5-Hydroxytryptamine 1A receptors in the dorsomedial hypothalamus connected to dorsal raphe nucleus inputs modulate defensive behaviours and mediate innate fear-induced antinociception.

The dorsal raphe nucleus (DRN) is an important brainstem source of 5-hydroxytryptamine (5-HT), and 5-HT plays a key role in the regulation of panic attacks. The aim of the present study was to determine whether 5-HT1A receptor-containing neurons in the medial hypothalamus (MH) receive neural projections from DRN and to then determine the role of this neural substrate in defensive responses. The neurotracer biotinylated dextran amine (BDA) was iontophoretically microinjected into the DRN, and immunohistochemical approaches were then used to identify 5HT1A receptor-labelled neurons in the MH. Moreover, the effects of pre-treatment of the dorsomedial hypothalamus (DMH) with 8-OH-DPAT and WAY-100635, a 5-HT1A receptor agonist and antagonist, respectively, followed by local microinjections of bicuculline, a GABAA receptor antagonist, were investigated. We found that there are many projections from the DRN to the perifornical lateral hypothalamus (PeFLH) but also to DMH and ventromedial (VMH) nuclei, reaching 5HT1A receptor-labelled perikarya. DMH GABAA receptor blockade elicited defensive responses that were followed by antinociception. DMH treatment with 8-OH-DPAT decreased escape responses, which strongly suggests that the 5-HT1A receptor modulates the defensive responses. However, DMH treatment with WAY-100635 failed to alter bicuculline-induced defensive responses, suggesting that 5-HT exerts a phasic influence on 5-HT1A DMH neurons. The activation of the inhibitory 5-HT1A receptor had no effect on antinociception. However, blockade of the 5-HT1A receptor decreased fear-induced antinociception. The present data suggest that the ascending pathways from the DRN to the DMH modulate panic-like defensive behaviours and mediate antinociceptive phenomenon by recruiting 5-HT1A receptor in the MH.

Risk assessment as an evolved threat detection and analysis process.

Risk assessment is a pattern of activities involved in detection and analysis of threat stimuli and the situations in which the threat is encountered. It is a core process in the choice of specific defenses, such as flight, freezing, defensive threat and defensive attack, that counter the threat and minimize the danger it poses. This highly adaptive process takes into account important characteristics, such as type and location (including distance from the subject) of the threat, as well as those (e.g. presence of an escape route or hiding place) of the situation, combining them to predict which specific defense is optimal with that particular combination of threat and situation. Risk assessment is particularly associated with ambiguity either of the threat stimulus or of the outcome of available defensive behaviors. It is also crucial in determining that threat is no longer present, permitting a return to normal, nondefensive behavior. Although risk assessment has been described in detail in rodents, it is also a feature of human defensive behavior, particularly in association with ambiguity. Rumination may be a specifically human form of risk assessment, more often expressed by women, and highly associated with anxiety. Risk assessment behaviors respond to drugs effective against generalized anxiety disorder; however, flight, a dominant specific defense in many common situations, shows a pharmacological response profile closer to that of panic disorder. Risk assessment and flight also appear to show some consistent differences in terms of brain regional activation patterns, suggesting a potential biological differentiation of anxiety and fear/panic systems. An especially intriguing possibility is that mirror neurons may respond to some of the same types of situational differences that are analyzed during risk assessment, suggesting an additional functional role for these neurons.

Assessment of estradiol influence on spatial tasks and hippocampal CA1 spines: evidence that the duration of hormone deprivation after ovariectomy compromises 17beta-estradiol effectiveness in altering CA1 spines.

Two pulses of 17beta-estradiol (10 microg) are commonly used to increase hippocampal CA1 apical dendritic spine density and alter spatial performance in ovariectomized (OVX) female rats, but rarely are the measures combined. The goal of this study was to use this two-pulse injection protocol repeatedly with intervening wash-out periods in the same rats to: 1) measure spatial ability using different tasks that require hippocampal function and 2) determine whether ovarian hormone depletion for an extended 10-week period reduces 17beta-estradiol's effectiveness in elevating CA1 apical dendritic spine density. Results showed that two injections of 10 microg 17beta-estradiol (72 and 48 h prior to testing and timed to maximize CA1 apical spine density at behavioral assessment) corresponded to improved spatial memory performance on object placement. In contrast, two injections of 5 microg 17beta-estradiol facilitated spatial learning on the water maze compared to rats given two injections of 10 microg 17beta-estradiol or the sesame oil vehicle. Neither 17beta-estradiol dose altered Y-maze performance. As expected, the intermittent two-pulse injection protocol increased CA1 apical spine density, but 10 weeks of OVX without estradiol treatment decreased the effectiveness of 10 microg 17beta-estradiol to increase CA1 apical spine density. Moreover, two pulses of 5 microg 17beta-estradiol injected intermittently failed to alter CA1 apical spine density and decreased basal spine density. These results demonstrate that extended time without ovarian hormones reduces 17beta-estradiol's effectiveness to increase CA1 apical spine density. Collectively, these findings highlight the complex interactions among estradiol, CA1 spine density/morphology, and task requirements, all of which contribute to behavioral outcomes.

[Treatment of dementia]. / Wenn Verhaltensprobleme die Betreuung von Demenzpatienten erschweren.

Some 80% of patients with advanced dementia develop such symptoms as aggression, a tendency to wander away, agitation or shouting and screaming. Often, these symptoms are a reaction to day-to-day problems or to the care-related situation. For this reason, psychopharmaceuticals should be employed only when external causes, additional health disorders or drug-related side effects have been excluded. Therapeutic drug options include modern antidepressants and neuroleptics.

A proposal of decision tree to screen putative antidepressants using forced swim and tail suspension tests.

