake enhancing action of (+/-)-tianeptine, also caused a recovery of the induction of LTP in previously stressed animals, whereas the relatively inactive (+) enantiomer had no effect. Furthermore, fluoxetine prevented the effect of tianeptine in stressed animals. These findings show that antidepressants have rapid and powerful interactions with the mechanisms controlling the persistence of the block of LTP by inescapable stress.
authors.affiliation: Department of Pharmacology and Therapeutics, Trinity College, Dublin 2, Ireland.
authors.forename: Alison C
authors.initials: AC
authors.lastname: Shakesby
authors.forename: Roger
authors.initials: R
authors.lastname: Anwyl
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rowan
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D004336:Drug Antagonism; D004567:Electrodes, Implanted; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005080:Exercise Test / Q000187:drug effects; D005277:Fenfluramine / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000502:physiology; D018490:Serotonin Agents / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013312:Stress, Physiological / Q000097:blood; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D013841:Thiazepines / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; D003345:Corticosterone; D005277:Fenfluramine; D005473:Fluoxetine; D012701:Serotonin; D018490:Serotonin Agents; D017367:Selective Serotonin Reuptake Inhibitors; D013841:Thiazepines; C050504:tianeptine