Temperament and character modify risk of drug addiction and influence choice of drugs

Background: Drug addiction and alcoholism involve a complex etiopathogenesis with a variable degree of risk contributions from the host (person), environment, and addictive substances. In this work, temperament and character features of individuals addicted to opiates or alcohol are compared with normal controls to study personality factors in the overall risk for drug addiction. Methods: The study was done in a permissive environment, with easy access to alcohol and heroin, which facilitated analyses of personality factors in drug choice. Participants included 412 consecutive patients (312 opiate addicts, 100 alcohol addicts) treated at the Specialized Hospital for Chemical Dependency in Belgrade, Serbia, and a community sample of 346 controls. Results: Opiate addicts manifested antisocial temperament configuration (high Novelty Seeking, low Reward Dependence) coupled with high Self-transcendence (ie, susceptibility to fantasy and imagination). Alcohol addicts manifested sensitive temperament configuration (high Novelty Seeking coexisting with high Harm Avoidance). Immature personality was observed far more frequently in opiate addicts than in alcoholics or normals. Conclusions: Novelty Seeking appears to be a general risk factor for drug addiction. High Harm Avoidance appears to channel individuals with high Novelty Seeking towards alcoholism. Immature character traits and probable Personality Disorder increase the risk of illegal drugs. Based on equivalent research in nonpermissive environments, at least a portion of our opiate addicts could have developed alcoholism instead in environments with more limited access to opiates. Personality factors provide useful guidelines for preventive work with young individuals with personality risk factors for drug addiction. (Am J Addict 2012;21:462-467).     

Performance monitoring and stop signal inhibition in abstinent patients with cocaine dependence

Impulsivity has been associated with drug abuse and relapse. As a measure of impulsivity, response inhibition in a stop signal task is impaired in substance abusers compared to healthy control subjects. However, cognitive processes besides response inhibition can affect performance in the stop signal task. Greater response readiness to the go signal increases stop signal reaction time (SSRT) and greater performance monitoring elicited by the stop signal decreases SSRT. Prolonged SSRT, therefore, may reflect differences in these other task-related cognitive processes rather than impaired response inhibition. Using a tracking stop-signal task, we compared 18 abstinent cocaine dependent patients with 41 age- and education-matched healthy controls. We computed SSRT for each individual subject on the basis of the horse race model. We also computed the fore-period (FP) effect to measure response readiness to the go signal and the post-signal slowing (PSS) effect to measure performance monitoring to the stop signal. Cocaine subjects showed increased SSRT and decreased PSS effect, compared to healthy controls. Covariance adjustment for the PSS effect eliminated the SSRT difference from healthy controls. These results suggest that diminished performance monitoring can be a critical cognitive mechanism underlying impaired response inhibition in cocaine dependent patients.     

About turn: how object orientation affects categorisation and mental rotation

High-density ERPs evoked by rotated alphanumeric characters were examined to determine how neural processing is affected by stimulus orientation during letter/digit classifications and during mirror/normal discriminations. The former task typically produces response times that are unaffected by stimulus orientation while the latter is thought to require mental rotation. Sensitivity to orientation was first observed around 100-140 ms and this effect was attributed to differences in low-level features between vertical and oblique orientations. Subsequently, character misorientation amplified the N170, a neural marker of object classification, between 160 and 220 ms. Top-down processing is reflected in the ERPs beginning at 280-320 ms and this time range may reflect binding of ventral and dorsal stream information. In the case of mirror-normal discrimination these top-down processes can lead to mental rotation between 340 and 700 ms. Therefore, although neural processing reflects object orientation, these effects do not translate into increases in reaction-times or impaired accuracy for categorisation, and precede those that do in the mental-rotation task.     

Bioavailability of water-soluble CoQ10 in beagle dogs

The bioavailability of a novel water-soluble inclusion complex of CoQ10, prepared in our laboratory was determined and compared with the bioavailability of commercially available oil-based form of CoQ10. Experimental work consisted of single dose comparative bioavailability study on seven beagle dogs, with a 14-day washout period between treatments. Identification and quantification of CoQ10 was done with HPLC-MS method using positive APCI ionization and SIM mode, M+ m/z 863.4. The bioavailability results confirm that the water-soluble formulation has nearly three times higher AUC(0-48 h), two times higher Cmax, and Tmax is shortened from 6 to 4 h.     

