BACKGROUND AND PURPOSE: Frontotemporal dementia (FTD) is a neurodegenerative disorder characterized by pervasive personality and behavioural disturbances with severe impact on patients and caregivers. In current clinical practice, treatment is based on nonpharmacological and pharmacological approaches. Unfortunately, trial-based evidence supporting symptomatic pharmacological treatment for the behavioural disturbances in FTD is scarce despite the significant burden this poses on the patients and caregivers. METHOD: The study examined drug management decisions for several behavioural disturbances in patients with FTD by 21 experts across European expert centres affiliated with the European Reference Network for Rare Neurological Diseases (ERN-RND). RESULTS: The study revealed the highest consensus on drug treatments for physical and verbal aggression, impulsivity and obsessive delusions. Antipsychotics (primarily quetiapine) were recommended for behaviours posing safety risks to both patients and caregivers (aggression, self-injury and self-harm) and nightly unrest. Selective serotonin reuptake inhibitors were recommended for perseverative somatic complaints, rigidity of thought, hyperphagia, loss of empathy and for impulsivity. Trazodone was specifically recommended for motor unrest, mirtazapine for nightly unrest, and bupropion and methylphenidate for apathy. Additionally, bupropion was strongly advised against in 10 out of the 14 behavioural symptoms, emphasizing a clear recommendation against its use in the majority of cases. CONCLUSIONS: The survey data can provide expert guidance that is helpful for healthcare professionals involved in the treatment of behavioural symptoms. Additionally, they offer insights that may inform prioritization and design of therapeutic studies, particularly for existing drugs targeting behavioural disturbances in FTD.

• Klíčová slova
• drug therapy, expert testimony, frontotemporal dementia, neurobehavioural manifestations, neurodegenerative diseases,
• MeSH
• agrese účinky léků   MeSH
• antipsychotika terapeutické užití   MeSH
• frontotemporální demence * farmakoterapie   MeSH
• impulzivní chování účinky léků   MeSH
• konsensus MeSH
• lidé MeSH
• selektivní inhibitory zpětného vychytávání serotoninu terapeutické užití   MeSH
• vzácné nemoci farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• antipsychotika MeSH
• selektivní inhibitory zpětného vychytávání serotoninu MeSH

Squamate reptiles are a highly diversified vertebrate group with extensive variability in social behavior and sexual dimorphism. However, hormonal control of these traits has not previously been investigated in sufficient depth in many squamate lineages. Here, we studied the hormonal control of male sexual behavior, aggressiveness, copulatory organ (hemipenis) size and sex recognition in the gecko Paroedura picta, comparing ovariectomized females, ovariectomized females treated with exogenous dihydrotestosterone (DHT), ovariectomized females treated with exogenous testosterone (T), control females and males. The administration of both T and DHT led to the expression of male-typical sexual behavior in females. However, in contrast to T, increased circulating levels of DHT alone were not enough to initiate the full expression of male-typical offensive aggressive behavior and development of hemipenes in females. Ovariectomized females were as sexually attractive as control females, which does not support the need for the demasculinization of the cues used for sex recognition by ovarian hormones as suggested in other sauropsids. On the other hand, our results point to the masculinization of the sex recognition cues by male gonadal androgens. Previously, we also demonstrated that sexually dimorphic growth is controlled by ovarian hormones in P. picta. Overall, it appears that individual behavioral and morphological sexually-dimorphic traits are controlled by multiple endogenous pathways in this species. Variability in the endogenous control of particular traits could have permitted their disentangling during evolution and the occurrence of (semi)independent changes across squamate phylogeny.

• Klíčová slova
• Aggressive behavior, Androgens, Dihydrotestosterone, Lizard, Sex recognition, Sexual behavior, Sexual dimorphism, Testosterone,
• MeSH
• agrese účinky léků   fyziologie   MeSH
• androgeny farmakologie   MeSH
• dihydrotestosteron farmakologie   MeSH
• ještěři metabolismus   MeSH
• ovarektomie MeSH
• pohlavní dimorfismus * MeSH
• rozmnožování účinky léků   fyziologie   MeSH
• sexuální chování zvířat účinky léků   fyziologie   MeSH
• testosteron farmakologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• androgeny MeSH
• dihydrotestosteron MeSH
• testosteron MeSH

