One factor that contributes to the development and maintenance of nicotine addiction is the ability of nicotine to produce long-lasting modifications of behavior, yet little is known about Repotrectinib cost the mechanisms by

which nicotine alters the underlying synaptic plasticity responsible for behavioral changes. This study is the first to explore how nicotine interacts with learning to alter gene transcription, which is a process necessary for long-term memory consolidation. Transcriptional upregulation of hippocampal jun-N terminal kinase 1 (JNK1) mRNA was found in mice that learned contextual fear conditioning (FC) in the presence of nicotine, whereas neither learning alone nor nicotine administration alone exerted an effect. Furthermore, the upregulation of JNK1 was absent in beta 2 nicotinic receptor subunit knockout Daporinad ic50 mice, which are mice that do not show enhanced learning by nicotine. Finally, hippocampal JNK activation was increased in mice that were administered nicotine before conditioning, and the inhibition of JNK during consolidation prevented the nicotine-induced enhancement

of contextual FC. These data suggest that nicotine and learning interact to alter hippocampal JNK1 gene expression and related signaling processes, thus resulting in strengthened contextual memories. Neuropsychopharmacology (2010) 35, 483-492; doi: 10.1038/npp.2009.153; published online 23 September 2009″
“Chronic drug use may lead to sufficient drug intake to produce dependence and the emergence of abstinence signs during ASP2215 withdrawal. Although withdrawal can increase the reinforcing effects of some drugs (eg opioids), the impact of withdrawal on the reinforcing effects of stimulants like cocaine is less clear. This study used a novel cocaine vs food choice procedure to examine the relative reinforcing strength

of cocaine before, during, and after exposure to graded levels of extended cocaine access. Responding in four rhesus monkeys was maintained by cocaine (0-0.1 mg/kg/injection) and food delivery under a concurrent-choice schedule during daily 2-h sessions. Under baseline conditions, cocaine maintained a dose-dependent increase in cocaine choice. Subsequently, subjects were exposed to and withdrawn from periods of extended cocaine access, which was accomplished by implementing daily 21-h supplemental sessions of cocaine self-administration in addition to daily choice sessions. During supplemental sessions, cocaine (0.1 mg/kg/injection) was available under a fixed-ratio 10/time-out X schedule, and the duration of the time-out was varied from 30 to 7.5 min. Cocaine intake increased 10-fold to >11 mg/kg/day during exposure to supplemental sessions with the shortest post-injection time-out. However, parameters of cocaine choice were not significantly affected either during or after extended cocaine access.