N-tert-butyl-alpha-phenylnitrone, a free radical scavenger with anticholinesterase activity does not improve the cognitive performance of scopolamine-challenged rats.

Reversible inhibitors of acetylcholinesterase improve spatial learning and memory in animal models of cognitive impairment. Here we investigate if the beneficial effects of free radical scavenger N-tert-butyl-alpha-phenylnitrone (PBN) on cognitive performance could be explained by its recently discovered anticholinesterase activity. Morris water maze experiment was performed to examine the effect of PBN on the impairment of spatial learning and memory induced by the antagonist of cholinergic muscarinic transmission scopolamine. In situ hybridization histochemistry experiment was performed to study its effects on the induction of immediate early gene expression (c-fos, c-jun) by dopamine D1 receptor agonist SKF-82958 and on the augmentation of the SKF-82958-induced expression of these genes by scopolamine. In both experiments, the effects of PBN were compared to the effects of reversible anticholinesterase physostigmine. We found that physostigmine but not PBN significantly reversed the cognitive impairment in scopolamine-challenged rats, prevented the induction of c-fos and c-jun mRNAs by SKF-82958 and attenuated the augmentation of the SKF-82958-induced expression of these genes by scopolamine. The present experiments did not reveal a significant in vivo anticholinesterase activity of PBN.     

N-tert-butyl-alpha-phenylnitrone, a free radical scavenger with anticholinesterase activity does not improve the cognitive performance of scopolamine-challenged rats

Reversible inhibitors of acetylcholinesterase improve spatial learning and memory in animal models of cognitive impairment. Here we investigate if the beneficial effects of free radical scavenger N-tert-butyl-alpha-phenylnitrone (PBN) on cognitive performance could be explained by its recently discovered anticholinesterase activity. Morris water maze experiment was performed to examine the effect of PBN on the impairment of spatial learning and memory induced by the antagonist of cholinergic muscarinic transmission scopolamine. In situ hybridization histochemistry experiment was performed to study its effects on the induction of immediate early gene expression (c-fos, c-jun) by dopamine D1 receptor agonist SKF-82958 and on the augmentation of the SKF-82958-induced expression of these genes by scopolamine. In both experiments, the effects of PBN were compared to the effects of reversible anticholinesterase physostigmine. We found that physostigmine but not PBN significantly reversed the cognitive impairment in scopolamine-challenged rats, prevented the induction of c-fos and c-jun mRNAs by SKF-82958 and attenuated the augmentation of the SKF-82958-induced expression of these genes by scopolamine. The present experiments did not reveal a significant in vivo anticholinesterase activity of PBN.     

Interactive effects of insulin-like growth factor-1 and beta-estradiol on endothelial nitric oxide synthase activity in rat aortic endothelial cells

Insulin-like growth factor-1 (IGF-1) and beta-estradiol (E2) have vasodilatory effects, in part, through stimulation of vascular nitric oxide (NO) production. However, their interactive effects on endothelial nitric oxide synthase (eNOS) and NO production have not been previously studied in endothelial cells (EC). Employing rat aortic EC (RAEC), the effects of acute (20 and 30 minutes) and prolonged (4 hours) stimulation with 100 nmol/L IGF-1 and 1 nmol/L E2 (alone or in combination) were assessed with respect to protein levels and enzymatic activities for phosphatidyl inositol 3-kinase (PI3K) and serine/threonine kinase Akt (Akt), enzymes involved in eNOS activation. Exposure to IGF-1 for 30 minutes or E2 for 20 minutes increased insulin receptor substrate-1 (IRS-1) association with the regulatory (p85) subunit of PI3K, enhanced tyrosine phosphorylation of p85, and increased PI3K activity. Combined treatment had a greater effect on p85 phosphorylation and PI3K activity then either agonist alone. Moreover, IGF-1 and E2 enhanced Akt Ser(473) phosphorylation, with the effect of IGF-1 being much greater. Acute expose to both E2 (20 minutes) and IGF-1 (30 minutes) were associated with an increase in eNOS activity. Prolonged exposure (4 hours) to either IGF-1 or E2 increased expression of the p85 subunit as well as eNOS activity. Pretreatment with PI3K antagonist wortmannin (WT) prevented this increase in eNOS activity. The results suggest that IGF-1 and E2 may interact through PI3K/Akt-related pathways to increase eNOS activity.