17) but not for rs2026458, 1.03 (0.88-1.19). The OR for CAC was 1.22 (1.18-1.26) for rs9349379 and 1.28 (1.21-1.38) for rs12526453.
 
  Several PHACTR1 specifically rs9349379 and rs12526453 polymorphisms but not rs2026458, are associated with CAD. There are differences in the association of PHACTR1 SNPs with CAC. PHACTR1 warrants more attention and study for the prevention and treatment of CAD.
 Several PHACTR1 specifically rs9349379 and rs12526453 polymorphisms but not rs2026458, are associated with CAD. There are differences in the association of PHACTR1 SNPs with CAC. PHACTR1 warrants more attention and study for the prevention and treatment of CAD.Relapse is common amongst smokers attempting to quit and tobacco cue-induced craving is an important relapse mechanism. Preclinical studies commonly use cue-induced reinstatement of nicotine seeking to investigate relapse neurobiology. Previous research suggests dependence severity and nicotine intake history affect smoking resumption and cue-induced reinstatement of nicotine seeking. However, behavioural data may be interpreted in terms of nicotine reinforcement. This translational study investigated if individual differences in objectively assessed nicotine reinforcement strength were associated with cue-reactivity in both rats and human smokers, which to our knowledge has not been investigated before. Rats (n = 16) were trained to self-administer nicotine and were tested on a progressive ratio schedule of nicotine reinforcement, to assess reinforcer strength, and on a test of cue-induced reinstatement of nicotine seeking. Nicotine reinforcement strength was assessed in human smokers (n = 104) using a forced choice task (nicotine containing vs. denicotinised cigarettes) and self-reported cue-induced craving was assessed following exposure to smoking and neutral cues. Responding for nicotine under progressive ratio was strongly positively correlated with cue-induced reinstatement of nicotine seeking in rats. Nicotine choices in human smokers were significantly associated with cue-induced craving controlling for dependence severity, years of smoking, and urge to smoke following neutral cues. Findings suggest nicotine reinforcement strength is associated with both types of cue-induced behaviour, implying some translational commonality between cue-induced craving in human smokers and cue-induced reinstatement of nicotine seeking in rats. Findings are discussed in relation to clinical implications and whether these laboratory tasks assess drug 'wanting'.Use of alcohol (EtOH) and nicotine (Nic) typically begins during adolescence. Smoking and drinking often occur together and lead to a higher consumption of alcohol. Although we have shown that Nic+EtOH is reinforcing in self-administration tests in adolescent male rats, whether Nic+EtOH affects other behaviors or neuronal activity in an age-dependent manner is unknown. To address this, adolescent and adult male rats were given intravenous injections of Nic (30 µg/kg)+EtOH (4 mg/kg) and evaluated for locomotor and anxiety-like behaviors. Regional neuronal activity, assessed by cFos mRNA expression, was measured and used to evaluate functional connectivity in limbic regions associated with anxiety and motivation. Nic+EtOH increased locomotor activity and was anxiolytic in adolescents, but not adults. The posterior ventral tegmental area (pVTA), a critical regulator of drug reward, was selectively activated by Nic+EtOH in adults, while activity in its target region, the NAc-shell, was decreased. Drug-induced alterations in functional connectivity were more extensive in adults than adolescents and may act to inhibit behavioral responses to Nic+EtOH that are seen in adolescence. Overall, our findings suggest that brief, low-dose exposure to Nic+EtOH produces marked, age-dependent changes in brain and behavior and that there may be an ongoing maturation of the pVTA during adolescence that allows increased sensitivity to Nic+EtOH's reinforcing, hyperlocomotor, and anxiolytic effects. Furthermore, this work provides a potential mechanism for high rates of co-use of nicotine and alcohol by teenagers this drug combination is anxiolytic and recruits functional networks that are unique from protective, inhibitory networks recruited in the mature and adult brain.Drug combinations are being studied as potential therapies to increase the efficacy or improve the safety profile of weight loss medications. This study was designed to determine the anorectic interaction and safety profile of 5-hydroxytryptophan (5-HTP)/carbidopa + diethylpropion and 5-HTP/carbidopa + phentermine combinations in rats. The anorectic effect of individual drugs or in combination was evaluated by the sweetened milk test. Isobologram and interaction index were employed to determine the anorectic interaction between 5-HTP/carbidopa and diethylpropion or phentermine. Plasma serotonin (5-HT) was measured by ELISA. Safety of repeated doses of both combinations in rats was evaluated using the tail sphygmomanometer, cardiac ultrasound, hematic biometry and blood chemistry. A single oral 5-HTP, diethylpropion or phentermine dose increased the anorectic effect, in a dose-dependent fashion, in 12 h-fasted rats. A dose of carbidopa at 30 mg/kg reduced the 5-HTP-induced plasmatic serotonin concentration and augmented the 5-HTP-induced anorectic effect. Isobologram and interaction index indicated a potentiation interaction between 5-HTP/30 mg/kg carbidopa + diethylpropion and 5-HTP/30 mg/kg carbidopa + phentermine. Chronic administration of experimental ED40 of 5-HTP/30 mg/kg carbidopa + phentermine, but not 5-HTP/30 mg/kg carbidopa + diethylpropion, increased the mitral valve leaflets area. Moreover, there were no other significant changes in cardiovascular, hematic or blood parameters.  https://www.selleckchem.com/products/capsazepine.html  Both combinations induced around 20% body weight loss after 3 months of oral administration. Results suggest that 5-HTP/30 mg/kg carbidopa potentiates the anorectic effect of diethylpropion and phentermine with an acceptable safety profile, but further clinical studies are necessary to establish their therapeutic potential in the obesity treatment.