BACKGROUND AND AIMS: It has been well established that long-term antipsychotic treatment prevents relapse, lowers number of rehospitalisations, and also effectively reduces violent behaviour. Although violent behaviour is not a typical manifestation of schizophrenia or other psychotic disorders, the diagnosis of psychosis increases the overall risk of violence. One of the few modifiable factors of violence risk is adherence with medication. In contrast, non-adherence with drug treatment and subsequent relapse increases risk of violent acts. Non-adherence can be addressed partially by long-acting injectable antipsychotics (LAI). The aim of our review was to examine the role of antipsychotic drugs, especially LAI, in prevention and management of violent behaviour in psychosis. METHODS: This is a non-systematic, narrative review of the data from open, naturalistic, retrospective, and population studies, case series, and post hoc analyses of randomised controlled trials. Search of electronic databases (PubMed, Embase) was performed to identify relevant papers. RESULTS: Nine published papers (3 cross-sectional chart reviews, 4 retrospective studies, 2 prospective, randomised trials) were found. The results indicated positive clinical and antiaggressive effects of LAI in psychotic patients with high risk of violent behaviour. DISCUSSION: Reviewed evidence suggests that secured drug treatment with LAI may have clinical benefit in schizophrenia patients with high risk of violent behaviour. LAI significantly reduced the severity of hostility, aggressivity, number of violent incidents, and criminal offences. These findings are supported further by the empirical evidence from clinical practice, high rates of prescribed LAI to schizophrenia patients in high-security and forensic psychiatric facilities. CONCLUSIONS: Available data encourage the use of LAI in forensic psychiatry, especially during court-ordered commitment treatment.

• MeSH
• agrese účinky léků   MeSH
• antipsychotika aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• injekce MeSH
• léky s prodlouženým účinkem MeSH
• lidé MeSH
• násilí prevence a kontrola   psychologie   MeSH
• psychotické poruchy farmakoterapie   psychologie   MeSH
• schizofrenie (psychologie) MeSH
• schizofrenie farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antipsychotika MeSH
• léky s prodlouženým účinkem MeSH

Oxytocin is a hormone therapeutically used mainly for its peripheral effects during pregnancy in the uterus and breasts. However, additional central effects, i.e. anxiolytic effect, decreased level of social stress and increased empathy have been also observed. Hence, the aim of our study was to evaluate if nasal oxytocin can be used as anxiolytic substance in rhesus monkeys (n=20) and rabbits (n=20). Simultaneously, mean arterial blood pressure, arterial oxygen saturation of hemoglobin and pulse rate were monitored in all the evaluated animals. While rabbits lost righting reflex, monkeys developed a dose-dependent loss of aggressiveness and/or anxiety as evaluated by behavioral methods (aggressive behavior was classified as non-sedated - sedated - strongly sedated).

• MeSH
• agrese účinky léků   fyziologie   MeSH
• anxiolytika aplikace a dávkování   MeSH
• aplikace intranazální MeSH
• hypnotika a sedativa aplikace a dávkování   MeSH
• králíci MeSH
• krevní tlak účinky léků   fyziologie   MeSH
• Macaca mulatta MeSH
• náhodné rozdělení MeSH
• oxytocin aplikace a dávkování   MeSH
• srdeční frekvence účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• anxiolytika MeSH
• hypnotika a sedativa MeSH
• oxytocin MeSH

It has been shown that nitric oxide (NO) increases aggression in male mice, whereas it decreases aggression in lactating female mice and prairie voles. It is also known that aggression can be exhibited at different levels in rodent species, strain or subtypes. The aims of this study were to investigate the proportion of aggressiveness in Wistar rats, the effect of intraperitoneally administered nonspecific nitric oxide synthase (NOS) inhibitor L-NAME (NG-nitro L-arginine methyl ester) on maternal aggression towards female intruders, and whether these effects are due to NO production or not. Rats were given saline intraperitoneally on the postpartum Day 2 and aggression levels were recorded. The same rats were given 60 mg/kg L-NAME or D-NAME (NG-nitro D-arginine methyl ester) on the postpartum Day 3 and their effects on aggression levels were compared to saline. While L-NAME administration did not cause any differences in the total number of aggressive behavior, aggression duration and aggression intensity, it reduced the proportion of animals showing aggressive behavior. In addition, the latency of the first aggression was significantly increased by L-NAME. In the D-NAME group, however, no significant change was found. Our results have shown that L-NAME reduces maternal aggression towards female intruders in Wistar rats through inhibition of NO production. These results suggest that the role of NO in offensive and defensive maternal aggression shares neural mechanisms.

