Inhibition of Protein kinase Mzeta (PKMζ) in the mesolimbic system alters cocaine sensitization in rats.

Chronic cocaine use produces long-lasting changes in reward circuits that may underlie the transition from casual to compulsive patterns of drug use. Although strong neuroadaptations within the mesocorticolimbic system are known to occur, the specific role of these drug-induced plasticities on sensitization remains to be elucidated. Here we investigate whether PKMζ, a protein involved in maintaining long-term potentiation (LTP), plays a role in these cocaine-induced changes in synaptic strengthening. We performed whole-cell voltage clamp recordings of putative ventral tegmental area (VTA) dopamine (DA) cells 24 hours after five days of 15 mg/kg i.p. cocaine or isovolumetric saline injections. We observed that superfusion of 5µM ZIP (PKMζ inhibitory peptide) decreased AMPA currents and AMPA/NMDA ratios only in cocaine sensitized rats. In vivo ZIP microinfusions (10 nmol) into the VTA after cocaine sensitization decreased locomotor activity on a subsequent cocaine challenge only if given ZIP is given before the withdrawal period. On the other hand, ZIP microinfusions into the nucleus accumbens (NAc) core after a seven days withdrawal period disrupt the expression of locomotor sensitization. The present data provide a potentially relevant region, and time-specific PKMζ-dependent brain mechanism that enables sensitization. Our results support the vision that addiction involves a pathological learning process. They imply that if this synaptic strengthening is reversed, changes in the behavioral response may also be overturned.

Descriptive profile of surgically-confirmed adult central nervous system tumors in Puerto Rico.

INTRODUCTION: Published studies regarding the incidence of central nervous system (CNS) tumors in Puerto Rico (PR) are exceedingly rare. The general understanding is that the incidence of these tumors in Puerto Rico is similar to the one found in the United States of America (USA). The objective of this study is to describe the specific profile of all the CNS tumors that are surgically intervened in Puerto Rico, through the creation of a database. METHODS: A retrospective analysis of all the surgical procedures from January 1, 2002 to May 31, 2006 for adult CNS tumors in Puerto Rico was performed. Each case was evaluated for demographic information, operative procedure, lesion description and official pathological report. Recurrent lesions were excluded. The information was organized to form a database of all the CNS neoplasms. RESULTS: A total of 1,018 procedures for CNS tumors were performed on 1,005 patients. The incidence rate of surgically intervened CNS tumors in Puerto Rico is 6 per 100,000 people. CNS tumors were more common in women than in men (58% vs. 42%), respectively. The mean age was 52.4 years. The most common histological type found was meningioma WHO I (24%), followed by pituitary adenomas (16%), and glioblastoma multiforme (14%). CONCLUSIONS: Our results reflect a unique histopathological distribution of operated CNS tumors in Puerto Rico. In this series, primary tumors are more common than metastatic tumors. Benign histological tumors were more frequent than more malignant variants. Although this study reflects only the histologically diagnosed tumors, it is headway towards diagnosing the incidence of all CNS tumors in Puerto Rico.