Endocannabinoid Regulation of Acute and Protracted Nicotine Withdrawal: Effect of FAAH Inhibition

Evidence shows that the endocannabinoid system modulates the addictive properties of nicotine. In the present study, we hypothesized that spontaneous withdrawal resulting from removal of chronically implanted transdermal nicotine patches is regulated by the endocannabinoid system. A 7-day nicotine dependence procedure (5.2 mg/rat/day) elicited occurrence of reliable nicotine abstinence symptoms in Wistar rats. Somatic and affective withdrawal signs were observed at 16 and 34 hours following removal of nicotine patches, respectively. Further behavioral manifestations including decrease in locomotor activity and increased weight gain also occurred during withdrawal. Expression of spontaneous nicotine withdrawal was accompanied by fluctuation in levels of the endocannabinoid anandamide (AEA) in several brain structures including the amygdala, the hippocampus, the hypothalamus and the prefrontal cortex. Conversely, levels of 2-arachidonoyl-sn-glycerol were not significantly altered. Pharmacological inhibition of fatty acid amide hydrolase (FAAH), the enzyme responsible for the intracellular degradation of AEA, by URB597 (0.1 and 0.3 mg/kg, i.p.), reduced withdrawal-induced anxiety as assessed by the elevated plus maze test and the shock-probe defensive burying paradigm, but did not prevent the occurrence of somatic signs. Together, the results indicate that pharmacological strategies aimed at enhancing endocannabinoid signaling may offer therapeutic advantages to treat the negative affective state produced by nicotine withdrawal, which is critical for the maintenance of tobacco use

The effects of acute, chronic, and withdrawal from chronic nicotine on novel and spatial object recognition in male C57BL/6J mice

Rationale: Spatial and novel object recognition learning is different from learning that uses aversive or appetitive stimuli to shape acquisition because no overt contingencies are needed. While this type of learning occurs on a daily basis, little is known about how nicotine administration affects it.Objectives: To determine the effects of acute, chronic, and withdrawal from chronic nicotine on two related but distinct incidental learning tasks, novel and spatial object recognition.Methods: In C57BL/6J mice, the effects of acute (0.045-0.18 mg/kg), chronic (6.3 mg/kg/day), and withdrawal from chronic nicotine on novel and spatial object recognition were examined.Results: With a 48-h delay between training and testing, acute nicotine enhanced spatial (difference score, saline?=?3.34 s, nicotine?=?7.71 s, p?=?0.029) but resulted in a deficit in novel object recognition (difference score, saline?=?8.76 s, nicotine?=?4.48 s, p?=?0.033). Chronic nicotine resulted in a strong trend towards a deficit in spatial object recognition (difference score, saline?=?4.01 s, nicotine?=?1.81 s, p?=?0.059) but had no effect on novel object recognition, and withdrawal from chronic nicotine disrupted spatial object recognition (difference score, saline?=?3.00 s, nicotine?=?0.17 s, p?=?0.004) but had no effect on novel object recognition.Conclusions: The effects of nicotine on spatial object recognition shift from enhancement to deficit as administration changes from acute to chronic and withdrawal. These effects were specific for spatial object recognition, which may be due to differing underlying neural substrates involved in these tasks. Understanding how nicotine alters learning has implications for understanding diseases associated with altered cholinergic function<br/

Lack of correlation between the activity of the mesolimbic dopaminergic system and the rewarding properties of pregabalin in mouse

International audiencePregabalin is a psychoactive drug indicated in the treatment of epilepsy, neuropathic pain, and generalized anxiety disorders. Pregabalin acts on different neurotransmission systems by inactivating the alpha2-delta subunit of voltage-gated calcium channels. In light of this pharmacological property, the hypothesis has been raised that pregabalin may regulate the mesolimbic dopamine pathway and thereby display a potential for misuse or abuse as recently observed in humans. Although some preclinical data support this possibility, the rewarding properties of gabapentinoid are still a matter for debate

Methods of Analysis and Meta-Analysis for Identifying Differentially Expressed Genes.

Microarray approaches are widely used high-throughput techniques to assess simultaneously the expression of thousands of genes under certain conditions and study the effects of certain treatments, diseases, and developmental stages. The traditional way to perform such experiments is to design oligonucleotide hybridization probes that correspond to specific genes and then measure the expression of the genes in order to determine which of them are up-or down-regulated compared to a condition that is used as a control. Hitherto, individual experiments cannot capture the bigger picture of how a biological system works and, therefore, data integration from multiple experimental studies and external data repositories is necessary to understand the function of genes and their expression patterns under certain conditions. Therefore, the development of methods for handling, integrating, comparing, interpreting and visualizing microarray data is necessary. The selection of an appropriate method for analysing microarray datasets is not an easy task. In this chapter, we provide an overview of the various methods developed for microarray data analysis, as well as suggestions for choosing the appropriate method for microarray meta-analysis

Urban research and complexity

International audienc