The effect of the β-carboline FG 7142 on the behaviour of male rats in a living cage: An ethological analysis of social and nonsocial behaviour

The effects of FG 7142, a -carboline benzodiazepine receptor partial inverse agonist, on the social behavior of pair-housed rats were investigated. Four 6-min dyadic social encounters in a living cage were observed in a paradigm in which one member of a pair of rats was injected. The four injection groups (n=8) were vehicle control, and FG 7142 at 2.5, 5.0 and 10.0 mg/kg, respectively. All injections were administered 2 min before the start of the first observation trial. Compared to the effects of vehicle alone, FG 7142 decreased aggressive behaviour but did not change the level of total social interaction. Thus there were compensating increases in approaching and avoiding behaviours following the administration of FG 7142. Locomotion declined marginally and immobility increased in FG 7142-injected rats. FG 7142 decreased the incidence of self-grooming. The evidence is consistent with a relatively selective reduction in intraspecies aggression in male rats after the injection of the -carboline inverse agonist.     

Administration of antidepressants,diazepam and psychomotor stimulants further confirms the utility of Flinders Sensitive Line rats as an animal model of depression

Flinders Sensitive Line (FSL) rats have been proposed as an animal model of depression because they resemble depressed humans in that they have elevated REM sleep, reduced activity, and increased immobility and anhedonia after exposure to stressors. The present paper reviews experiments on the drug treatment of FSL and control Flinders Resistant Line (FRL) rats related to their utility as an animal model of depression, and presents new information. FSL rats exhibited exaggerated immobility in the forced swim test which is counteracted by the tricyclic antidepressants imipramine and desipramine and the serotonin reuptake blocker sertraline; the low immobility exhibited by the FRL rats is generally unaffected by these compounds. In contrast to these therapeutic effects of well recognized antidepressants, lithium and bright light treatment did not alter the exaggerated immobility of FSL rats. Novel data indicated that neither FSL nor FRL rats exhibited alterations in swim test immobility following chronic administration of the psychomotor stimulant amphetamine (2 mg/kg) and the anticholinergic scopolamine (2 mg/kg), which typically reduce immobility after acute administration. However, it was found that the calcium channel blockers verapamil (5 and 15 mg/kg) and nicardipine (10 mg/kg) did reduce the exaggerated immobility in FSL rats following chronic administration, suggesting that these compounds need to be evaluated further in humans. Previous studies have indicated no differences between FSL and FRL rats evaluated in the elevated plus maze, either at baseline or after the administration of diazepam, suggesting that the FSL rat may not differ from controls in anxiety-related behavior. Another recently published study showed that the FSL rat also did not differ from normal Sprague-Dawley rats in startle tests, indicating that the FSL rats do not exhibit behaviors shown in animal models of schizophrenia. These findings confirm the utility of FSL rats as an animal model of depression because the FSL rats do not appear to exhibit behaviors analogous to anxiety or schizophrenia and because they respond therapeutically to antidepressants and not psychomotor stimulants.     

Tai chi for enhanced inpatient mobilization: A feasibility study

ObjectiveTo determine whether utilizing beginner, video-guided tai chi and qigong classes as an adjunct to physical therapy to enhance mobilization among hospitalized patients is feasible and acceptable.DesignSingle-arm feasibility study over a 15½-week period.SettingThree medical-surgical units at one hospital.InterventionsSmall-group video-guided beginner-level tai chi and qigong classes supervised by physical therapists occurred three times a week.Main outcome measuresThe primary outcome was weekly class attendance. Secondary outcomes included patient and staff satisfaction, collected by surveys and semi-structured interviews. Process measures included class duration. Balancing measures included falls.ResultsOne-hundred and fifty-seven patients were referred for recruitment, 45 gave informed consent, and 38 patients attended at least one class. The number of weekly class attendees increased during the study period. Based on first-class experience, 68% (26/38) of patients reported enjoying the class “quite a bit” or “extremely,” 66% (25/38) of patients reported feeling “more mobile” afterward, and 76% (29/38) of patients agreed that the class made them more comfortable going home. Average class duration was 29 minutes. Zero falls occurred during or immediately following class.ConclusionsVideo-guided tai chi and qigong classes are feasible and well-received at our hospital. Future studies of the impact on preserving mobility and function or reducing length of stay are of interest.     

