Repeated exposure attenuates the behavioral response of rats to static high magnetic fields

Exposure of rats to high strength static magnetic fields of 7 T or above has behavioral effects such as the induction of locomotor circling, the suppression of rearing, and the acquisition of conditioned taste aversion (CTA). To determine if habituation occurs across magnetic field exposures, rats were pre-exposed two times to a 14 T static magnetic field for 30 min on two consecutive days; on the third day, rats were given access to a novel 0.125% saccharin prior to a third 30-min exposure to the 14 T magnetic field. Compared to sham-exposed rats, pre-exposed rats showed less locomotor circling and an attenuated CTA. Rearing was suppressed in all magnet-exposed groups regardless of pre-exposure, suggesting that the suppression of rearing is more sensitive than other behavioral responses to magnet exposure. Habituation was also observed when rats underwent pre-exposures at 2-3 h intervals on a single day. Components of the habituation were also long-lasting; a diminished circling response was observed when rats were exposed to magnetic field 36 days after 2 pre-exposures. To control for possible effects of unconditioned stimulus pre-exposure, rats were also tested in a similar experimental design with two injections of LiCl prior to the pairing of saccharin with a third injection of LiCl. Pre-exposure to LiCl did not attenuate the LiCl-induced CTA, suggesting that 2 pre-exposures to an unconditioned stimulus are not sufficient to explain the habituation to magnet exposure. Because the effects of magnetic field exposure are dependent on an intact vestibular apparatus, and because the vestibular system can habituate to many forms of perturbation, habituation to magnetic field exposure is consistent with mediation of magnetic field effects by the vestibular system.     

Baicalin prevents the production of hydrogen peroxide and oxidative stress induced by Aβ aggregation in SH-SY5Y cells

This study examined whether rats can simultaneously learn to associate lithium chloride (LiCl)-induced nausea with both contextual and intravascular taste cues. During the conditioning phase (4 days, 72 h apart), 32 male Long Evans rats were injected intraperitoneally with either isotonic saline (NaCl), lithium chloride (LiCl, 127 mg/kg), saline plus 2% saccharin (NaCl + Saccharin), or lithium chloride plus 2% saccharin (LiCl + Saccharin) immediately prior to a 30 min exposure to a novel context. 72 h following the final conditioning day, each animal was re-exposed to the context on a drug-free test day. The next day, animals received a 24 h 2-bottle preference test with a choice between water and a palatable saccharin solution. Results showed that animals treated with LiCl during conditioning, with or without saccharin, displayed significantly higher levels of conditioned gaping responses, indicative of nausea, upon re-exposure to the context, relative to NaCl and NaCl + Saccharin controls. Animals administered LiCl + Saccharin during conditioning also displayed significant conditioned taste avoidance to the saccharin solution during the two bottle choice test. These results indicate that systemic administration (intraperitoneal) of a LiCl + Saccharin solution is effective in simultaneously conditioning toxin elicited nausea to both internal (taste) and external (context) cues.     

Ondansetron blocks LiCl-induced conditioned place avoidance but not conditioned taste/flavor avoidance in rats

The ability of an experimental agent to support conditioned taste/flavor avoidance (CT/FA) in rats often is interpreted as sufficient evidence that the agent produced a state of malaise or nausea. Paradoxically, however, CT/FA also is induced by certain drugs that support conditioned preferences in rats, suggesting that CT/FA is insufficient to reveal a negative hedonic state. The present study tested the hypothesis that the anti-nausea drug ondansetron (OND) would block the ability of nauseogenic lithium chloride (LiCl) to support conditioned place avoidance (CPA), without attenuating LiCl-induced CT/FA. After pre-treatment with either OND or vehicle, rats were conditioned with i.p. injection of 0.15 M LiCl containing 2% saccharin (LiCl + sac) on conditioning day 1, and with 0.15 M NaCl alone on conditioning day 2. Rats were confined to a distinct chamber of a CPA apparatus after each conditioning injection. In other rats, OND or vehicle pre-treatment was followed by NaCl + sac on conditioning day 1, and LiCl alone on day 2. Subsequent testing revealed that OND blocked the ability of LiCl to support CPA. Conversely, in the same rats, OND did not alter the ability of LiCl to condition avoidance of 0.2% sac solution during a 60 min bottle test. In a separate experiment, a sensitive 2-bottle choice test was used to confirm that OND pre-treatment does not reduce the ability of LiCl to support CT/FA. These results support the view that CPA is an additional useful tool to reveal the experience of malaise and nausea in rats, whereas CT/FA demonstrated in bottle intake tests is insufficient for this purpose.     

