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Introduction: Impulse control disorders (e.g. pathological gambling, hypersexuality) may develop as adverse reactions to drugs. Pathogenetic hypotheses have mainly focused on D3‐receptor agonism, and switching to alternatives with different pharmacologic mechanisms represents a common management strategy. Nonetheless, treatment failure is common and gaining pathophysiological insights is needed. Aim: We aimed to identify targets potentially contributing to pathologic impulsivity. Method: We performed a pharmacovigilance‐pharmacodynamic study on dopamine agonists and antipsychotics using the Food and Drug Administration Adverse Event Reporting System (January 2004–December 2021). We estimated disproportionate reporting using the Bayesian information component. Using online public databases (IUPHAR, ChEMBL, PDSP, DrugBank), we calculated drug occupancies. To identify the targets potentially contributing to impulsivity, we fitted univariate regression models interpolating information components and occupancies within dopamine agonists and antipsychotics. Sensitivity analyses were performed to check for the robustness of the results. Results: Among 19 887 reports of impulsivity, 5898 recorded an antipsychotic, and 3100 a dopamine agonist. The more robust signals concerned aripiprazole (N = 3091; median information component [95% confidence interval] = 4.51[4.45–4.55]) and brexpiprazole (229; 4.00[3.78–4.16]) for antipsychotics, pergolide (105; 5.82[5.50–6.06]) and pramipexole (2009; 5.43[5.36–5.48]) for dopamine agonists. Robust, significant positive associations between drug occupancy and impulsivity reporting were found for D3 within dopamine agonists (beta = 1.52; P‐value = 0.047) and 5‐HT1a within antipsychotics (1.92, 0.029). Conclusion: Our results supported the role of D3‐receptor agonism in inducing impulsivity in dopamine receptor agonists and identified a potential role of 5‐HT1a receptor agonism in antipsychotics. Investigating these receptors may drive towards a better management of drug‐induced impulsivity. [ABSTRACT FROM AUTHOR]

Objective: Development of alcohol dependence is gradual, requires prolonged exposure to alcohol and reflects neuroadaptive processes in the brain. An understanding of these neuroadaptive processes can lead to novel treatment targets. We recently showed that 7 weeks of intermittent alcohol vapor exposure in rats induces a long-lasting increase of voluntary ethanol consumption, accompanied by changes in gene expression patterns in cingulate cortex and amygdala. These findings prompt the question of whether underlying adaptive processes develop gradually over time or whether a temporal threshold exists for this phenotype conversion to occur. We addressed this question by examining the functional consequences of different exposure durations. Method: Male Wistar rats (N = 43) were exposed to alcohol according to the previously published protocol for 2, 4 or 7 weeks. Following 3 weeks of abstinence to eliminate effects of acute withdrawal, subjects were introduced to voluntary alcohol self-administration in a two-bottle free-choice paradigm with continuous access. Results: Rats exposed to alcohol vapor for 7 weeks displayed a marked increase in voluntary ethanol consumption and a dramatic increase in ethanol preference. In rats exposed for shorter periods (2 and 4 weeks), neither ethanol self-administration nor ethanol preference were increased at any time point. Conclusions: These observations support the existence of a temporal threshold for induction of long-lasting changes in voluntary alcohol consumption. The search for underlying molecular processes should be carried out in this context., DEVELOPMENT OF ALCOHOL DEPENDENCE is gradual, requires prolonged exposure to alcohol and reflects neuroadaptive processes in the brain. A central phenomenon in this process is a transition from low to [...]

Nicotine stimulates dopamine release in the ventral striatum of wild-type mice. However, this effect is not observed in the ventral striatum of beta-2 mutant mice. Mesencephalic dopaminergic neurons from mice lacking the beta-2 subunit do not respond to nicotine any more. In these mutant mice, self-administration of nicotine is reduced. A rise in dopamine release mediated through beta-2-containing nicotine acetylcholine receptors is one of the main substrates for the addictive characteristics of nicotine.

Objectives: The aim of this in vitro study was to evaluate the antimicrobial action of BioPure MTAD (Dentsply Tulsa Dental, Johnson City, TN), Tetraclean, Cloreximid (a mixture of Chlorhexidine (CHX) digluconate and Cetrimide), and 5.25% NaOCl (Ogna Laboratori Farmaceutici, Milano, Italy) against selected endodontic pathogens (Enterococcus faecalis, Porphyromonas gingivalis, and Prevotella intermedia). Materials and Methods: The agar plate diffusion procedure was used to observe the antimibrobial activity of irrigants. Results: Statistical analysis revealed significant effects of the different irrigants on the bacteria colonies. Treatment with 5.25% NaOCl induced a larger zone of microbial inhibition in Prevotella intermedia and Porphyromonas gingivalis (Tukey HSD post-test, P = 0.0001) when compare to MTAD, Tetraclean and CHX. Anyway, MTAD and Tetraclean were more effective to inhibit bacterial growth compared to CHX (P < 0.0001, Tukey HSD post-test). Furthermore, post hoc analysis revealed that MTAD and Tetraclean induced the largest zone of microbial inhibition of Enterococcus faecalis cultured under both aerobic and anaerobic conditions, when compared with 2% CHX and NaOCl (P < 0.0001, Tukey HSD post-test). The control group showed no microbial inhibition. Conclusion: 5.25% NaOCl showed a high antimicrobial activity against anaerobic bacteria. MTAD and Tetraclean showed a high action against both, strictly anaerobic and facultative anaerobic bacteria. Chlorexidine + Cetrimide (Cloreximid) showed the lowest antibacterial activity against both, facultative and strictly anaerobic bacteria tested.

Purpose: No clinical evidence–based data on a possible negative influence of osteopenia and harmful lifestyles on implant osseointegration have been published to date. However, chronic alcohol abuse has been related to a progressive osteoporotic state. The continuous effort on developing better performing surfaces might offer improvement in osseointegration rates in conditions of poor bone quality. The aim of the present study was to investigate, in vitro, the behavior of osteoblasts obtained from rats exposed to ethanol vapor for 7 weeks and cultured on an innovative titanium surface achieved by a double anodic spark deposition. Materials and Methods: Ethanol-exposed and unexposed (control) osteoblasts were cultured on an anodic spark–deposited titanium surface and compared to those cultured on an acid-etched one. Cell proliferation and synthesis of alkaline phosphatase, osteocalcin, collagen I, transforming growth factor-β1, interleukin-6, and tumor necrosis factor-α were measured at 3, 7, and 14 days of culture. Results: When cultured on the anodic spark–deposited titanium surface, ethanol-exposed osteoblasts recovered proliferation impairment. Anodic spark–deposited titanium surfaces significantly improved both ethanol-exposed and unexposed osteoblast bioactivity, particularly with regard to alkaline phosphatase and transforming growth factor-β1. Moreover, interleukin-6 release for ethanol-exposed osteoblasts was significantly reduced by the anodic spark–deposited titanium surface. Conclusion: Proliferative and synthetic cell processes altered by ethanol contact were positively and partially restored by contact with the tested innovative surface. [ABSTRACT FROM AUTHOR]