Updating freeze: Aligning animal and human research

Freezing is widely used as the main outcome measure for fear in animal studies. Freezing is also getting attention more frequently in human stress research, as it is considered to play an important role in the development of psychopathology. Human models on defense behavior are largely based on animal models. Unfortunately, direct translations between animal and human studies are hampered by differences in definitions and methods. The present review therefore aims to clarify the conceptualization of freezing. Neurophysiological and neuroanatomical correlates are discussed and a translational model is proposed. We review the upcoming research on freezing in humans that aims to match animal studies by using physiological indicators of freezing (bradycardia and objective reduction in movement). Finally, we set the agenda for future research in order to optimize mutual animal–human translations and stimulate consistency and systematization in future empirical research on the freezing phenomenon.     

Possible non-narcotic component to action of opiate peptides on tonic immobility

Chickens were tested in a tonic immobility paradigm after a single intraperitoneal injection of either 0.0, 0.1, 1.0, 10.0; 100.0, or 1000.0 microgram/kg of the potent opiate analog, (D-Ala2, F5Phe4)-Met-enkephalin-NH2. An inverted-U relationship was obtained, with 100 microgram/kg being the most effective in prolonging immobility. This dose was used in subsequent studies involving pretreatment with naloxone or diluent followed by treatment with diluent, (D-Ala2, F5Phe4)-Met-enkephalin-NH2 (a strong opiate), or (D-Phe4)-Met-enkephalin (a weak opiate). The results indicated that although naloxone had mixed effects in attenuating the duration of tonic immobility, even the analog with negligible opiate activity reliably potentiated the response. Therefore, a component of the effect of opiate peptides on tonic immobility could be due to a non-narcotic action.     

Strain differences of dopamine receptor levels and dopamine related behaviors in rats

Here we have investigated whether differences in levels of dopamine D1-like, D2-like receptors, dopamine D3 receptors, and dopamine transporter could be related to behaviors such as immobility response and locomotion between Wistar rats and Sprague-Dawley rats. The levels of the dopamine receptors and transporter were measured by autoradiographic study at the level of basal ganglia and the limbic subregion. The behavioral study was done by open-field and immobility response tests. The Wistar rats exhibited a higher level of D1 receptor binding in the basal ganglia subregions than Sprague-Dawley rats. The Wistar rats have higher levels of dopamine D2 receptor binding and dopamine transporter binding in the dorsolateral part of the caudate-putamen. In addition, the dopamine transporter binding were also higher in the Wistar rats than in Sprague-Dawley rats in the ventral part of the caudate-putamen and nucleus accumbens core. However, there were no differences in the level of D3 receptor binding in the limbic or basal ganglia subregions between these two strains. In Wistar rats, the duration of the immobility responses was longer and with less locomotor activity after these immobility responses compared with Sprague-Dawley rats. These data suggest that the differences in dopamine receptors in these two rat strains may in part relate to the behavioral differences reported in these two strains.     

