Neonatal administration of citalopram delays somatic maturation in rats

We investigated the somatic maturation of neonate rats treated during the suckling period with citalopram, a selective serotonin reuptake inhibitor. Groups with 6 male neonates were randomly assigned to different treatments 24 h after birth. Each litter was suckled by one of the dams until the 21st postnatal day. Body weight, head axis and tail length were measured daily from the 1st to the 21st postnatal day. Time of ear unfolding, auditory conduit opening, incisor eruption, and eye opening was determined. Pups received 5 mg (Cit5), 10 mg (Cit10) or 20 mg/kg (Cit20) citalopram sc, or saline (0.9 percent NaCl, w/v, sc). Compared to saline, body weight was lower (24.04 percent, P < 0.01) for Cit10 from the 10th to the 21st day and for Cit20 from the 6th to the 21st day (38.19 percent, P < 0.01). Tail length was reduced in the Cit20 group (15.48 percent, P < 0.001) from the 8th to the 21st day. A reduction in mediolateral head axis (10.53 percent, P < 0.05) was observed from the 11th to the 21st day in Cit10 and from the 6th to the 21st day in Cit20 (13.16 percent, P < 0.001). A reduction in anteroposterior head axis was also observed in the Cit20 group (5.28 percent, P < 0.05) from the 13th to the 21stday. Conversely, this axis showed accelerated growth from the 12th to the 21stday in the Cit5 group (13.05 percent, P < 0.05). Auditory conduit opening was delayed in the Cit5 and Cit20 groups and incisor eruption was delayed in all citalopram groups. These findings show that citalopram injected during suckling to rats induces body alterations and suggest that the activity of the serotoninergic system participates in growth mechanisms.

Effect of a Brazilian regional basic diet on the prevalence of caries in rats

The aim of the present study was to determine the effect of a regional basic diet (RBD) on the prevalence of caries in the molar teeth of rats of both sexes aged 23 days. The animals were divided into six groups of 10 rats each receiving the following diets for 30 and 60 days after weaning: RBD, a cariogenic diet, and a commercial diet. The prevalence and penetration of caries in the molar teeth of the rats was then analyzed. The RBD produced caries in 37.5 percent of the teeth of animals fed 30 days, and in 83.4 percent of animals fed 60 days, while the cariogenic diet produced caries in 72.5 percent and 77.5 percent of the teeth of animals fed 30 and 60 days, respectively. Rats fed the RBD for 30 days had caries in the enamel in 38 percent of their teeth, 48 percent had superficial dentin caries, and 7.5 percent moderate dentin caries. The effect of the RBD did not differ significantly from that of the cariogenic diet in terms of the presence of caries in rats fed 60 days. The penetration depth of the caries produced by the RBD was the same as that produced by the cariogenic diet. Our results show that the RBD has the same cariogenic potential as the cariogenic diet. Since the RBD is the only option for the low-income population, there should be a study of how to compensate for the cariogenicity of this diet

Reduction of intraspecific aggression in adult rats by neonatal treatment with a selective serotonin reuptake inhibitor

Most studies suggest that serotonin exerts an inhibitory control on the aggression process. According to experimental evidence, this amine also influences growth and development of the nervous tissue including serotoninergic neurons. Thus, the possibility exists that increased serotonin availability in young animals facilitates a long-lasting effect on aggressive responses. The present study aimed to investigate the aggressive behavior of adult rats (90-120 days) treated from the 1st to the 19th postnatal day with citalopram (CIT), a selective serotonin reuptake inhibitor (20 mg/kg, sc, every 3 days). Aggressive behavior was induced by placing a pair of rats (matched by weight) in a box (20 x 20 x 20 cm), and submitting them to a 20-min session of electric footshocks (five 1.6-mA - 2-s current pulses, separated by a 4-min intershock interval). When compared to the control group (rats treated for the same period with equivalent volumes of saline solution), the CIT group presented a 41.4 percent reduction in the duration of aggressive response. The results indicate that the repeated administration of CIT early in life reduces the aggressive behavior in adulthood and suggest that the increased brain serotoninergic activity could play a role in this effect

Spreading depression is facilitated in adult rats previously submitted to short episodes of malnutrition during the lactation period

