Lactation in large litters influences anxiety, memory, and spreading depression in adult male rats that were chronically subjected to a non-convulsive pilocarpine dose.

Objectives: Unfavorable lactation influences brain excitability and behavioral reactions in adults. Administration early in life of the cholinergic agonist, pilocarpine, even at non-convulsive doses, alters the brain excitability-related phenomenon known as cortical spreading depression (CSD), and produce anxiogenic-like behavior. However, the influence of unfavorable lactation on the CSD- and memory-effects of pilocarpine administration late in life has not been investigated. Herein, we analyzed the ponderal, electrophysiological (CSD), and behavioral effects of chronic treatment with a non-convulsive dose of pilocarpine, in adult rats suckled under favorable and unfavorable conditions.Methods: Wistar rats were suckled in litters with 9 or 15 pups (groups L9 and L15, respectively). A very low dose of pilocarpine (45/mg/kg/day) was chronically administered in mature rats from postnatal day (PND) 69-90. Behavioral tests occurred at PND91 [elevated plus maze (EPM)], PND93 [open field (OF)], and PND94-95 [object recognition memory (ORM)]. CSD was recorded between PND96-120.Results: Pilocarpine-treated rats performed worse in the anxiety and memory tests, and displayed lower CSD propagation velocity when compared with saline-treated controls. In addition, L15 rats showed an increase in the distance traveled and a decrease in the immobility time in the EPM, impaired ORM, and accelerated CSD propagation when compared with L9 rats (p ≤ 0.05).Discussion: These data suggest that sub-convulsive pilocarpine treatment in adult rats can affect behavioral and excitability-related reactions. In addition, unfavorable lactation increases the ambulatory effects of pilocarpine. Further studies should investigate the possible cholinergic molecular mechanisms involved in these effects.

Monosodium glutamate and treadmill exercise: Anxiety-like behavior and spreading depression features in young adult rats.

OBJECTIVES: The route of administration is an important factor in determining the action of some drugs. We previously demonstrated that subcutaneous monosodium glutamate (MSG) accelerated cortical spreading depression (CSD) in the rat and that treadmill exercise attenuated this effect. This study evaluated whether other routes of administration exert the same action by testing orogastric (gavage) and topical cortical MSG administration in treadmill-exercised and sedentary rats. Additionally, in the orogastric treatment we tested anxiety-like behavior. METHODS: Exercised and sedentary rats received per gavage water or MSG (1 or 2 g/kg) daily from postnatal (P) day 7 to 27. Behavioral tests (open field and elevated plus-maze) occurred at P53 ± 3. At P56 ± 3, we analyzed CSD parameters (velocity, amplitude, and duration of the negative potential change). Other three groups of rats received an MSG solution (25, 50 or 75 mg/ml) topically to the intact dura mater during CSD recording. RESULTS: MSG-gavage increased anxiety-like behavior and the CSD velocities compared with water-treated controls (P < 0.05). Exercise decelerated CSD. In contrast to gavage, which accelerated CSD, topical MSG dose-dependently and reversibly impaired CSD propagation, reduced CSD amplitude and increased CSD duration (P < 0.05). CONCLUSIONS: The exercise-dependent attenuation of the effects of MSG confirms our previous results in rats treated subcutaneously with MSG. CSD results suggest two distinct mechanisms for gavage and topical MSG administration. Additionally, data suggest that exercise can help protect the developing and adult brain against the deleterious actions of MSG.

Ovariectomy in the developing rat decelerates cortical spreading depression in adult brain.

The brain of mammals is one important target organ for the action of gonadal steroids and, when occurring during development, this hormonal influence may result in important repercussion on the brain electrophysiological properties at adulthood, some of which depending on the brain excitability. Here we have characterized in early-ovariectomized adult rats the brain ability to propagate the excitability-related phenomenon known as cortical spreading depression (CSD), as an index of the cerebral electrophysiological effects of the early-induced absence of the ovarian hormones. Wistar female rat pups (7-day old) underwent bilateral ovariectomy (Ovx group; n=21) or Sham surgery (Sham group; n=22), or no surgery (Naive group; n=22). When the pups became adult (90-130 days), they were submitted to the recording of CSD (electrocorticogram and slow DC-voltage variation) in two points of the cortical surface during 4h. Compared with both Naïve and Sham controls, bilateral ovariectomy early in life resulted in significantly higher body weights (from days 50-65 onwards) and severely reduced uterus weights at adulthood. Furthermore, in the Ovx animals the amplitudes and durations of the DC-potential changes of CSD were higher, and the CSD propagation velocities were reduced. Another group of rats ovariectomized in adulthood did not present such CSD alterations. It is concluded that ovariectomy during brain development is causally associated with the CSD changes in the adult brain, indicating a long-lasting effect, which we suggest as being related to the long-term suppression of the action of the ovarian hormones on brain excitability.