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The triorganotin compound trimethyltin (TMT) is a highly toxic molecule which has a great impact on human health. The aim of this study was to investigate the specific alteration of dopamine receptors and transporters in the hippocampus of TMT-treated rats. The TMT-treated group showed impaired spatial reference memory in a Morris water maze task compared to the control group, whereas memory consolidation tested 24 hours after the last training session was preserved. In the open field, TMT-treated rats showed a decrease in time spent in rearing episodes reflecting a lower interest to explore a novel environment. In the hippocampal area of the TMT-treated group, we observed a reduction in neuronal viability accompanied by a significant decrease in the expression of the dopamine receptors (D1 and D2), and dopamine transporters (DAT, VMAT1 and VMAT2). A less pronounced reduction was observed for D3 and D5 while D4 did not change. These data were confirmed by RT-PCR analysis. The present study on TMT-induced neurodegeneration highlights the link between hippocampal asset of dopamine receptors and transporters and the impaired performance of rats in a spatial reference memory task.

Both oxidative stress and inflammation are elevated in brains of Alzheimer's disease patients, but their pathogenic significance still remains unclear. Current evidence support the hypothesis that non-steroidal anti-inflammatory drugs (NSAIDs) and antioxidant therapy might protect against the development of Alzheimer's disease, and ibuprofen has the strongest epidemiological support. In the present work our attention was focused on (R)-a-lipoic acid considered as a potential neuroprotective agent in Alzheimer's disease therapy. In particular, we investigated a new co-drug (1) obtained by joining (R)-a-lipoic acid and ibuprofen via a diamide bond, for evaluating its potential to antagonize the deleterious structural and cognitive effects of p-amyloid (1-40) in an infused Alzheimer's disease rat model. Our results indicated that infusion of p-amyloid (1-40) impairs memory performance through a progressive cognitive deterioration; however, ibuprofen and co-drug 1 seemed to protect against behavioural detriment induced by simultaneous administration of p-amyloid (1-40) protein.The obtained data were supported by the histochemical findings of the present study: p-amyloid protein was less expressed in 1-treated than in ibuprofen and (R)-a-lipoic acid alone-treated cerebral cortex. Taken together, the present findings suggest that co-drug 1 treatment may protect against the cognitive dysfunction induced by intracerebroventricular infusion of p-amyloid (1-40) in rats. Thus, co-drug 1 could prove useful as a tool for controlling Alzheimer's disease-induced cerebral amyloid deposits and behavioural deterioration.Alzheimer's disease is an age-dependent neurodegenerative disorder that gradually destroys patient memory and cognition in the geriatric population for which there is no effective treatment at present (1-2). The disease is characterised pathologically by senile cerebral plaques constituted chiefly by extracellular deposition of~-amyloid peptide in hippocampal and cerebral cortical regions accompanied by the presence ofthread-like neuronal structures that occupy much of the cytoplasm of pyramidal neurons; these neurofibrillary tangles are aggregates of hyperphosphorilated microtubular Tau

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IV in three gerbils. 123I-FP CIT was used in five gerbils to investigate dopamine transporters (DAT). 99mTc-ECD perfusion scan was performed in four gerbils for anatomical identification. Results. Image quality of the 5-HT2A receptor radioligand studies improved substantially after P-gp inhibition with cyclosporine. Specific binding to the 5-HT2A receptors and DAT sites was observed by the regional distribution of the radioactivity in the brain which correlated well with the known presence of 5-HT2A receptors and DAT sites (cortical areas and basal ganglia) versus low uptake in the cerebellum. Using the HiSPECT system, tomographic images of 1.4 mm resolution can be obtained. Conclusion. These results indicate that the use of HiSPECT in Mongolian gerbils is feasible and that the aforementioned biological markers can be used to investigate the biological base of stereotypies in gerbils.

Ibuprofen and Lipoic Acid Diamides as Potential Codrugs with NeuroprotectiveActivity. -Conjugates (I) are synthesized and evaluated for their physicochemical and antioxidant properties. These new compounds are extremely stable in aqueous buffer solution (pH = 1.3 and 7.4) and show a slow bioconversion to ibuprofen and (R)-α-lipoic acid in rat and human plasma. Moreover, they show in vitro free-radical scavenging activity. -(SOZIO, P.; D'AURIZIO, E.; IANNITELLI, A.; CATALDI, A.; ZARA, S.; CANTALAMESSA, F.; NASUTI, C.; DI STEFANO*, A.; Arch. Pharm.

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