Lactating rat dams were submitted to short episodes (1,2 or 3 weeks) of nutritional restriction by receiving the "regional basic diet" (RBD), with 8 percent protein) of low-income human population of Northeast Brazil. Their pups were then studied regarding the developmental effects on body and brain weights. When the rats reached adulthood, cortical susceptibility to the phenomenon of spreading depression (SD) was evaluated by performing electrophysiological recordings on the surface of the cerebral cortex. SD was elicited at 20-min intervals by applying 2 percent KCL for 1 min to a site on the frontal cortex and its occurrence was monitored at 2 sites in the parietal region by recording the electrocorticogram and the slow potential change of SD. When compared to control rats fed a commercial diet with 23 percent protein, early malnourished rats showed deficits in body and brain weights (10 percent to 60 percent and 3 percent to 15 percent, respectively), as well as increases in velocity of SD propagation (10 percent to 20 percent). these effects were directly related to the duration of maternal dietary restriction, with pups malnourished for 2 ou 3 weeks presenting more intense weight and SD changes than those malnourished for 1 week. The effects of 1-week restrictions on SD were less evident in the pups malnourished during the second week of lactation and were more evident in pups receiving the RBD during the third week. The results indicate that short episodes of early malnutrition during the suckling period can affect body and brain development, as well as the cortical susceptibility to SD during adulthood. The data also suggest that the third week of lactation is the period during which the brain is most sensitive to malnutrition, concerning the effects on SD.

Effect of aging on cortical spreading depression

The effects of aging on spreading depression (SD) were investigated in the Mongolian gerbil (G; age range 1.5 to 58 months; N = 35) and in the albino rat (R; 2.5 to 24 months; N = 100). Two strains of rats were studied: Wistar (W; N = 35) and Sprague-Dawley (SDAW; N = 65). SDAW rats were divided into two groups: one group was fed a commercial lab chow diet (CD) containing 22 per cent protein (N = 47), and the other was fed a 22 per cent casein diet (CAS; N = 18). SD was elicited on the frontal cortical surface by 1-min application of 2 per cent KCl and its appearance was recorded (ECoG and DC potential) at two points in the parieto-occipital area of the same hemisphere. SD propagation velocity was measured on the basis of the time spent for an SD "wave" to cross the distance between the two recording points. Within the age range studied, older animals displayed significantly lower SD velocities than the younger ones, independent of the species, strain or diet (velocity ranges, in mm/min: G, 2.22-5.99; W, 2.47-4.12; SDAW-CD, 2.32-4.42 and SDAW-CAS, 2.65-4.14). The correlation coefficients between age and SD velocity were: G, -0.78; W, -0.45; SDAW-CD, -0.68 and SDAW-CAS, -0.72 (P<0.05 in all cases). As a rule, at each time point the gerbils presented higher SD velocities than the rats of the same age. In another set of experiments, in order to test the role of free radicals in SD, 7 gerbils (14-51 months old) and 13 W rats (3-24 months old) were fed a 22 per cent casein diet free of the antioxidant vitamins C and E for 4-6 weeks before the experiments. No correlation was found between age and SD propagation in these animals fed a diet free of vitamins C and E, although gerbils displayed higher SD velocities than age-matched rats (velocities: G, 3.70-5.34; R, 3.25-4.44 mm/min; correlation coefficients: G, -0.39; W, -0.29; P>0.05). These data indicate that gerbils have higher SD susceptibility than rats of the same age, and that this susceptibility decreases with aging in both species. The lack of correlation between age and SD velocity in the animals fed a diet free of antioxidant vitamins suggests a possible role of free radicals in cortical SD, in accordance with evidence from other laboratories obtained in the isolated retina.

Effect of d-fenfluramine on cortical spreading depression in rats

We investigated the effect of a single ip injection of ed-fenfluramine (d-fen; 5-10 mg/kg), a serotinin reuptake blocker, on cortical spreading depression (SD) in 17 male Wistar rats (300-360 g body weight). SD was elicited at the right frontal cortex by 1-min application of 2 percent KCl at 20-min intervals. SD propagation was monitored (electrocorticogram and DC-recording) at 2 points on the right parietal surface for 3 h. After a "baseline" recording period (1 h), d-fen was injected and the recording session was continued for 2 h. When compared to the predrug SD velocities (t = 0 min) the values measured after d-fen decreased significantly at t = 20 min (3.44 + or - 0.63 vs 2.66 + or - 0.51 mm/min; N = 17, P<0.001), at t = 40 min (3.32 + or - 0.58 vs 2.53 + or - 0.52 mm/min; N = 14, P<0.001), att=60 min (3.68 + or - 0.63 vs 2.92 + or - 0.72 mm/min; N = 11, P<0.001) and at t = 80 min (3.57 + or - 0.61 vs 3.03 + or - 0.83 mm/min; N = 12, P<0.05) but not at t = 100 min (3.47 + or - 0.72 vs 3.31 + or - 0.88 mm/min; N = 12) nor at t = 120 min (3.44 + or - 0.67 vs 3.37 + or - 0.76 mm/min; N = 11). Furthermore, in 19 of 48 KCl stimulations (40 percent) performed ...