• MeSH
• agrese účinky léků   MeSH
• chování zvířat účinky léků   MeSH
• inhibitory enzymů farmakologie   MeSH
• krysa rodu Rattus MeSH
• mateřské chování účinky léků   MeSH
• NG-nitroargininmethylester farmakologie   MeSH
• oxid dusnatý metabolismus   MeSH
• potkani Wistar MeSH
• synthasa oxidu dusnatého antagonisté a inhibitory   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• inhibitory enzymů MeSH
• NG-nitroargininmethylester MeSH
• oxid dusnatý MeSH
• synthasa oxidu dusnatého MeSH

Alpha-2 adrenoceptors (alpha(2)-ARs) are critically involved in regulating neurotransmitter release from sympathetic nerves and neurons and play an important role in the regulation of awareness, arousal and vigilance. In our recent study, dexmedetomidine, a full alpha(2)-AR agonist, produced antiaggressive effects in the social conflict test in mice at doses that were twice smaller than those producing sedation. The aim of this study was to ascertain antiaggressive effect of a novel drug naphthylmedetomidine, with a more selective alpha(2)-AR activity. Behavioral effects of naphthylmedetomidine (150-1200 microg/kg i.p.) were studied in the activity cage and in the social conflict tests in mice. Naphthylmedetomidine dose dependently decreased aggressive behavior during social conflict in aggressive mice with significant reduction already at the lowest doses tested (150 microg/kg), whereas locomotion and social investigation were significantly decreased only after four times bigger dose of naphthylmedetomidine (600 microg/kg) in aggressive mice. Naphthylmedetomidine had no effect on aggression in nonaggressive mice. Naphthylmedetomidine reduced locomotion in the activity cage significantly only at the highest doses tested (600 and 1200 microg/kg), and this effect was only partially reversed by administration of high doses of an alpha-2 antagonist atipamezole (3 and 10 mg/kg). In nonaggressive mice, the difference between the dose reducing dominant social behavior (social investigation) and locomotion (150 and 300 microg/kg, respectively) was smaller than in aggressive mice. In conclusion, naphthylmedetomidine showed a very strong and selective antiaggressive effect in aggressive mice, which was devoid of locomotion-inhibiting/sedative effect. This study suggests that naphthylmedetomidine may have clinical potential as antiaggressive drug.

• MeSH
• agonisté adrenergních alfa-receptorů farmakologie   MeSH
• agonistické chování účinky léků   MeSH
• agrese účinky léků   MeSH
• alfa-2-adrenergní receptory - agonisté * MeSH
• arousal účinky léků   MeSH
• dominance a subordinace MeSH
• medetomidin analogy a deriváty   farmakologie   MeSH
• myši inbrední ICR MeSH
• myši MeSH
• pohybová aktivita účinky léků   MeSH
• sociální chování MeSH
• sociální izolace MeSH
• sociální prostředí MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• agonisté adrenergních alfa-receptorů MeSH
• alfa-2-adrenergní receptory - agonisté * MeSH
• medetomidin MeSH

Dexmedetomidine is a highly specific alpha2-adrenoreceptor agonist, which is now clinically used to induce sedation in patients in the intensive care units. Behavioural effects of dexmedetomidine have been little studied so far. The drug was reported to reduce behaviour such as locomotion or measures of anxiety or aggression in animals. The aim of the present study was to ascertain whether dexmedetomidine inhibits behaviour uniformly or with respect to particular stimuli or situations. Therefore, behavioural effects of dexmedetomidine were studied in the social conflict test in male mice (after three weeks of individual housing), which provides a wide spectrum of behavioural activities in two types of animals (aggressive and sociable mice) as well as in the activity cage. Dexmedetomidine (5-40 microg/kg i.p.) decreased locomotion in the activity cage and this effect was fully antagonized by atipamezole, a selective alpha2-adrenereceptor antagonist. However, dexmedetomidine did not reduce locomotion during social conflict. The only significant effects during social conflict were a selective and dose-dependent antiaggressive effect in aggressive mice and a selective reduction of social investigation ('sociability') in sociable mice. Thus, dexmedetomidine appears to inhibit predominantly dominant behaviour evoked by biologically important stimuli. The ability of dexmedetomidine to reduce aggression might be utilized for treatment of aggressive states. Sedation caused by dexmedetomidine can be easily disrupted and thus the drug may have an advantage over benzodiazepines or neuroleptics, which are used in this indication.

• MeSH
• agonisté adrenergních alfa-receptorů aplikace a dávkování   farmakologie   MeSH
• agrese účinky léků   MeSH
• alfa blokátory aplikace a dávkování   farmakologie   MeSH
• alfa-2-adrenergní receptory účinky léků   MeSH
• analýza rozptylu MeSH
• chování zvířat účinky léků   MeSH
• dexmedetomidin aplikace a dávkování   farmakologie   MeSH
• imidazoly aplikace a dávkování   farmakologie   MeSH
• konflikt (psychologie) MeSH
• myši inbrední ICR MeSH
• myši MeSH
• pohybová aktivita účinky léků   MeSH
• sociální chování * MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• agonisté adrenergních alfa-receptorů MeSH
• alfa blokátory MeSH
• alfa-2-adrenergní receptory MeSH
• atipamezole MeSH Prohlížeč
• dexmedetomidin MeSH
• imidazoly MeSH