Responsiveness to methamphetamine in adulthood is altered by prenatal exposure in rats

Methamphetamine (MA) is a drug causing potent psychomotor activation. The aim of the present study was: (1) to assess the effect of prenatal and acute MA administration on behavior in adult male rats and (2) to find out if the prenatal exposure to MA increases sensitivity to acute MA application in adulthood.Behavior of adult male rats prenatally exposed to MA (5 mg/kg) or saline was tested in Open field (OF) and Elevated plus maze (EPM). Subcutaneously administered MA (1 mg/kg) or saline were used as challenge in adulthood, 30 min prior to testing.Our results showed that prenatal MA did not have an effect on baseline behavior in either of the tests. By contrast, acute MA increased overall psychomotor activity by increasing locomotion and exploratory behavior and decreasing comforting behavior. Moreover, adult rats prenatally exposed to MA exhibited increased sniffing and decreased rearing after acute MA dose in adulthood relative to prenatally saline-exposed rats. In addition, while acute MA application decreased anxiety in rats prenatally exposed to MA, rats prenatally exposed to saline were less sensitive to the anxiolytic effects of MA.Our results indicate that changes caused by prenatal exposure to psychostimulants may become apparent as different reactivity to drugs of abuse when an individual encounters them later in life. In addition, we found that the anxiolytic effect of acute MA (1 mg/kg) probably depends also on the reactivity to stress and the activity of hypothalamo-pituitary-adrenal axis.     

Differential effects of osmotic and SSR149415 challenges in maternally separated and control rats: The role of vasopressin on spatial learning

Maternal separation (MS) has been demonstrated to up-regulate the hypothalamic vasopressin (VP) system. Intracerebrally released VP has been demonstrated to affect several types of animal behaviour, such as active/passive avoidance, social recognition, and learning and memory. However, the role of VP in spatial learning remains unclear. In the present study, we investigated the effects of an osmotic challenge and a V1b receptor-specific (V1bR) antagonist, SSR149415, on spatial learning of maternally separated and animal facility reared (AFR) adult male Wistar rats. The osmotic challenge was applied by injecting a hypertonic saline solution, 1 h before the Morris water maze test (MWM). V1bR antagonist SSR149415 (5 mg/kg) was injected i.p. twice (1 h and 30 min) previous to the MWM. A combined treatment with both osmotic challenge and the SSR149415 was applied to the third group whereas rats for basal condition were injected with isotonic saline. Under basal condition no differences between AFR and MS groups were observed. MS rats showed severe impairment during the MWM after the osmotic challenge, but not after the administration of SSR149415. For AFR rats, the opposite phenomenon was observed. The joint application of SSR149415 and osmotic challenge restored the spatial learning ability for both groups. The differential impairment produced by osmotic stress-induced up-regulation and SSR149415 induced V1bR blockage in MS and control rats suggested that VP involvement in spatial learning depends on the individual intrinsic ligand-receptor functional state.     

Effects of electrolytic lesion of dorsolateral periaqueductal gray on analgesic response of morphine microinjected into the nucleus cuneiformis in rat

The periaqueductal gray (PAG) and nucleus cuneiformis (CnF), like the rostral ventromedial medulla, have functional roles in descending pain-inhibitory pathway related to morphine antinociception. There is not any evidence concerning the role of different regions of the PAG on antinociceptive effect of morphine administered into the CnF in pain modulatory system. In the present study, we investigate whether electrolytic lesion of dorsolateral periaqueductal gray (dl-PAG) influence the analgesic effect of morphine microinjected into the CnF. 71 adult male Wistar rats weighting 230–280 g cannulated bilaterally into the CnF, concurrently lesion of dl-PAG was done. The tail-flick and formalin tests were performed to measure pain and antinociceptive effect of morphine microinjected into the CnF (2.5 μg/0.3 μl saline per side). The tail-flick latency was measured at 15, 30, 45, 60 and 75 min following morphine microinjection. In formalin test, pain behavior was recorded for 60 min in early (0–5 min) and late (15–60 min) phases after formalin injection. Each rat was given a subcutaneous 50-μl injection of formalin 2.5% into plantar surface of hind paw following morphine administration. The results showed that dl-PAG lesion attenuated the effect of morphine microinjected into the CnF both in tail-flick and formalin tests while dl-PAG lesion solely did not alter basal pain behavior as compared to control group. In conclusion, our results suggest the existence of a direct or indirect projection from CnF to the dl-PAG at least at the level of the morphine antinociception in pain modulation.     

