It has been suggested that endocannabinoid mechanisms are involved in the control of ethanol consumption.
The aims of the present study were (1) to evaluate the role of the endocannabinoid system in ...the control of operant ethanol self-administration and in the reinstatement of ethanol seeking, when induced by stress or conditioned stimuli and (2) to offer new insights on the specificity of such a role.
Rats were administered intraperitoneally with the selective cannabinoid CB1 receptor antagonist, SR-141716A, 30 min before operant self-administration or reinstatement sessions. Two schedules of reinforcement, the fixed-ratio 1 (FR1) and the progressive ratio (PR), were used to study 10% (w/v) alcohol and 5.0% sucrose self-administration. NaCl (2% w/v) intake in sodium-depleted rats was studied only under the FR1 program.
Treatment with SR-141716A (0.3-3.0 mg/kg) significantly attenuated FR1 alcohol self-administration and lowered the break point for ethanol under PR. SR-141716A also markedly inhibited the reinstatement of alcohol seeking elicited by presentation of cues predictive of drug availability. Conversely, the cannabinoid antagonist did not prevent the reinstatement of alcohol seeking induced by foot-shock stress. Lever pressing for sucrose under FR1 and PR schedules was also significantly decreased by SR-141716A treatment, whereas the drug modestly and only at the highest dose decreased 2% NaCl self-administration.
Results emphasize that endocannabinoid mechanisms play a major role in the control of ethanol self-administration and in the reinstatement of conditioned ethanol seeking. However, these effects extend to the control of operant behaviours motivated by natural rewards (i.e. sucrose). On the other hand, SR-141716A only weakly reduces NaCl self-administration in sodium-depleted rats, in which salt intake is largely controlled by homeostatic mechanisms. Overall, these observations demonstrate that the inhibition of operant behaviour following blockade of CB1 receptors by SR-141716A is linked to a reduction of reward-related responding and is not related to drug-induced motor deficits.
The present study of human alcoholics aims to evaluate DNA methylation patterns in the prodynorphin gene (PDYN) promoter and to identify single nucleotide polymorphisms (SNPs) that are associated ...with alcohol dependence and with altered DNA methylation. Genomic DNA was isolated from peripheral blood cells of alcoholics and healthy controls, and...
The present study examined the effect of two A(2A) adenosine receptor (AR) agonists, CGS 21680 and VT 7, on high-palatability food (HPF) intake in a model of binge eating in sated rats and on ...low-palatability food (LPF) intake in food-deprived rats. Binge eating was induced in female rats by three 8-day cycles of food restriction/refeeding, followed by acute stress. Two groups of rats were used: NR+NS rats normally fed and not stressed and R+S rats exposed to cycles of food restriction/refeeding and then stressed. R+S rats had higher intake of HPF than the NR+NS controls. The two A(2A)AR agonists were tested at doses of 0.1 and 0.05 mg/kg intraperitoneally; VT 7 did not modify locomotor activity at either dose, whereas CGS 21680 only slightly reduced it at the higher dose tested. The injection of 0.1 mg/kg of both agonists markedly reduced HPF intake both in R+S and in NR+NS rats. The dose of 0.05 mg/kg was inactive. CGS 21680 and VT 7, 0.1 mg/kg, also reduced the standard LPF intake in 24 h food-deprived rats; however, they did not reduce water intake, indicating that their effect on food intake is selective. The dose of 0.05 mg/kg was inactive. Thus, A(2A)AR agonists exert a rather general effect on food intake, inhibiting both HPF intake in sated rats and LPF intake in food-deprived rats. They may potentially be useful pharmacological agents to control binge-related eating disorders and to reduce food overconsumption associated with obesity.
Amphotericin B is a polyene macrolide derived from Streptomyces nodosus. Introduced into therapy in 1957, for decades amphotericin B has been the "gold standard" for fighting systemic fungal ...infections. In order to facilitate its systemic use, much attention has been paid to the development of pharmaceutical forms that could reduce its toxicity, especially for the kidney. Because of its low solubility in water and excellent solubility in lipids, amphotericin B is an ideal candidate for lipid-based formulations. Three different lipid formulations for intravenous infusion are currently commercially available: liposomal amphotericin (AmBisome), Amphotericin lipid complex (Abelcet) and Amphotericin colloidal dispersion (Amphocil). The three lipid formulations of amphotericin B show significantly different structural, physical, chemical, pharmacokinetic, pharmacodynamic and toxicological characteristics. Several lines of evidence indicate that the three formulations of amphotericin B are not therapeutically equivalent. First, they are not bioequivalent. Second, even though a complete picture of controlled clinical research designed to compare effectiveness and safety of the three lipid formulations is not available, all the clinical studies analyzed report clear differences in toxicity between the three formulations. AmBisome appears to be clearly less toxic than the other two formulations, in terms of nephrotoxicity and of incidence of infusion-related adverse events. Third, the therapeutic non-equivalence of the three lipid formulations of amphotericin B is further supported by statements of Conferences and Scientific Societies that in their recommendations have awarded different grading to the three lipid formulations. (www.actabiomedica.it).
Nociceptin/orphanin FQ (N/OFQ) controls several biological functions via selective activation of the N/OFQ peptide receptor (NOP). (pF)Phe4Aib7Arg14Lys15N/OFQ‐NH2 (UFP‐112) is an NOP receptor ligand ...designed using a combination of several chemical modifications in the same peptide sequence that increase NOP receptor affinity/potency and/or reduce susceptibility to enzymatic degradation. In the present review article, we summarize data from the literature and present original findings on the in vitro and in vivo pharmacological features of UFP‐112. Moreover, important biological actions and possible therapeutic indications of NOP receptor agonists are discussed based on the results obtained with UFP‐112 and compared with other peptide and nonpeptide NOP receptor ligands.
PDF