Involvement of nNOS/NO/sGC/cGMP signaling pathway in cocaine sensitization and in the associated hippocampal alterations: does phosphodiesterase 5 inhibition help to drug vulnerability?

RATIONALE: Repeated cocaine administration induces behavioral sensitization in about 50 % of treated animals. Nitric oxide could be involved in the acquisition and maintenance of behavioral cocaine effects, probably by activation of neuronal nitric oxide synthase (nNOS)/NO/soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP) signaling pathway, since inhibition of the nNOS enzyme attenuates development of sensitization in rats. On the other hand, increased cGMP availability by phosphodiesterase 5 inhibitors has been correlated to the misuse and recreational use of these agents and also to the concomitant use with illicit drugs in humans. Hippocampus is an important brain region for conditioning to general context previously associated to drug availability, influencing drug-seeking behavior and sensitization. Moreover, cocaine and other drugs of abuse can affect the strength of glutamate synapses in this structure, lastly modifying neuronal activity in main regions of the reward circuitry. OBJECTIVE: The objective of this study is to determine whether the pharmacological manipulation of nNOS/NO/sGC/cGMP signaling pathway altered changes induced by repeated cocaine exposure. RESULTS: The present investigation showed a relationship between behavioral cocaine sensitization, reduced threshold to generate long-term potentiation (LTP) in hippocampal dentate gyrus, and increased nNOS activity in this structure. However, when nNOS or sGC were inhibited, the number of sensitized animals was reduced, and the threshold to generate LTP was increased. The opposite occurred when cGMP availability was increased. CONCLUSION: We demonstrate a key role of the nNOS activity and NO/sGC/cGMP signaling pathway in the development of cocaine sensitization and in the associated enhancement of hippocampal synaptic transmission.

Impact of contextual cues in the expression of the memory associated with diazepam withdrawal: involvement of hippocampal PKMζ in vivo, and Arc expression and LTP in vitro.

Hippocampal synaptic plasticity has been related to learning and adaptive processes developed during chronic drug administration, suggesting the existence of a common neurobiological mechanism mediating drug addiction and memory. Moreover, protein kinase M zeta (PKMζ) is critical for the maintenance of hippocampal long-term potentiation (LTP) and spatial conditioned long-term memories. Also, a link between activity-regulated cytoskeleton-associated protein (Arc), PKMζ and LTP has been proposed. Our previous results demonstrated that re-exposure to the withdrawal environment was able to evoke the memory acquired when the anxiety measured as a diazepam (DZ) withdrawal sign was experienced. In the present work we evaluated if the memory associated with DZ withdrawal could be affected by changes in the contextual cues presented during withdrawal and by intrahippocampal administration of a PKMζ inhibitor. We found that the context was relevant for the expression of withdrawal signs as changes in contextual cues prevented the expression of the anxiety-like behavior observed during plus-maze (PM) re-exposure, the associated enhanced synaptic plasticity and the increase in Arc expression. Furthermore, intrahippocampal administration of PKMζ inhibitor previous to re-exposure to the PM test also impaired expression of anxiety-like behavior and the facilitated LTP. These results support the relevance of the hippocampal synaptic plasticity in the maintenance of the memory trace during benzodiazepines withdrawal, adding new evidences for common mechanisms between memory and drug addiction that can be intervened for treatment or prevention of this pathology.

Changes in hippocampal arc protein expression and synaptic plasticity by the presentation of contextual cues linked to drug experience.

Contextual cues linked to drug experience have been frequently associated to craving and relapse, with this phenomenon being described in human and experimental animals. Hippocampal synaptic plasticity has been related to learning, memory, and adaptive processes developed during chronic administration of drug abuse. In this study, we investigated if the environmental context associated with withdrawal experience was able to evoke the same behavioral alteration observed after chronic benzodiazepine administration. Furthermore, we studied the hippocampal synaptic plasticity and anatomical expression of Arc protein during withdrawal and the re-exposure to the context associated with anxiety expression (characteristic sign of benzodiazepines withdrawal). It was demonstrated that re-exposure evoked on days 15 and 25 after the first exposure the same behavior. An increased hippocampal synaptic plasticity, expressed as a lower threshold to induce long-term potentiation on dentate gyrus, was observed in animals dependent on diazepam and during retrieval, in the same group, until day 15. This plastic change disappeared 25 days after the first exposure. An overexpression of Arc protein in the dorsal dentate gyrus and CA1 on the first day of withdrawal in the dependent animals was observed.

Análisis de expectativas y sentimientos de familias de niños y niñas de 0 a 6 años con discapacidad en Paraguay / Analysis of expectations and feelings of families of children of 0 to 6 years with incapacity in Paraguay

El estudio de investigación es transeccional, descriptivo, a partir de un marco referencial que propone etapas o periodos, en el que se agrupan los sentimientos de familias con niños/as con discapacidades. Analiza las emociones familiares respecto al nacimiento de niños /as con discapacidades, entre 0 a 6 años. Se realizaron entrevistas mixtas a familias de 11 localidades de comunidades rurales y urbanas del país. Los resultados de la investigación muestran que las familias se encuentran situadas en diferentes etapas, con diferencias entre las zonas rurales y urbanas. En todas la localidades es mayor el número de familias que ven a sus niños y niñas con discapacidad, como sujetos de derecho mas que como objetos de derecho.

Lesiones endoperiodontales / Endodontic-periodontal lesions

Como no podemos dividir al diente en una parte periodontal y otra endodóntica, es importante conocer que la pulpa afecta al periodonto por su extensión a furcación, sea esta a través de perforaciones accidentales o bien cuando los dientes sufren traumatismos, con conductos laterales y apicales capaz de concetarlos. De igual forma lo hacen las bolsas periodontales profundas o el trauma, ambas actúan separadas o coexisten en un sólo diente. Es importante saber diagnosticar; para ello se deben utilizar distintos elementos: clínicos o radiográficos adecuadamente al caso. Siempre realizando el tratamiento endodóntico inicial seguido de la terapia periodontal

Lesiones endoperiodontales / Endodontic-periodontal lesions

Como no podemos dividir al diente en una parte periodontal y otra endodóntica, es importante conocer que la pulpa afecta al periodonto por su extensión a furcación, sea esta a través de perforaciones accidentales o bien cuando los dientes sufren traumatismos, con conductos laterales y apicales capaz de concetarlos. De igual forma lo hacen las bolsas periodontales profundas o el trauma, ambas actúan separadas o coexisten en un sólo diente. Es importante saber diagnosticar; para ello se deben utilizar distintos elementos: clínicos o radiográficos adecuadamente al caso. Siempre realizando el tratamiento endodóntico inicial seguido de la terapia periodontal (AU)