Early malnutrition,but not age,modulates in the rat the l-Arginine facilitating effect on cortical spreading depression

Nutritional factors acting during brain development can permanently alter brain electrophysiology. l-Arginine is the precursor of nitric oxide synthesis, which can modulate brain function. Here we investigated the effect of early-in-life administration (during postnatal days 7–28) of l-Arginine (300 mg/(kg day)) on cortical spreading depression (CSD), recorded in well-nourished and malnourished (large litters technique) rats aged 30–40 days (young) and 90–110 days (adult). Compared to water-treated controls, well-nourished l-Arginine-treated rats, but not the malnourished ones, displayed higher CSD velocities (P < 0.05) at both ages. The mean ± S.D. CSD velocities (in mm/min) were: for water- and l-Arginine well-nourished rats, 3.78 ± 0.23 and 4.36 ± 0.19 (young groups), and 3.28 ± 0.16 and 4.09 ± 0.30 (adult); for the same conditions in the malnourished rats, 4.22 ± 0.09 and 4.27 ± 0.21 (young), and 4.11 ± 0.18 and 4.21 ± 0.33 (adult). l-Arginine treatment did not affect body and brain weights. It is concluded that early l-Arginine treatment long lastingly increased brain CSD-susceptibility and this effect is abolished by early malnutrition.     

A novel animal model to evaluate the ability of a drug delivery system to promote the passage through the BBB

The purpose of this investigation was to explore the potentiality of a novel animal model to be used for the in vivo evaluation of the ability of a drug delivery system to promote the passage through the blood–brain barrier (BBB) and/or to improve the brain localization of a bioactive compound. A Tween 80^®-coated poly-l-lactid acid nanoparticles was used as a model of colloidal drug delivery system, able to trespass the BBB. Tacrine, administered in LiCl pre-treated rats, induces electrocorticographic seizures and delayed hippocampal damage. The toxic effects of tacrine-loaded poly-l-lactid acid nanoparticles (5 mg/kg), a saline solution of tacrine (5 mg/kg) and an empty colloidal nanoparticle suspension were compared following i.p. administration in LiCl-pre-treated Wistar rats. All the animals treated with tacrine-loaded nanoparticles showed an earlier outcome of CNS adverse symptoms, i.e. epileptic onset, with respect to those animals treated with the free compound (10 min vs. 22 min respectively). In addition, tacrine-loaded nanoparticles administration induced damage of neuronal cells in CA1 field of the hippocampus in all treated animals, while the saline solution of tacrine only in 60% of animals. Empty nanoparticles provided similar results to control (saline-treated) group of animals. In conclusion, the evaluation of time-to-onset of symptoms and the severity of neurodegenerative processes induced by the tacrine–lithium model of epilepsy in the rat, could be used to evaluate preliminarily the capability of a drug delivery system to trespass (or not) the BBB in vivo.     

Hypocapnia-dependent facilitation of augmented breaths: observations in awake vs. anesthetized rats

We investigated whether commonly used injectable laboratory anesthetics alter the regulation of augmented breaths (ABs) in different respiratory backgrounds. Male rats were studied on three separate experimental days, receiving one of three injections in randomized order: ethyl carbamate (‘urethane’; 1.2 mg kg⁻¹), ketamine/xylazine (ket/xyl; 80/10 mg kg⁻¹), or normal saline. Following each of the three interventions, breathing was monitored during 15 min exposures to normoxia (room air), hypoxia (10% O₂) and hypoxia + CO₂ (10% O₂, 5% CO₂). Urethane anesthesia completely eliminated ABs from the breathing rhythm in room air conditions (p < 0.001), and decreased the hypocapnia-dependent component of this response (p < 0.001). ket/xyl left the normal incidence of ABs in room air breathing intact but significantly suppressed the hypoxia-induced facilitation of ABs (p = 0.0015). These results provide the first clear evidence that laboratory anesthesia can profoundly alter the regulation of ABs including the hypocapnia-dependent component of their facilitation.     

