Antipsychotic, antidepressant, and cognitive-impairment properties of antipsychotics : rat profile and implications for behavioral and psychological symptoms of dementia

Many dementia patients exhibit behavioral and psychological symptoms (BPSD), including psychosis and depression. Although antipsychotics are frequently prescribed off-label, they can have marked side effects. In addition, comparative preclinical studies of their effects are surprisingly scarce, and strategies for discovery of novel pharmacotherapeutics are lacking. We therefore compared eight antipsychotics in rat behavioral tests of psychosis, antidepressant-like activity, and cognitive impairment as a basis for preclinical evaluation of new drug candidates. The methods used in this study include inhibition of MK-801-induced hyperactivity, forced swim test (FST), passive avoidance (PA), spontaneous locomotor activity, and catalepsy. The drugs exhibited antipsychotic-like activity in the MK-801 test but with diverse profiles in the other models. Risperidone impaired PA performance, but with some dose separation versus its actions in the MK-801 test. In contrast, clozapine, olanzapine, lurasidone, and asenapine showed little or no dose separation in these tests. Aripiprazole did not impair PA performance but was poorly active in the MK-801 test. Diverse effects were also observed in the FST: chlorpromazine was inactive and most other drugs reduced immobility over narrow dose ranges, whereas clozapine reduced immobility over a wider dose range, overlapping with antipsychotic activity. Although the propensity of second-generation antipsychotics to produce catalepsy was lower, they all elicited pronounced sedation. Consistent with clinical data, most currently available second-generation antipsychotics induced cognitive and motor side effects with little separation from therapeutic-like doses. This study provides a uniform in vivo comparative basis on which to evaluate future early-stage drug candidates intended for potential pharmacotherapy of BPSD

THE EFFECT OF SELECTED POLYMORPHISMS OF THE DOPAMINE RECEPTOR GENE DRD2 AND THE ANKK-1 ON THE PREFERENCE OF CONCENTRATIONS OF SUCROSE SOLUTIONS IN MEN WITH ALCOHOL DEPENDENCE

Background: The aim of the study was to determine the influence of DRD2 gene polymorphisms in exon 8 G/A (rs 6276) in the promoter region -141 C Ins/Del (rs1799732) and the influence of ANKK-1 gene Taq-1A polymorphism (rs 1800497) on the preference of increasing sucrose concentrations in men with alcohol dependence. Subjects and methods: 63 male patients with alcohol dependence were genotyped for the above polymorphisms. Their preference for increasing sucrose concentrations was tested and their taste intensity perception of sucrose solutions was assessed. The patients were tested with the \u27Sniffin\u27 Sticks\u27 olfactory test. Results: We found a statistically significant association between some alleles of ANKK 1 gene Taq 1A polymorphisms and sucrose preference in the subjects. The A1 Taq 1A allele determined hedonistic response to the two highest concentrations of sucrose. No association was found regarding the other two polymorphisms (in the promoter region and in the exon 8 of the DRD2 gene). Conclusions: Study results suggest Taq-1A polymorphism plays a role in the preference to high concentrations of sucrose and its potential association with alcohol dependence pathogenesis

Prevalence and influence of cys407* Grm2 mutation in Hannover-derived Wistar rats:mGlu2 receptor loss links to alcohol intake, risk taking and emotional behaviour

AbstractModulation of metabotropic glutamate 2 (mGlu2) receptor function has huge potential for treating psychiatric and neurological diseases. Development of drugs acting on mGlu2 receptors depends on the development and use of translatable animal models of disease. We report here a stop codon mutation at cysteine 407 in Grm2 (cys407*) that is common in some Wistar rats. Therefore, researchers in this field need to be aware of strains with this mutation. Our genotypic survey found widespread prevalence of the mutation in commercial Wistar strains, particularly those known as Han Wistar. Such Han Wistar rats are ideal for research into the separate roles of mGlu2 and mGlu3 receptors in CNS function. Previous investigations, unknowingly using such mGlu2 receptor-lacking rats, provide insights into the role of mGlu2 receptors in behaviour. The Grm2 mutant rats, which dominate some selectively bred lines, display characteristics of altered emotionality, impulsivity and risk-related behaviours and increased voluntary alcohol intake compared with their mGlu2 receptor-competent counterparts. In addition, the data further emphasize the potential therapeutic role of mGlu2 receptors in psychiatric and neurological disease, and indicate novel methods of studying the role of mGlu2 and mGlu3 receptors