RATIONALE: Flumazenil, a competitive antagonist of benzodiazepine receptors (BZRs), has been used as a probe to detect effects of putative endogenous ligands for BZRs in anxiety. Flumazenil is renowned for its highly inconsistent behavioral effects. OBJECTIVE: To ascertain effects of flumazenil in the social conflict test in mice, which provides complex measures for prediction of anxiolytic and anxiogenic activity of drugs in behaviorally different groups of animals. METHODS: Singly housed male mice treated with flumazenil (5, 20 or 80 mg/kg i.p.) or vehicle were paired with untreated non-aggressive group-housed male mice in a novel cage. Behavior was analyzed from video tapes of the social interactions in three populations of mice: timid (n=21), aggressive (n=11), and sociable (n=7). Levels of gamma-aminobutyric acid (GABA) were measured in vivo in the prefrontal cortex. RESULTS: Flumazenil reduced timid (defensive-escape) and increased locomotor activities in timid mice. The drug reduced aggressive and increased sociable (social investigation) activities in aggressive mice. These behavioral changes were produced at the lowest dose of flumazenil tested (5 mg/kg) and were not increased further by higher doses of the drug (20 mg/kg or 80 mg/kg). A tendency to increased timidity was found after flumazenil in sociable mice. Concentrations of GABA were markedly higher in the prefrontal cortex of sociable mice than in timid or aggressive mice. CONCLUSIONS: Flumazenil produced moderate anxiolytic-like behavioural changes and a slight anxiogenic-like effect. The present data might be reflecting antagonism of corresponding endogenous BZR ligands. However, these putative ligands seem to exert only modest modulatory influence.

• MeSH
• agrese účinky léků   fyziologie   MeSH
• flumazenil farmakologie   MeSH
• konflikt (psychologie) * MeSH
• myši inbrední ICR MeSH
• myši MeSH
• pohybová aktivita účinky léků   fyziologie   MeSH
• sociální chování * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• flumazenil MeSH

3alpha-Hydroxy-20-oxo-5alpha-pregnan-21-yl hemisuccinate (8) was produced by partial acylation of 3alpha,21-dihydroxy-5alpha-pregnan-20-one (14). 3alpha-Fluoro-5alpha-pregnan-20-one (9) was prepared by treatment of 3beta-hydroxy-5alpha-pregnan-20-one (11) with DAST and by solvolysis of tosylate 12 with tetrabutylammonium fluoride. A behavioral test on mice was performed using 3alpha-hydroxy-5alpha-pregnan-20-one (1) and compounds 8 and 9. Compound 8 was found to be inactive, while the fluoro derivative 9 selectively reduced aggressive behavior in mice more than the corresponding 3alpha-hydroxy compound 1; locomotion and other behavioral features were not affected.

• MeSH
• agrese účinky léků   MeSH
• myši inbrední ICR MeSH
• myši MeSH
• pregnanolon analogy a deriváty   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• pregnanolon MeSH

The study examined the effects of the benzodiazepine receptor partial agonist, Ro 19-8022, on anxiety-like, aggressive, social and locomotor behaviours in timid ('anxious') and aggressive mice in the social conflict test. To test the hypothesis that Ro 19-8022 acts as a partial agonist in this model, i.e. it reduces anxiety-like and aggressive behaviours without affecting motor coordination, its effects were compared to those of the full agonist, nitrazepam. Both Ro 19-8022 and nitrazepam decreased anxiety-like behaviour in timid mice and aggressive behaviour in aggressive mice. The effect of the full agonist, nitrazepam, was dose-dependent while the effect of the partial agonist, Ro 19-8022, was lower in magnitude and reflected its partial agonistic properties. Both drugs stimulated social behaviour in both groups of mice, presumably due to disinhibition of anxiety or aggression. The marked difference was in their effects on motor coordination, as nitrazepam, but not Ro 19-8022, produced motor impairment at higher doses. Thus, Ro 19-8022 produces anxiolytic-like and potent anti-aggressive effects without causing muscle relaxation or ataxia in the present model. Our data confirm that the main behavioural differences between partial and full benzodiazepine receptor agonists are in their side-effect profiles.

• MeSH
• agonisté receptorů GABA-A * MeSH
• agrese účinky léků   MeSH
• anxiolytika farmakologie   MeSH
• chinoliziny farmakologie   MeSH
• chování zvířat účinky léků   MeSH
• GABA modulátory farmakologie   MeSH
• konflikt (psychologie) * MeSH
• myši inbrední ICR MeSH
• myši MeSH
• nitrazepam farmakologie   MeSH
• pyrrolidiny farmakologie   MeSH
• sociální chování * MeSH
• úniková reakce účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• agonisté receptorů GABA-A * MeSH
• anxiolytika MeSH
• chinoliziny MeSH
• GABA modulátory MeSH
• nitrazepam MeSH
• pyrrolidiny MeSH
• Ro 19-8022 MeSH Prohlížeč