Interstrain mice variability in response to antidepressant drugs has been reported in the most commonly utilized behavioural animal models of depression: the tail suspension test (TST) and the forced swimming test (FST). The behaviour of mice was examined in both tests for screening various antidepressants with different biochemical mechanism of action. Previous studies have revealed that drug sensitivity depends on the strain and test used. Swiss mice is the most sensitive strain to detect serotonin and/or noradrenaline antidepressants whereas C57BL/6J was the only strain sensitive to bupropion (dopaminergic agent) using the FST. In the TST, all antidepressants studied decreased the immobility time in Swiss and C57BL/6J strains. Detection of an antidepressant-like activity could be performed using only one test (TST with Swiss mice or FST with Swiss and C57Bl/6 Rj mice), but both tests are necessary to conclude on the mechanism of action.

Water and sediment toxicity assessment by use of behavioural responses of medicinal leeches.

Behaviour has been shown to be a sensitive indicator of chemically induced stress and pathology in aquatic organisms. However, ecotoxicological investigations on medicinal leech are restricted because of scarce leech resources in natural waters. We used artificially bred medicinal leech (Hirudo medicinalis L.) of two different ages: young (1-2 weeks old) and adult leeches (1 year old). Animals were exposed to: (1) waters of Lake Drukshiai-the cooler of Ignalina Nuclear Power Plant, (2) sediments of the river Nemunas and (3) solution of heavy metal model mixture (HMMM). The following behavioural responses of leech were investigated: mobility (number of moving individuals within certain periods of time), avoidance response (number of individuals escaping the tested water or sediments) changes in body shape (contractions of some muscles, abnormal position of suckers) and feeding activity (longevity of attachment process, interruptions of feeding bouts, size of blood meal). Mobility of young leeches was increased in the tested waters of Lake Drukshiai, whereas adult leeches showed no changes of this index. Avoidance response as well as impaired feeding activity (prolonged attachment process or completely suppressed attachment reflex, decreased size of blood meal) was observed in young leeches exposed to the waters from Lake Drukshiai and in adult animals exposed to all three kind of trials mentioned above. Avoidance response and changes in mobility were recorded during the first hour of exposure to tested samples; therefore, these responses can be used as an express method for water and sediment pollution assessment. Impaired feeding activity was recorded after 1-3-week exposure: this response may be used in assessing a chronic toxicity of pollution. Medicinal leech, due to its sensitivity, simplicity of measured indices and ease of laboratory maintenance, can be used as a test organism in ecotoxicity studies.

The effects of nicotine on learning and memory: a neuropsychological assessment in young and senescent Fischer 344 rats.

The effects of chronic nicotine on the behavioral performance of young (4 month) and old (24 month) Fischer-344 rats were assessed on four behavioral tasks: activity chamber. rotating rod, serial pattern learning, and Morris water maze paradigm. Old and young nicotine-treated rats received an intraperitoneal injection of nicotine (0.20 mg/kg) 15 min prior to all behavioral testing, and old and young saline-treated rats received saline injections 15 min prior to all behavioral testing. Nicotine improved motor coordination and increased the general activity levels of the old rats compared to old saline-treated rats. There were no significant differences in the behaviors of the young rats in these behavioral evaluations. In young rats, nicotine improved the acquisition of a serial pattern, suggesting an improvement in working memory or related processes. Nicotine was found to increase swim speed in a Morris water maze paradigm with a hidden platform; however, no beneficial effects of nicotine in reference memory were obtained for either age group. These results suggests that nicotine may not be as beneficial in attenuating age-related learning and memory deficits as once proposed.

[Behavioral assessment of neuroleptics (1)--Active avoidance response].

The active avoidance responses in mice and/or rats are suppressed specifically by antipsychotic drugs at the doses which have no marked effect on the general behaviors and the other operant behaviors. In this respect the active avoidance responses have been applied for the preclinical evaluation of antipsychotic drugs. This paper describes accounting points for carrying out the active avoidance test, in particular continuous and discrete avoidance tasks of lever-press and shuttle types in mice and rats. Finally, the typical samples of the avoidance-suppressing effect of antipsychotic drugs (dopamine D2 antagonists) are presented.

Naturalistic behavioral assessment of anxiolytic properties of benzodiazepines and ethanol in mice.

Effects of chlordiazepoxide (CDZ), flurazepam (FLU) and diazepam (DZP) were assessed in mice by observation of digging behavior in an escape task. Reliable effects on escape latencies and number of exploratory head pokes were detected at 2 mg/kg for CDZ and FLU. DZP produced dose-dependent effects at 0.2, 0.4 and 0.6 mg/kg. Ro 15-1788 antagonized the effects of DZP (0.6 mg/kg). Ethanol (0.75 and 1.5 g/kg) produced effects similar to those of the benzodiazepines. The dynamics of this naturalistic behavior avoid the need for direct aversive stimulation or food/water deprivation to set up an approach-avoidance or conflict test. Combined with a multivariate (discriminant) analysis, the approach provides a sensitive assessment of anxiolytic drug activity.

Effects of naloxone upon the behavioural organisation of specific defeat activities in intruder mice: assessment by cluster analysis.

The present experiment examined the effects of naloxone (0.5, 2.5 and 12.5 mg/kg) upon the responses of male Swiss mice to attack by aggressive male conspecifics in the resident-intruder paradigm by measuring the time spent in broad behavioural categories, frequency of individual acts or postures, and performing a cluster analysis of activities according to their frequency and position within the behavioural sequence. The former two measures detected little naloxone-induced change in behaviour. Cluster analysis revealed changes in behavioural organisation which suggested modification in the motivation and/or function underlying specific defeat behaviour.