Methylphenidate treatment affects mitogen-activated protein kinase activation in the striatum of young rats.

OBJECTIVE: Methylphenidate (MPD) is a drug prescribed for the treatment of attention deficit/hyperactivity disorder and its therapeutic effect is attributed to the inhibition of dopamine. METHODS: Young male Wistar rats were administered MPD (1, 2, 5, or 10 mg/kg) once a day or an intraperitoneal injection of saline for 28 days (chronic treatment) or for 1 day (acute treatment). Two hours after the last administration the animals were decapitated and their striatum was dissected. RESULTS: In this work, we show that continued treatment with MPD is capable of modifying the levels of phosphorylation of proteins JNK1/2 (c-Jun amino-terminal kinases 1 and 2) and ERK1/2 (extracellular signal-regulated kinases 1 and 2). Whereas the level of phosphorylation of protein ERK increased significantly, that of proteins JNK1/2 diminished. CONCLUSION: The alteration in the level of activation of mitogen-activated protein kinases can be a molecular mechanism through which MPD exerts its therapeutic effect.

N-methyl-D-aspartate preconditioning improves short-term motor deficits outcome after mild traumatic brain injury in mice.

Traumatic brain injury (TBI) causes impairment of fine motor functions in humans and nonhuman mammals that often persists for months after the injury occurs. Neuroprotective strategies for prevention of the sequelae of TBI and understanding the molecular mechanisms and cellular pathways are related to the glutamatergic system. It has been suggested that cellular damage subsequent to TBI is mediated by the excitatory neurotransmitters, glutamate and aspartate, through the excessive activation of the N-methyl-D-aspartate (NMDA) receptors. Thus, preconditioning with a low dose of NMDA was used as a strategy for protection against locomotor deficits observed after TBI in mice. Male adult mice CF-1 were preconditioned with NMDA (75 mg/kg) 24 hr before the TBI induction. Under anesthesia with O(2)/N(2)O (33%: 66%) inhalation, the animals were subjected to the experimental model of trauma that occurs by the impact of a 25 g weight on the skull. Sensorimotor gating was evaluated at 1.5, 6, or 24 hr after TBI induction by using footprint and rotarod tests. Cellular damage also was assessed 24 hr after occurrence of cortical trauma. Mice preconditioned with NMDA were protected against all motor deficits revealed by footprint tests, but not those observed in rotarod tasks. Although mice showed motor deficits after TBI, no cellular damage was observed. These data corroborate the hypothesis that glutamatergic excitotoxicity, especially via NMDA receptors, contributes to severity of trauma. They also point to a putative neuroprotective mechanism induced by a sublethal dose of NMDA to improve motor behavioral deficits after TBI.

Rivastigmine reverses habituation memory impairment observed in sepsis survivor rats.

The objective of this study was to evaluate the rivastigmine effect on habituation to the open-field memory impairment observed in sepsis survivor rats. A prospective, controlled experiment was designed. The setting was an animal basic science laboratory, and the subjects were male Wistar rats weighing 300 to 350 g. Rats underwent cecal ligation and puncture (CLP; sepsis group) with "basic support" (saline at 50 mL kg(-1) immediately and 12 h after CLP plus ceftriaxone at 30 mg kg(-1) and clindamycin at 25 mg kg(-1) 6, 12, and 18 h after CLP) or sham-operated (control group). Three days after surgery (1 week before the start the behavior procedure), treatment with rivastigmine was started. Ten days after surgery, animals were submitted to the habituation to an open-field memory test. In the test session, there was a significant reduction in both crossings and rearings in the sham and sepsis group that received rivastigmine when compared with the training, indicating memory acquisition. In contrast, in the sepsis group that did not receive rivastigmine there was no difference in crossings and rearings between training and test session, indicating an impairment in memory acquisition. Therefore, rivastigmine reversed cognitive impairment in sepsis survivor rats in the open-field test.

Chronic mild stress paradigm reduces sweet food intake in rats without affecting brain derived neurotrophic factor protein levels.

Major depression is a common, serious and recurrent disorder that affects 17-20% of the population of the world. The chronic mild stress (CMS) model has been used as an animal model of depression but reflect anhedonia in animals. Present study investigated behavioral, physiological and neurochemical aspects of rats exposed to a CMS procedure. The consumption of sweet food, locomotor activity, body and adrenal gland weight, BDNF protein levels evaluated in hippocampus, cerebrospinal fluid and serum were assessed in rats. Our findings demonstrated decreased in sweet food intake, increase of adrenal gland weight and a decrease of body weight and no changes were observed in BDNF protein levels in serum, cerebrospinal fluid and hippocampus in rats subjected to CMS procedure. Indeed, locomotor activity was not significantly affected. In conclusion, these data reveal that BDNF protein levels were not significantly correlated with the decrease of sweet food consumption observed in CMS exposed animals.