Effect of pre- and postnatal propylthiouracil administration on the propagation of cortical spreading depression of adult rats

The effect of treatment with propylthiouracil early in life (PTU; 8 mg k-1 day-1, ip, from day 17 of gestation to postnatal day 42) on the susceptibility of the cerebral cortex to spreading depression (SD) was studied in 13 adult Wistar rats (90-100 days of age). Ten animals injected with Ringer solution served as control. Adult PTU-treated rats displayed a significant (P < 0.05) reduction in body weight (mean +/- SD: 139.9 +/- 28.9 g vs 304.9 +/- 42.8 g) as well as wet brain weight (1.39 +/- 0.12 g vs 1.86 +/- 0.13 g) and dry brain weight (247.3 +/- 24.2 mg vs 359.4 +/- 30.1 mg). Their thyroid glands presented histological changes indicative of hypofunction and SD velocity of propagation was significantly reduced all along the 6 h of the recording session (mean +/- SD ranges: 1.90 +/- 0.46 to 2.52 +/- 0.68 mm/min vs 3.49 +/- 0.57 to 3.71 +/- 0.55 mm/min). The results indicate that PTU early in life was effective in producing hypothyroidism and that in this situation cortical susceptibility to SD is impaired

Effect of anesthesia on the propagation of cortical spreading depression in rats

The effect of ip anesthesia with urethane + chloralose (U + C, 1,0 g/kg) or thionembutal (TH, 40.0 mg/kg) on the velocity of propagation of cortical spreading depression was studied in adult Wistar rats. We also describe a technique for measuring the spreading depression propagation rate based on implanting insulated silver wires into the right parietal region, whose silver chloride tips are in contact with the cortical surface. The propagation rate was measured in the same animals during (mean ñ SEM, mm/min: 2.69 ñ 0.17 for U C, N =9, and 2.60 ñ 0.09 for TH, N =7) and after (3.23 ñ 0.13 for U C and 3.84 ñ 0.18 for TH) anesthesia. The rate was significantlyhigher for rats in the awake condition. The second administration of anesthesia to the same rats decreased the velocity of spreading depression again (2.01 ñ 0.38 for U + C, N=7, and 2.96 ñ 0.18 for TH, N=7). The effects of TH and U + C on the rate of propagation were reversed 24 and 48 hours after anesthesia, respectively. We conclude that the technique proposed is adequate for measuring the velocity of spreading depression in unanesthetized rats and that U + C and TH reduce the propagation velocity

Diferential effect of changes in blood glucose levels on the velocity of propagation of cortical spreading depression in normal and malnourished rats

The effects of intravenous glucose (1ml,40% solution) and insulin (1.5-3U/Kg in 0.2-0.4 ml Ringer solution) on the velocity of propagation (VP) of cortical spreading depression (SD) were studied in 36 well-nourished (W) and 25 malnourished (M) adult (90 days old) Wistar rats of both sexes. Blood levels, measured 40-70 min after glucose, were increased by 330% in the W group (N = 18) and by 202.9% in the M rats (N=12), when compared to the pre-injection levels. Insulin decreased it by 43.5% and 61.2% in W and M rats, respectively (N=13). In the W rats, SD VP decreased after glucose and increased after insulin. The effect of glucose could not be attributed to increases in blood osmolarity, since iv mannitol (1 ml, 20% solution, N = 5) failed to decrease SD VP. The mean ñ SEM VP before and after the treatments were as follows (in mm/min): W rats, glucose 3.31 ñ 0.16 and 3.11 ñ 0.13; insulin 3.50 ñ 0.12 and 3.81 ñ 0.11; mannitol 3.53 ñ 0.46 and 3.92 ñ 0.48. In the M rats, the above effects on SD were not seen (SD VP: glucose 3.89 ñ 0.20 and 4.13 ñ 0.24; insulin 3.51 ñ 0.19 and 3.63 ñ 0.17). The results suggest that changes in the production of brain energy influence SD propagation

Effect of dietary lithium on cortical spreading depression

The influence of lithium administration on cortical spreading depression (SD) was investigated in rats whelped by dams fed a diet containing lithium (1.5 g/kg) during the gestation or the lactation periods. Velocity of SD propagation was measured when the rats became adults and was similar to that of rats raised on a normal diet. A third group of adult rats received lithium during the three weeks preceding SD recordings and presented a significant reduction in SD velocity as compared to control rats. These data suggest that in adult rat a brief treatment with lithium impairs SD propagation, whreas much earlier treatment does not

Apomorphine does not mimic the effects of rem-sleep deprivation on cortical spreading depression

The propagation of cortical spreading depression (SD) and the incidence of "spontaneous" SD were enhanced in rats after rapid-eye-movement sleep deprivation (REMD) as compared to control animals. Pseudo-deprived rats were similar to controls, suggesting that the facilitatory effect on SD is due to REMD rather than to the stress accompanying deprivation. In control rats, apomorphine (0.5 to 8 mg/kg) failed to reproduce the effects of REMD and also failed to enhance the REMD effects in deprived rats, suggesting that the dopaminergic system does not play an important role in propagation of cortical SD