Effect of nitric oxide synthase inhibitor and NMDA receptor antagonist on the development of nicotine sensitization of nucleus accumbens dopamine release: An in vivo microdialysis study

We have previously found that the neuronal nitric oxide synthase inhibitor N-nitro-l-arginine (l-NNA) and the noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 prevent behavioral sensitization to nicotine. This study aimed to investigate the effect of l-NNA and MK-801 on a neurochemical component of nicotine sensitization by evaluating the effect of the drugs on nicotine sensitization of nucleus accumbens dopamine (DA) release. Sprague–Dawley rats were pretreated with l-NNA (15 mg/kg, i.p.), MK-801 (0.3 mg/kg, i.p.), or saline 30 min before injection of nicotine (0.4 mg/kg, s.c., once daily) for seven consecutive days. Twenty-four hours after the last drug injection, animals were challenged with local perfusion of 5 mM nicotine into the shell of nucleus accumbens for 60 min and DA release was monitored using in vivo microdialysis. In rats treated with repeated nicotine, acute nicotine challenge induced a greater increase of accumbal DA release than in saline-treated animals (maximal DA response = 969 ± 235% (mean ± S.E.M.) of basal level versus 520 ± 93%, p = 0.042). Co-administration of l-NNA or MK-801 with nicotine attenuated an increase of DA release elicited by acute nicotine challenge, compared with nicotine alone (maximal DA response = 293 ± 58% and 445 ± 90% of basal level, respectively versus 969 ± 235%, p = 0.004 and p = 0.013, respectively). These data demonstrate that l-NNA and MK-801 block the development of nicotine sensitization of nucleus accumbens DA release, further supporting the involvement of nitric oxide and NMDA receptors in the development of behavioral sensitization to nicotine.     

Different responses of nitric oxide synthase inhibition on morphine-induced antinociception in male and female rats

The roles of gonadal hormones and nitric oxide on pain perception and their interaction have been widely investigated. In the present study the chronic effect of l-NAME (NOS inhibitor) on morphine-induced antinociception in male and female rats was investigated. Forty rats were divided into four groups: (1) female (2) female-LN (3) male (4) and male-LN. The animals of groups 2 and 4 received daily injection of l-NAME (10 mg/kg) during 3 weeks. The animals of control groups 1 and 3 received 2 ml/kg saline instead of l-NAME. Finally, all animals were tested on the hot plate test (52 ± 0.2 °C; Cut-off 80 s) to evaluate the antinociceptive effects of morphine. The hot plate test was performed for base record 15 min before the injection of morphine (10 mg/kg; s.c.) and consequently it was repeated every 15 min after the injection. There were no significant differences in baseline latencies among all groups. Reaction times after injection of morphine in female-LN were higher than in the female control group (p < 0.01). There was, however, no significant difference between male control and male-LN groups. Reaction times in the female-LN group were significantly higher than in the male-LN group. Reaction times after injection of morphine in the male group was longer than in the female group (p < 0.01). It is concluded that sex hormones such as testosterone and estrogen have a role in pain perception and analgesia. NO has a modulatory effects on functions of sex hormones in pain perception and analgesic effects of opioids.     

Melatonin ameliorates neocortical neuronal dendritic impairment induced by toluene inhalation in the rat

