Repeated administration of citalopram and imipramine alters the responsiveness of rat hippocampal circuitry to the activation of 5-HT7 receptors.
ABSTRACT The effects of a selective serotonin reuptake inhibitor, citalopram, and a tricyclic antidepressant drug, imipramine, administered repetitively for 14 days, were investigated ex vivo in rat hippocampal slices. Spontaneous epileptiform bursts were recorded from the CA3 area in nominally Mg(2+)-free incubation conditions. 5-carboxamidotryptamine (5-CT) dose-dependently increased bursting frequency in the presence of N-[2-[4-(2-methoxyphenyl)-1 piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY 100635). This effect could be dose-dependently blocked by (2R)-1-[(3-Hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine hydrochloride (SB 269970), thus implicating the involvement of 5-HT(7) receptors. Repeated treatment with citalopram or imipramine resulted in an attenuation of the excitatory effects of the activation of hippocampal 5-HT(7) receptor.
Article: Imipramine counteracts corticosterone-induced alterations in the effects of the activation of 5-HT(7) receptors in rat hippocampus.[show abstract] [hide abstract]
ABSTRACT: Using extracellular recording we studied changes in the reactivity of rat hippocampal slices to an agonist of the 5-HT(7) receptor, 5-carboxamidotryptamine (5-CT; 0.025-1 microM), induced by an earlier treatment of animals with corticosterone. Spontaneous bursting activity was recorded in ex vivo slices incubated in the presence of 2-[4-(2-methoxyphenyl)-1piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY 100635; 2 microM), an antagonist of the 5-HT(1A) receptor, in the medium devoid of Mg2+ ions. Saturation binding assays were performed using [(3)H]-(2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine hydrochloride (SB 269970), a specific antagonist of the 5-HT(7) receptor. Repetitive, but not single, corticosterone administration lasting 7 and 21 days, resulted in an enhancement of the effect related to the 5-HT(7) receptor activation without changes in its binding properties. In a separate set of experiments rats were treated with corticosterone for 3 weeks and additionally with imipramine, beginning on the eighth day of corticosterone administration. In the corticosterone plus imipramine group the excitatory effect of 5-CT was weaker than in the corticosterone group, indicating that corticosterone-induced functional modifications in the reactivity of the 5-HT(7) receptor were reversed and further weakened by imipramine treatment. This effect was accompanied by a reduction in the density of [3H]-SB 269970 binding sites. Thus, imipramine treatment counteracts the corticosterone-induced increase in the reactivity of the hippocampal circuitry to the activation of the 5-HT(7) receptor.Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 07/2009; 60(2):83-8. · 2.27 Impact Factor
Article: Influence of serotonin 5-HT(7) receptor blockade on the behavioral and neurochemical effects of imipramine in rats.[show abstract] [hide abstract]
ABSTRACT: The aim of the present study was to examine the effect of the selective 5-HT(7) receptor antagonist (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine (SB-269970), administered alone or in combination with imipramine, on the immobility time of rats in the forced swim test as well as on the extracellular levels of dopamine (DA), noradrenaline (NA), serotonin (5-HT) and their metabolites in the prefrontal cortex of freely moving rats. Both compounds were administered intraperitoneally (ip). Like imipramine (30 mg/kg, but not 20 mg/kg), SB-269970 (1.25 and 2.5 mg/kg, but not 0.625 mg/kg) significantly shortened the immobility time of rats without affecting their exploratory locomotor activity measured in the open field test. SB-269970 (0.625 and 1.25 mg/kg) raised the extracellular levels of DA, NA, 5-HT and their metabolites in rat prefrontal cortex. In that structure, imipramine (20 mg/kg) produced an increase in all the neurotransmitters measured, but failed to affect the levels of their metabolites. A combination of the inactive doses of SB-269970 (0.625 mg/kg) and imipramine (20 mg/kg) found in the forced swim test produced antidepressant-like effect, which did not stem from the increased exploratory locomotor activity. At the same time, that combination voked a vast increase in the output of NA - but not DA and 5-HT - compared to the effects of both those drugs given alone. These results open up a possibility that the stimulating effect of SB-269970 on DA, NA and 5-HT transmission in the prefrontal cortex plays some role in the antidepressant-like activity of this compound. Moreover, these findings suggest that the increase in cortical NA level seems to account for the anti-immobility action observed after joint administration of the selective 5-HT(7) receptor antagonist and imipramine in rats.Pharmacological reports: PR 60(4):464-74. · 2.44 Impact Factor
Article: Effects of repetitive administration of tianeptine, zinc hydroaspartate and electroconvulsive shock on the reactivity of 5-HT(7) receptors in rat hippocampus.[show abstract] [hide abstract]
ABSTRACT: The influence of repeated administration of tianeptine, an atypical antidepressant, which was administered twice daily (10 mg/kg) for 14 days and zinc hydroaspartate, a compound exhibiting antidepressant-like activity, which was administered twice daily (65 mg/kg) for 14 days, and the effects of electroconvulsive shocks (ECS) delivered once daily for 10 days, were investigated ex vivo in rat hippocampal slices. Slices were prepared 2 days after the last session of treatment of animals, and spontaneous epileptiform bursts were recorded extracellularly from the CA3 area. 5-HT(7) receptor-mediated increase in bursting frequency was induced by bath application of of 5-carboxamidotryptamine (5-CT; 0.025-1 microM) in the presence of N-[2-[4-(2-methoxyphenyl)-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY 100635; 2 microM), an antagonist of the 5-HT(1A) receptor. The data indicate an enhancement of the excitatory effect of the activation of 5-HT(7) receptors after ECS repeated ten times, but not by a single ECS. Neither tianeptine nor zinc, administered for 14 days, altered the reactivity of 5-HT(7) receptors.Pharmacological reports: PR 59(6):627-35. · 2.44 Impact Factor