Long-term (trophic) purinergic signalling: purinoceptors control cell proliferation, differentiation and death

The purinergic signalling system, which uses purines and pyrimidines as chemical transmitters, and purinoceptors as effectors, is deeply rooted in evolution and development and is a pivotal factor in cell communication. The ATP and its derivatives function as a 'danger signal' in the most primitive forms of life. Purinoceptors are extraordinarily widely distributed in all cell types and tissues and they are involved in the regulation of an even more extraordinary number of biological processes. In addition to fast purinergic signalling in neurotransmission, neuromodulation and secretion, there is long-term (trophic) purinergic signalling involving cell proliferation, differentiation, motility and death in the development and regeneration of most systems of the body. In this article, we focus on the latter in the immune/defence system, in stratified epithelia in visceral organs and skin, embryological development, bone formation and resorption, as well as in cancer. Cell Death and Disease (2010) 1, e9; doi:10.1038/cddis.2009.11; published online 14 January 201

Low ethanol sensitivity and increased ethanol consumption in mice lacking adenosine A2A receptors.

We have shown previously that the severity of handling-induced convulsions during ethanol withdrawal was reduced in A2A receptor knock-out (A2AR-/-) mice. In the present report, we further characterize the role of adenosine A(2A) receptors in ethanol consumption and neurobiological responses to this drug of abuse. Male A2AR-/- mice showed increased consumption of solutions containing 6 and 20% (v/v) ethanol compared with wild-type (A2AR+/+) control mice; female A2AR-/- mice showed increased consumption of solutions containing 6 and 10% ethanol. This slightly higher ethanol consumption was also related to increased ethanol preference. In contrast, A2AR-/- mice showed normal consumption of solutions containing either sucrose or quinine. Relative to A2AR+/+ mice, A2AR-/- mice were found to be less sensitive to the sedative effect of 3.0 gm/kg ethanol, as measured by more rapid recovery from ethanol-induced loss of righting reflex, and to the hypothermic effects of 1.5, 3.0, and 4.0 gm/kg ethanol, although plasma ethanol levels did not differ significantly between the two genotypes. The selective adenosine A2A receptor antagonist ZM 241385 (4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol) (10-30 mg/kg) significantly attenuated ethanol-induced (4.0 gm/kg) hypothermia in CD1 mice. To assess whether ethanol administration would induce differential tolerance in A2AR-/- and wild-type mice, we administered ethanol (3.0 gm/kg) over 4 consecutive days and found no difference in the development of tolerance; however, female A2AR-/- mice showed a lower tolerance-acquisition rate. These data suggest that activating the A2A receptors may play a role in suppressing alcohol-drinking behavior and is associated with the sensitivity to the intoxicating effects of acute ethanol administration.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Frequency of anxious and depressive symptoms in a population of cannabidiol users

33rd Congress of the European-College-of-Neuropsychopharmacology (ECNP), ELECTR NETWORK, SEP 12-15, 2020International audienc

Decreased alcohol self-administration and increased alcohol sensitivity and withdrawal in CB1 receptor knockout mice.

Recent advances in the understanding of the neurobiological basis of alcohol dependence suggest that the endocannabinoid system may play a key role in the reinforcing effects of ethanol. In the present study, disruption of CB1 receptors in mice generated on a CD1 background decreased both ethanol consumption and preference. This decreased ethanol self-administration was associated with increased sensitivity to the acute intoxicating effects of ethanol. Mutant mice were more sensitive to the hypothermic and sedative/hypnotic effects of acute ethanol administration (1.5-4.0 g/kg), although plasma ethanol concentrations did not differ from those of controls. Moreover, wild-type mice exhibited normal locomotor activation caused by 1.0-2.5 g/kg injection of ethanol, whereas mutant mice displayed sedation in response to the injection of the same ethanol doses. The severity of alcohol withdrawal-induced convulsions was also increased in CB1(-/-) mice. Our results suggest that CB1 receptors participate in the regulation of ethanol drinking and demonstrate that their disruption lead to increased ethanol sensitivity and withdrawal severity.Comparative StudyJournal Articleinfo:eu-repo/semantics/publishe

Can board games reduce cognitive disorders in patients with alcohol dependence during detoxification?

32nd Congress of the European-College-of-Neuropsychopharmacology (ECNP), Copenhagen, DENMARK, SEP 07-10, 2019International audienc

Alcohol use increase in polysubstance users during quarantine related to SARS-Cov2 infection-19

International audienc

EFFECT OF N-ACETYLCYSTEINE ON MOTIVATION, SEEKING AND RELAPSE TO ETHANOL SELFADMINISTRATION IN ALCOHOL DEPENDENT AND NONDEPENDENT RATS

International audienc

EFFICACY OF HDAC1 INHIBITORS IN A NEW RAT MODEL OF BINGE DRINKING

39th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA), New Orleans, LA, JUN 25-29, 2016International audienc

EFFECT OF N-ACETYLCYSTEINE ON MOTIVATION, SEEKING AND RELAPSE TO ETHANOL SELFADMINISTRATION IN ALCOHOL DEPENDENT AND NONDEPENDENT RATS

International audienc