The present study investigated the effects of toluene inhalation and the restorative effects of melatonin on branching and basal dendritic outgrowth of superficial pyramidal neurons in rat’s frontal, parietal, and occipital cortices. At postnatal day 21 (P21), Sprague-Dawley male rats were randomly assigned to either an air-only group or a toluene group. From P22 to P32 the animals were exposed to either clean air or toluene vapors (5000-6000 ppm) for 10 min/day. This strategy simulated common toluene abuse in humans, which consists of 15-20 rapid inhalations of highly concentrated solvent. Once the inhalation period was over (P32), toluene exposed animals were randomly reassigned to one of following experimental groups: (i) air-control/saline; (ii) toluene/saline; (iii) toluene/melatonin 0.5 mg/kg; (iv) toluene/melatonin 1.0 mg/kg; (v) toluene/melatonin 5.0 mg/kg; and (vi) toluene/melatonin 10 mg/kg. Seven days after the last inhalation (P39), all the animals were sacrificed under deep anesthesia; brains were dissected out and stained according to the Golgi-Cox-Sholl procedure. Layer II/III pyramidal neurons were morphologically analyzed by measuring their basilar dendritic length and the number of branches. The results obtained revealed that (i) toluene inhalation significantly reduced dendritic outgrowth and branching in all cortical areas studied, and (ii) intraperitoneal administration of melatonin (0.5-10 mg/kg) was able to restore the dendritic impairment induced by toluene exposure.     

Nervous control of the release of neurotensin-like immunoreactivity from the small intestine of the rat

Intraduodenal administration of oleic acid increased plasma neurotensin-like immunoreactivity (p-NTLI). The integrated responses to saline and oleic acid were 5.7 and 9.7 nM0-180 min, respectively. The integrated response was not significantly altered by i.v. administration of atropine, guanethidine, mepyramine, cimetidine, methysergide or a substance P antagonist, but it was abolished by hexamethonium and morphine (5.9 and 6.3 nM0-180 min, respectively). An exogenous supply of bile and pancreatic juice did not alter the integrated response in morphine- and hexamethonium-treated rats. Haloperidol significantly increased the p-NTLI response to oleic acid (13 nM0-180 min). The results suggest that the release of neurotensin is influenced by nervous pathways involving nicotinic and opioid receptors. Catecholamines and 5-HT receptors may exert an inhibitory influence on the release of NTLI.     

Adverse experience during early life and adulthood interact to elevate tph2 mRNA expression in serotonergic neurons within the dorsal raphe nucleus

Anxiety disorders, depression and animal models of vulnerability to a depression-like syndrome have been associated with dysregulation of brain serotonergic systems. These effects could result from genetic influences, adverse early life experiences (ELE), or acute stressful life events, all of which can alter serotonergic neurotransmission and have been implicated in determining vulnerability to neuropsychiatric disorders. To evaluate the effects of ELE, adverse experiences during adulthood, and potential interactions between these factors on neuronal tryptophan hydroxylase 2 (tph2) mRNA expression, we investigated in rats the effects of maternal separation (MS)(separation from the dam for 180 min/day from postnatal day 2–14; MS180, a model of vulnerability to a depression-like syndrome), neonatal handling (separation from the dam for 15 min/day from postnatal day 2–14; MS15, a model of decreased stress sensitivity), or normal animal facility rearing (AFR) control conditions, with or without subsequent exposure to adult social defeat, on tph2 mRNA expression in the dorsal raphe nucleus (DR). Among rats exposed to social defeat, MS180 rats had increased tph2 mRNA expression in the DR, while MS15 rats had decreased tph2 mRNA expression compared to AFR rats. Social defeat increased tph2 mRNA expression, but only in MS180 rats and only in the “lateral wings” of the DR, a subdivision of the DR that is part of a sympathomotor command center. Overall, these data demonstrate that ELE and stressful experience during adulthood interact to determine tph2 mRNA expression. These changes in tph2 mRNA expression represent a potential mechanism through which adverse ELEs and stressful life experiences during adulthood may interact to increase vulnerability to stress-related psychiatric disease.     

Impaired hypoxic ventilatory response following neonatal sustained and subsequent chronic intermittent hypoxia in rats

