Blockade of ERK Phosphorylation in the Nucleus Accumbens Inhibits the Expression of Cocaine-induced Behavioral Sensitization in Rats

Repeated administration of psychostimulants such as cocaine leads to the development of behavioral sensitization. Extracellular signal-Regulated Kinase (ERK), an enzyme important for long-term neuronal plasticity, has been implicated in such effects of these drugs. Although the nucleus accumbens (NAcc) is the site mediating the expression of behavioral sensitization by drugs of abuse, the precise role of ERK activation in this site has not been determined. In this study we demonstrate that blockade of ERK phosphorylation in the NAcc by a single bilateral microinjections of PD98059 (0.5 or 2.0micro g/side), or U0126 (0.1 or 1.0microg/side), into this site dose-dependently inhibited the expression of cocaine-induced behavioral sensitization when measured at day 7 following 6 consecutive daily cocaine injections (15 mg/kg, i.p.). Acute microinjection of either vehicle or PD98059 alone produced no different locomotor activity compared to saline control. Further, microinjection of PD98059 (2.0micro g/side) in the NAcc specifically lowered cocaine-induced increase of ERK phosphorylation levels in this site, while unaffecting p-38 protein levels. These results indicate that ERK activation in the NAcc is necessary for the expression of cocaine-induced behavioral sensitization, and further suggest that repeated cocaine evokes neuronal plasticity involving ERK pathway in this site leading to long-lasting behavioral changes.

A Clinical Analysis on Primary Cancer of the Gall Bladder / 대한소화기내시경학회지

Carcinoma of Gall bladder remains a terminal illness in most patients despite improved diagnostic capabilities, better perioperative care and a more aggresive surgical approch based on improved knowledge of this tumors natural histiory. Overall 5-year survival rates remain below 5%. This failure to significantly improve patient oucome is largely due to late recognition of gall badder cancer. Authors experienced 21 cases of gall bladder cancer confirmed by operation at the Kwang Ju Christian hospital from march 1983 to March 1991, and the results obtained were summarized as follows. (continue...)