Simplified Methodology of Electromagnetic Field Measurements in the Vicinity of 5G Massive MIMO Base Station for Environmental Exposure Assessment

The development of wireless systems technologies consists, on the one hand, in new methods of generating a radio signal and, on the other hand, in optimizing the transmission of this signal, for instance, by using modern multiantenna technology. This is particularly visible in cellular systems, especially 5G, where network capacity, link throughput and energy optimization are very important. Changes in technology are followed by the need to adapt methods for measuring the electromagnetic field strength in the vicinity of the base station to new cellular standards, mainly because of the introduction of features that allow for real time change in radiation pattern and power distribution. This paper presents basics of multiantenna systems and beamforming techniques for modern cellular networks and the related consequences of evaluating electromagnetic field distribution in the vicinity of such installations for the purpose of compliance with the applicable radio frequency exposure limits. Measurement methods are presented together with the proposal for the optimized and simplified methodology, which can be used for the in-situ electromagnetic field exposure assessment in the vicinity of base stations with multiantenna systems and the configured maximum transmitted power. The measurement methodology has been verified empirically

THE EFFECT OF SELECTED POLYMORPHISMS OF THE DOPAMINE RECEPTOR GENE DRD2 AND THE ANKK-1 ON THE PREFERENCE OF CONCENTRATIONS OF SUCROSE SOLUTIONS IN MEN WITH ALCOHOL DEPENDENCE

Background: The aim of the study was to determine the influence of DRD2 gene polymorphisms in exon 8 G/A (rs 6276) in the promoter region -141 C Ins/Del (rs1799732) and the influence of ANKK-1 gene Taq-1A polymorphism (rs 1800497) on the preference of increasing sucrose concentrations in men with alcohol dependence. Subjects and methods: 63 male patients with alcohol dependence were genotyped for the above polymorphisms. Their preference for increasing sucrose concentrations was tested and their taste intensity perception of sucrose solutions was assessed. The patients were tested with the \u27Sniffin\u27 Sticks\u27 olfactory test. Results: We found a statistically significant association between some alleles of ANKK 1 gene Taq 1A polymorphisms and sucrose preference in the subjects. The A1 Taq 1A allele determined hedonistic response to the two highest concentrations of sucrose. No association was found regarding the other two polymorphisms (in the promoter region and in the exon 8 of the DRD2 gene). Conclusions: Study results suggest Taq-1A polymorphism plays a role in the preference to high concentrations of sucrose and its potential association with alcohol dependence pathogenesis

Magnesium Status and Stress: The Vicious Circle Concept Revisited

International audienceMagnesium deficiency and stress are both common conditions among the general population, which, over time, can increase the risk of health consequences. Numerous studies, both in pre-clinical and clinical settings, have investigated the interaction of magnesium with key mediators of the physiological stress response, and demonstrated that magnesium plays an inhibitory key role in the regulation and neurotransmission of the normal stress response. Furthermore, low magnesium status has been reported in several studies assessing nutritional aspects in subjects suffering from psychological stress or associated symptoms. This overlap in the results suggests that stress could increase magnesium loss, causing a deficiency; and in turn, magnesium deficiency could enhance the body's susceptibility to stress, resulting in a magnesium and stress vicious circle. This review revisits the magnesium and stress vicious circle concept, first introduced in the early 1990s, in light of recent available data