Neonatal chronic intermittent hypoxia (CIH) enhances the ventilatory sensitivity to acute hypoxia (acute hypoxic ventilatory response, HVR), whereas sustained hypoxia (SH) can have the opposite effect. Therefore, we investigated whether neonatal rats pre-treated with SH prior to CIH exhibit a modified HVR. Rat pups were exposed to CIH (5% O₂/5 min, 8 h/day) between 6 and 15 days of postnatal age (P6-15) after pre-treatment with either normoxia or SH (11% O₂; P1-5). Using whole-body plethysmography, the acute (5 min, 10% O₂) HVR at P16 (1 day post-CIH) was unchanged following CIH (67.9 ± 6.7% above baseline) and also SH (58.8 ± 10.5%) compared to age-matched normoxic rats (54.7 ± 6.3%). In contrast, the HVR was attenuated (16.5 ± 6.0%) in CIH exposed rats pre-treated with SH. These data suggest that while neonatal SH and CIH alone have little effect on the magnitude of the acute HVR, their combined effects impose a synergistic disturbance to postnatal development of the HVR. These data could provide important insight into the consequences of not maintaining adequate levels of oxygen saturation during the early neonatal period, especially in vulnerable preterm infants susceptible to frequent bouts of hypoxemic events (CIH) that are commonly associated with apnea of prematurity.     

Plasma testosterone concentration in adult male rats following acquisition of copulation-illness associations.

Prior research has identified stimuli and procedures that elicit increments in plasma testosterone in copulating male rats. In the present experiment, we demonstrate that associative inhibition of copulatory behaviors in male rats is not correlated with and cannot be attributed to a conditioned suppression of testosterone. Each male rat was paired with an inaccessible estrous female for 7 min and was then given an opportunity to copulate. Two groups received an injection of either lithium chloride (LiCl; 0.3 M, 20 ml/kg, IP) or saline (0.3 M, 20 ml/kg, IP) immediately after each of 11 pairings spaced at 3- to 4-day intervals. A third group received a noncontingent injection of LiCl 24 h after each pairing. After an initial screening for copulatory behaviors, a fourth group received only handling comparable to that received by the other three groups. Rats that received contingent LiCl gradually ceased to copulate; rats that received either noncontingent LiCl or saline remained vigorous copulators. Male rats were returned to their home cages on Trial 12 after 7-min exposure to an inaccessible female. Blood was collected by decapitation 38 min later. Testosterone levels, measured by radioimmunoassay, were significantly higher for saline than for handled control rats. Testosterone levels for handled control rats, however, were comparable to those of copulating and noncopulating rats that had received either noncontingent or contingent LiCl, respectively.     

Maternal separation alters serotonergic transporter densities and serotonergic 1A receptors in rat brain

RATIONALE: The basic mechanisms underlying the association between early life maternal separation and adulthood psychiatric disorders are largely unknown. One possible candidate is the central serotonergic system, which is also abnormal in psychiatric illnesses. Neuroadaptational changes in serotonergic transporter and serotonergic 1A receptors may underlie links between early life stress and adulthood psychiatric disorders. OBJECTIVE: The aim of this study was to investigate the consequences of a rat model of maternal separation on serotonergic transporter and serotonergic 1A receptor densities and function in adult rat forebrain. METHODS: Rat pups were separated from dams from postnatal day 2 to postnatal day 14, each day, for zero time, 15 min and 180 min to determine the time-course of effects. A non-handled group was added to control for the effects of handling by an experimenter compared with the animal facility-reared group. Quantitative [(125)I]3beta-(4-iodophenyl)tropan-2beta-carboxylic acid methyl ester and [(125)I]-mPPI autoradiography was used to determine serotonergic transporter and serotonergic 1A densities, respectively. Adult rats were challenged with saline or serotonergic 1A agonist (+) 8-hydroxy-2-(di-n-propylamino)tetralin, 0.4 mg/kg, s.c.) and plasma adrenocorticotropic hormone and corticosterone were determined. RESULTS: serotonergic transporter and serotonergic 1A densities were significantly lower in the non-handled group in the paraventricular, arcuate, dorsomedial and ventromedial nuclei of the hypothalamus. The non-handled group also displayed lower serotonergic transporter and serotonergic 1A densities in the basolateral anterior, basolateral ventral and basomedial amygdaloid nuclei. Serotonergic transporter densities were also decreased in the CA3 area of the hippocampus in the non-handled group. In contrast, the maternal separation 15 min group displayed the highest serotonergic transporter and serotonergic 1A densities in the basomedial nucleus of amygdala, basolateral anterior nucleus of amygdala, basolateral ventral nucleus of amygdala and basomedial nucleus of amygdala amygdaloid nuclei. CONCLUSIONS: Early life maternal separation and the extent of handling can alter adult brain serotonergic transporter and serotonergic 1A levels and function in the forebrain. Alterations in these serotonergic systems by early rearing conditions might increase vulnerability for behavioral disorders in adulthood.     

