Nutritional status during development can modify the brain's electrophysiological properties and its response to drugs that reduce the serotonin availability in the synaptic cleft. Here we used cortical spreading depression (CSD) in the rat as a neurophysiological parameter to investigate the interaction between nutritional status and treatment with tianeptine, a serotonin uptake enhancer. From postnatal day 2 to 24, well-nourished and early-malnourished rat pups were s.c. injected with tianeptine (5 or 10mg/kg; 10 ml/kg) or equivalent volume of saline solution (control group). When the animals were 25-30 days old, CSD was recorded on the brain cortical surface. In the well-nourished rats, but not in the malnourished group, systemic tianeptine dose-dependently increased the CSD propagation velocity, with 10mg/kg producing a significant (P<0.05) effect. An experiment in adult rats showed that cortical topical application of tianeptine solutions (5mg/ml, 10mg/ml, and 20mg/ml) increased the CSD propagation in both the well-nourished and early-malnourished conditions. In well-nourished animals, 0.5mg/ml topical tianeptine did not affect CSD propagation, and 2mg/ml produced a small, but significant CSD acceleration. Our results indicate a facilitating action of tianeptine on CSD propagation, probably via tianeptine's pharmacological action on the serotonin system. These findings support previous data suggesting an antagonistic role of the serotoninergic system on CSD.
L-Arginine (ARG) is the precursor of the nitric oxide (NO) synthesis. NO-mediated signaling seems to be involved in the phenomenon of cortical spreading depression (CSD). Here, well-nourished and malnourished rats were treated, by gavage, with 150, 300 or 450 mg/kg/day of L-arginine from postnatal days 7-28, and CSD propagation was analyzed at 30-40 days. Compared to non-treated ('naïve') and water-treated controls, ARG-treated rats dose-dependently displayed higher CSD-velocities (P<0.05). In the malnourished rats, only the highest ARG-dose (450 mg/kg/day) increased CSD velocities. The mean +/- SD CSD-velocities (in mm/min) were: for well-nourished rats, 3.77 +/- 0.15, 3.78 +/- 0.23, 4.03 +/- 0.16, 4.36 +/- 0.19 and 4.41 +/- 0.26, in the naïve-, water-controls, 150, 300 and 450 mg/kg/day ARG-groups, respectively; for the same conditions in the malnourished rats, the velocities were 4.18 +/- 0.13, 4.22 +/- 0.09, 4.24 +/- 0.10, 4.27 +/- 0.21 and 4.64 +/- 0.22, respectively. Results demonstrate a dose- and nutrition-dependent CSD-facilitation by L-arginine administered during brain development. It is suggested that this effect is due to the modulation of nitric oxide synthesis.
In the rat, we previously demonstrated that serotonin-enhancing drugs impair cortical spreading depression (CSD) and that l-arginine (arginine) treatment enhances CSD. Here, we investigated the interaction between topical application of the serotonin uptake enhancer tianeptine and systemic arginine administration on CSD. From postnatal day 7-28, female Wistar rats (n=40) received by gavage 300mg/Kg/day arginine (n=20) or water (n=20). Half of the arginine- or water-treated rats underwent CSD recording at 30-40days of age (young), while the other half was recorded at 90-120days (adult). Following baseline recording (four episodes of CSD), we applied tianeptine solution (10mg/ml) to a rectangular portion of the intact dura mater for 10-min and then elicited CSD. This procedure was repeated three times. Compared to baseline values, CSD velocities and amplitudes following tianeptine application increased, and CSD duration decreased significantly (p<0.05) in both young and adult rats, regardless of treatment group. CSD acceleration caused by systemic treatment with arginine is in agreement with previous findings. Topical cortical application of tianeptine replicated the effect of systemic application, suggesting a cortically based mechanism for tianeptine's action. However, the absence of interaction between arginine and tianeptine treatments suggests that they probably act through separate mechanisms.
CSD velocity changes observed in adulthood were associated with the hypercaloric dietary treatment during brain development, constituting evidence in favor of permanent or at least long-lasting electrophysiological effects related to the prevailing nutritional status during the period of brain growth spurt.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.