AMPA receptors are involved in prefrontal direct current stimulation effects on long-term working memory and GAP-43 expression.

Anodal Direct Current Stimulation (DC) over prefrontal cortex improves working memory. This study investigated the influence of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) on prefrontal anodal DC-induced effects on spatial working memory and GAP-43 expression. Male Wistar rats well-trained in radial maze procedures received five sessions of anodal epidural DC stimulation (eDCS: 400 µA, 13 min, one daily session) over the left mPFC, or a respective sham procedure, and afterwards they received a single dose (1 mg/kg) of perampanel (PRP), an AMPARs antagonist, or vehicle 30 min before the performance of 4-h delayed task. The prefrontal cortex (PFC) and hippocampus (HPC) were removed 24-h later and GAP-43 (growth-associated protein) expression was measured by Western blot analysis. Repetitive eDCS decreased the number of errors in the 4-h post-delay performance (p < 0.05) and increased the expression of GAP-43 (p < 0.01) in the PFC when compared to sham stimulation. These behavioral and prefrontal molecular changes induced by the repetitive eDCS seem to involve AMPAR activity, because they were abolished when AMPARs were blocked by PRP (p < 0.01 and 0.05, respectively). Besides, in the HPC, changes of GAP-43 expression induced by eDCS was only seen when AMPARs were blocked by PRP. Therefore, the neuronal plasticity involving AMPARs may underlie, at least in part, the improving of spatial working memory and GAP-43 expression induced by the repetitive anodal prefrontal DC stimulation.

Impairment of spatial working memory and oxidative stress induced by repeated crack cocaine inhalation in rats.

Crack cocaine is a highly toxic drug with great potential to induce addiction. It produces more intense effects than cocaine powder, with its use having grown worldwide. However, few studies have focused on the cognitive and biochemical consequences that result from crack cocaine inhalation. This study examined the effects of direct crack cocaine inhalation on spatial working memory and brain oxidative stress parameters in rats. Male adult Wistar rats, well-trained in an eight-arm radial maze (8-RM), underwent five sessions of crack cocaine inhalation (crack cocaine group) once a day or inhalation simulation (sham group), being tested in 1-h delayed tasks 24 h after the last inhalation. An additional inhalation session was carried out the following day, with the prefrontal cortex, hippocampus and striatum being removed five minutes afterwards in order to assess oxidative damage such as lipid peroxidation, thiobarbituric acid-reactive species (TBARS) levels, and advanced oxidation protein products (AOPP), as well as the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Animals from the crack cocaine group showed more errors (p <  0.01) in the 1-h post-delay performance in the 8-RM when compared to the sham group. The crack cocaine group showed decreased (p <  0.05) lipid peroxidation in the hippocampus and increased (p <  0.001) levels of AOPP and SOD activity (p < 0.05) in the striatum when compared to the sham group. Therefore, the repeated inhalation of crack cocaine impaired long-term spatial working memory and elicited oxidative stress in the hippocampus and striatum of rats.

Anhydroecgonine Methyl Ester (AEME), a Product of Cocaine Pyrolysis, Impairs Spatial Working Memory and Induces Striatal Oxidative Stress in Rats.

When burning crack cocaine, the pyrolysis of cocaine generates anhydroecgonine methyl ester (AEME). AEME has been shown to be highly neurotoxic but its effects on cognitive function and oxidative stress are still unknown. Thus, this study investigated the effects of AEME on spatial working memory and on parameters of oxidative stress in the prefrontal cortex, hippocampus, and striatum. First, 18 well-trained rats in 8-arm radial maze (8-RM) procedures received acute intracerebroventricular (icv) administration of AEME at doses of 10, 32, or 100 µg or saline (SAL) in a counterbalanced order and were tested 5 min later in 1-h delayed tasks in the 8-RM. Secondly, separated animals received acute icv administration of AEME at doses of 10 (n = 5), 32 (n = 5), or 100 µg (n = 5) or SAL (n = 5) for analysis of advanced oxidation protein products, thiobarbituric acid, catalase, glutathione peroxidase, and superoxide dismutase. A higher number of errors were seen in the 1-h post-delay performance after AEME 32 µg and AEME 100 µg when compared to SAL. In the striatum, animals receiving AEME 100 µg icv showed increased advanced oxidation protein products levels when compared to 10 µg, and also showed increased activity of glutathione peroxidase enzyme when compared to SAL but also comparing to AEME 32 µg and AEME 10 µg. These results showed that AEME impairs long-term spatial working memory and also induces greater protein oxidation and increased levels of antioxidant enzymes in the striatum.

Epidural direct current stimulation over the left medial prefrontal cortex facilitates spatial working memory performance in rats.

BACKGROUND: Extensive evidence supports the notion that modulation of PFC excitability using low-intensity electrical stimulation is a promising modality for treating neuropsychiatric diseases and improving cognitive function. OBJECTIVE: This study examined the effects of epidural direct current stimulation (eDCS), a method providing smaller shunting of current and more focal stimulation, on spatial working memory. METHODS: Male Wistar rats that were well trained in an 8-arm radial maze and in which 5-mm round electrodes were implanted over the left medial prefrontal cortex (mPFC) received anodal eDCS (400 µA during 11 min) (n = 9) or sham procedure (n = 9) five minutes before delayed tests in the radial maze. RESULTS: Animals that received eDCS over the left mPFC had significantly fewer errors in the post-delay performance on the 1-h (P < 0.01), 4-h (P < 0.001), and 10-h (P < 0.001) delayed tests compared with sham-treated animals. General locomotor activity was unaffected because time spent in each visited arm did not change significantly by eDCS. There was no evidence of neuronal lesions in the mPFC underneath the eDCS. CONCLUSIONS: Our results suggest that epidural direct current stimulation over the mPFC facilitates spatial working memory in rats, an effect that persisted over the long term.