Choline acetyltransferase and acetylcholinesterase activities are reduced in rat striatum and frontal cortex after pilocarpine-induced seizures

In the present study we investigated the alterations on choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities in rat striatum and frontal cortex caused by pilocarpine-induced seizures. Wistar rats were treated with 0.9% saline (i.p., control group), with the association of 0.9% saline (i.p.) plus pilocarpine (400 mg/kg, i.p.), 30 min before of administration of saline (pilocarpine group). After the treatments all groups were observed for 1 h. The ChAT and AChE activities were measured using spectrophotometric methods and the results compared to values obtained from saline-treated animals. In pilocarpine group was observed a significantly decreases in ChAT and AChE activities in striatum and frontal cortex of adult rats, when compared to control group. Results showed that during acute phase of seizures striatal and frontal cortex ChAT and AChE activities are diminished. Our findings suggest that seizures caused cognitive dysfunction and decreases of ChAT and AChE activities that might be related, at least in part, to the neurological problems presented by epileptic patients.     

Molecular and electrophysiological changes in the prefrontal cortex-amygdala-dorsal periaqueductal grey pathway during persistent pain state and fear-conditioned analgesia

Fear-conditioned analgesia (FCA) is the reduction in pain responding which is expressed upon re-exposure to a context previously paired with an aversive stimulus. Projections along the prefrontal cortex (PFC)-amygdala-dorsal periaqueductal grey (dPAG) pathway may mediate FCA. However, there is a paucity of studies measuring both molecular and electrophysiological changes in this pathway in rats expressing persistent pain-related behaviour or FCA. Male Lister-hooded rats, with stimulating and recording electrodes implanted in the amygdala and dPAG, respectively, either received or did not receive footshock (0.4 mA) paired with context, followed 23.5 h later by an intraplantar injection of saline or formalin (50 μL, 2.5%) into the right hindpaw. Thirty minutes post-formalin/saline, rats were re-exposed to the context for 15 min, during which pain-related behaviours were assessed in addition to evoked field potential recordings in the amygdala-dPAG pathway. Immediately after the 15-minute trial, PFC tissue was isolated for measurement of total and phosphorylated extracellular-signal regulated kinase (ERK) by western blotting. Formalin-evoked nociceptive behaviour in non-fear-conditioned rats was associated with increased field potential amplitude in the dPAG and increased relative expression of phospho-ERK in the PFC. These effects were abolished in rats expressing FCA. Fear conditioning in non-formalin treated rats was associated with increased phospho-ERK in the PFC but no change in field potential amplitude in the dPAG. Together, these data suggest differential, state-dependent alterations in electrophysiological activity and ERK phosphorylation along the PFC-amygdala-dPAG pathway during pain, conditioned fear, and FCA.     

Anxiety-like behavior in weanling and young adult male and female malnourished rats

The present study determined whether protein-calorie malnutrition alters anxiety-like behavior in weanling and young adult, male and female malnourished rats. On the day of birth, litters of Wistar rats were divided into Control (C) and Malnutrition (M) groups. In the C group, litters were fed by dams receiving ad libitum lab chow, whereas in the M group, litters were fed by dams receiving 40% of the total amount of the diet offered to dams in the C group. After weaning (PND21) until PND50, animals received the same food as theirs mothers (i.e., ad libitum access in the C group and 40% of the C group food in the M group). On PND21 and PND50, independent C (male [CM] and female [CF]) and M (male [MM] and female [MF]) groups were exposed to the elevated T-maze. The time taken to withdraw four paws from this arm was recorded (baseline latency [BL]). The same measurement was repeated twice at 30 s intervals (avoidance trial 1 [AT1] and avoidance 2 [AT2]). The cutoff time in each trial was 300 s. ANOVA indicated a four-way age × diet × sex × trials interaction. Post hoc comparisons revealed that PND50 rats had a lower BL and AT1 latency compared with PND21 rats. Training increased both AT1 and AT2 latencies compared with BL in both the CM and CF groups. Weanling malnourished rats exhibited reduced anxiety-like behavior and young adult male rats presented less anxiety-like behavior than young adult female rats in this experimental model.