Maria Rosana Ramirez

Mice Deficient for the Vesicular Acetylcholine Transporter Are Myasthenic and Have Deficits in Object and Social Recognition

An important step for cholinergic transmission involves the vesicular storage of acetylcholine (ACh), a process mediated by the vesicular acetylcholine transporter (VAChT). In order to understand the physiological roles of the VAChT, we developed a genetically altered strain of mice with reduced expression of this transporter. Heterozygous and homozygous VAChT knockdown mice have a 45% and 65% decrease in VAChT protein expression, respectively. VAChT deficiency alters synaptic vesicle filling and affects ACh release. Whereas VAChT homozygous mutant mice demonstrate major neuromuscular deficits, VAChT heterozygous mice appear normal in that respect and could be used for analysis of central cholinergic function. Behavioral analyses revealed that aversive learning and memory are not altered in mutant mice; however, performance in cognitive tasks involving object and social recognition is severely impaired. These observations suggest a critical role of VAChT in the regulation of ACh release and physiological functions in the peripheral and central nervous system.

Modulation of working, short- and long-term memory by nicotinic receptors in the basolateral amygdala in rats.

Male Wistar rats were exposed to one-trial step-down inhibitory avoidance training using a 0.5 mA footshock. Through bilaterally implanted indwelling cannulae, they received bilateral 0.5 microL infusions of saline, mecamylamine (1.0 or 10.0 microg/side), or nicotine (0.6 or 3.0 microg/side) into the basolateral complex of the amygdaloid nucleus (BLA). Infusions were either 10 min before training (Experiment 1) or 4 min after training (Experiment 2). In Experiment 1, the animals were tested three times: first for working memory (WM) 5 s after training, then for short-term memory (STM) 90 min later, and finally for long-term memory (LTM) 24 h later. Mecamylamine depressed and nicotine enhanced WM, STM, and LTM. In Experiment 2, the treatments were given after WM was presumably over. Again, mecamylamine inhibited and nicotine enhanced STM and LTM. The results indicate that nAChRs in BLA participate in the regulation of WM formation and STM and LTM acquisition and consolidation.

Preliminary studies on the antinociceptive activity of Vaccinium ashei berry in experimental animal models.

The aim of this study was to carry out pharmacological screening in order to evaluate the potential effects of lyophilized fruits of different cultivars of Vaccinium ashei Reade (Family Ericaceae) berries, commonly known as rabbiteye blueberries, on nociception. This was achieved using the formalin, hot plate, tail-flick, and writhing tests in mice. During this experiment the mice consumed approximately 3.2-6.4 mg/kg/day (p.o.) of the anthocyanins. The extract was administered for 21 days or 60 minutes before test. Morphine and diclofenac (10 mg/kg, p.o.) as the standard drug (positive control) and water (via oral gavage) as the negative control were administered before all tests. The blueberry extract produced a significant decrease in constrictions induced by acetic acid and caused graded inhibition of the second phase of formalin-induced pain. Moreover, in both the hot plate and tail-flick tests, it significantly increased the threshold. These data suggest that the extract from V. ashei produced antinociceptive effects, as demonstrated in the experimental models of nociception in mice. Additional experiments are necessary in order to clarify the true target for the antinociceptive effects of rabbiteye blueberry extract.

Effects of an Acute Treatment with L-Thyroxine on Memory, Habituation, Danger Avoidance, and on Na+, K+-ATPase activity in Rat Brain

Thyroid hormones (THs) have a relevant action on brain development and maintenance. By using an acute treatment to induce a hyperthyroid animal model, we aimed at investigating the effect of an altered THs levels on learning and memory and on the activity of Na(+), K(+)-ATPase in the rat brain. Our results have shown that the acute treatment with L-T4 did not alter the retrieval of the inhibitory avoidance task, but had a significant effect on the elevated plus maze and on open-field performance in rats. We suggest that animals subjected to L-T4 administration improved the habituation to a novel environment as well as a better evaluation of a dangerous environment, respectively. Na(+), K(+)-ATPase activity is increased in parietal cortex (30%), but it is not altered in hippocampus in L-T4 treated group. These both brain structures are involved in memory processing and it was previously demonstrated that there is a double dissociation between them for spatial location information, perceptual and episodic memory. We propose the hypothesis that this increase of Na(+), K(+)-ATPase activity in parietal cortex may be correlated to our results in behavior tests, which suggest a role of THs as well as of the Na(+), K(+)-ATPase in the cognitive process.