Citalopram has an Antagonistic Action on Cortical Spreading Depression in Well-nourished and Early-malnourished Adult Rats

Abstract

Adult, well-nourished (W) and early-malnourished (M) male Wistar rats were injected intraperitoneally for 7 days with 20 mg/kg CIT and cortical spreading depression (CSD) was recorded for 4 h on the day following the treatment. M-animals presented lower body weights, as well as higher CSD velocities of propagation, than the W ones, as previously reported. Compared to saline-injected controls, rats treated with CIT for 7 days presented comparable body weights and lower mean CSD velocities, per hour of recording, the differences being significant at the second hour (3.29+/-0.31 versus 3.56+/-0.40 mm/min; P < 0.05). Topical, cortical application of CIT (1- and 5 mg/ml solutions over the intact dura-mater) reduced dose-dependently the CSD velocity (maximal reductions of 16.3 and 55.8% for the 1 and 5 mg/ml solutions, respectively; P < 0.05), as well as the amplitude of the CSD-slow potential change (58.2 and 88.3%). In three out of seven W-rats and in one out of seven M-rats, topical CIT (5 mg/ml) blocked CSD propagation. The effects were reverted by flushing the treated region with saline. In the M-groups, CIT affected CSD in the same manner as in the W ones. The results reinforce previous evidence for an antagonistic influence of the serotoninergic activity on CSD.

Physical exercise versus fluoxetine: Antagonistic effects on cortical spreading depression in Wistar rats

“…In another study, voluntary wheel running for 4 weeks increased hippocampal levels of serotonin and the mRNA of receptor 5-HT 1A (Wang et al, 2013). Moreover, an antagonistic effect on CSD propagation of increasing brain serotonin availability has been demonstrated ([Amâncio-dos-Santos et al, 2006,Guedes et al, 2002). Thus, this probable role of physical exercise in activating the serotoninergic system could explain its effect on CSD.…”

“…Examples include D-fenfluramine, a serotonin releaser (Cabral-Filho et al, 1995); sumatriptan, a serotonin agonist (Read and Pearsons, 2000); and another SSRI, citalopram (Guedes et al, 2002). In contrast, tianeptine, a serotonin reuptake enhancer, facilitates CSD propagation (Amâncio-dos-Santos et al, 2013).…”

“…A relationship between serotonin and brain excitability has been reported with other SSRIs (Amâncio-dos-Santos et al, 2006;Guedes et al, 2002). Citalopram can reduce the occurrence of spontaneous high-frequency oscillations that occur in epileptic seizures (Pardo-Peña et al, 2014).…”

“…Escitalopram promotes a decreased frequency, duration, and intensity of episodes of migraine (Tarlaci, 2009). Additionally, serotonin exerts an antagonistic effect on cortical spreading depression (CSD) ([Amâncio-dos-Santos et al, 2006,Amâncio-dos-Santos et al, 2013,Guedes et al, 2002, Read and Parsons, 2000). CSD has been described as a slowly propagating wave of depression of spontaneous cortical electrical activity that occurs with chemical, electrical, or mechanical stimulation of one point of cortical tissue (Leão, 1944).…”

Acute tryptophan administration impairs cortical spreading depression propagation in REM sleep deprived and non-deprived adult rats.

“…For example, a single ip injection of the specific serotonin releaser d-fenfluramine, administered during the CSD recording session, antagonizes this phenomenon in the adult rat neocortex (Cabral-Filho et al, 1995). Other serotoninergic drugs, like dihydroergotamine (Barkley et al, 1992), 8-OH-DPAT (Kruger, Heinemann, & Luhmann, 1999, sumatriptan (Read & Parsons, 2000), citalopram (Guedes et al, 2002) and fluoxetine (Amancio-dos- ) also attenuate several CSD features. These data suggest the existence of one or more serotonin-mediated antagonistic processes influencing CSD.…”