Differential roles of hypogastric and pelvic nerves in the analgesic and motoric effects of vaginocervical stimulation in rats

Bilateral transection of the pelvic and/or hypogastric nerves, which convey afferent activity from the reproductive tract, was performed to ascertain the role of these nerves in the analgesic and motoric effects of vaginocervical mechanostimulation (VS) in rats. Two indices of analgesia were used: tail flick latency to radiant heat (TFL) and vocalization threshold to electrical shock of the tail (Voc-T). Nerve cuts were performed at least one week prior to behavioral testing. Bilateral transection of both the pelvic and hypogastric nerves eliminated the analgesic effects of VS on the TFL and Voc-T tests. Bilateral transection of only the pelvic nerves reduced the number of rats showing maximal VS-induced elevation in TFL, without altering the effect of VS on Voc-T. By contrast, bilateral transection of only the hypogastric nerves attenuated the Voc-T-elevating effect of VS, without reducing the effect of VS on elevating TFL. The effects of VS on producing immobility, hindlimb extension and blockage of hindlimb withdrawal to foot pinch were eliminated by combined bilateral pelvic and hypogastric neurectomy. However, bilateral transection of either nerve alone did not significantly alter the efficacy of VS in producing these effects. These findings indicate that the pelvic and hypogastric nerves contribute to the immobility- and extensor-inducing, and flexor-inhibiting effects of VS, and differentially mediate the analgesia-producing effects of VS.     

Guidelines for prevention of venous thromboembolism in immobile patients secondary to neurological impairment

Background. Venous thromboembolism (VTE) is a major cause of morbidity and mortality in hospitalized patients and 7% of these cases are due to immobility secondary to a neurological impairment. Many guidelines are available to guide clinicians dealing with medical or surgical patients. However, and with the exception of spinal injuries, no guidelines are available to deal with other neurologically impaired patients at risk of VTE.

Aim. Our study aimed at gathering evidence from the literature to enable us to deal with the main controversial issues of VTE prevention. Guidelines will be formulated.

Method. A Clinical Standards Group is responsible for the development of clinical guidelines for the Greater Manchester Neurorehabilitation network with services covering a population of around 3 million. The development of VTE prevention guidelines started with the formulation of the main questions, then gathering evidence from the literature to address these questions. Wide consultation then took place. The guidelines were then put before the group for endorsement.

Results. Answers for the main questions such as duration of thromboprophylaxis, TEDS and antiplatelets drugs use were suggested. The resulting document was summarized as a flow chart for use.

Conclusion. We feel that the proposed guidelines are a useful tool for clinicians as they reflect the evidence available from the literature at the moment.     

Changes in plasma testosterone and in its hypothalamic metabolism following immobility responses in rabbits

Plasma testosterone and its metabolism in the hypothalamus has been studied in adult male rabbits following elicitation of an immobility response. Immobility was induced by 2 methods: inversion or clip application. Plasma testosterone levels were significantly reduced in the induction groups (induction not followed by immobility), whereas in the immobility groups did not differ from controls. In the immobility following inversion procedure a negative correlation between plasma testosterone levels and hypnosis duration was found. At central level the in vitro conversion of testosterone to estradiol (aromatization) and to its neutral metabolites was sharply reduced in the immobility groups and, in less extent, in the induction groups. These results indicate that the immobility reaction in the rabbit elicits testosterone metabolism modifications.     

Use of the immobility reflex (“animal hypnosis”) in neuropharmacological studies

The immobility reflex (IR), a reversible, involuntary, immobility response in certain species is advocated as a uniquely useful assay system for testing of psychoactive drugs. One of the two potential areas of application is that measures of IR duration or arousal threshold serve to screen drugs to help establish drug classification, relative potency, and degree of extrapyramidal side effects. Drugs can also be tested for their neural target sites and modes of action by recording electrographic responses in various brain areas during IR. Electrographic activity (EEG, averaged evoked responses, multiple-unit activity) is relatively stable, artifact-free, and less influenced by behavioral feedback and other variables that are problems with alternative experimental preparations. The reversibility of the IR offers the advantages of chronic studies (evaluation of long-term effects, replication of results, and dose-response testing in which each animal can serve as his own control). Results from both areas of application would ultimately need cross- checking by other methods to rule out interactions of IR and the independent variables being tested. Further possible interactions in long-term studies include potential interactions between the degree of tolerance developed to repeated IR trials and to repeated drug administration.