Defense Test Battery Research Articles

Differentiation of anxiolytic and panicolytic drugs by effects on rat and mouse defense test batteries

The use of ethoexperimental techniques to elicit and maximize the full range of defensive behaviors of rats and mice enables a very precise analysis of the effects of drugs on these behavior patterns. Two rat defense test batteries (the fear/defense test battery or F/DTB and the anxiety/defense test battery or A/DTB) have provided evidence that anxiolytic drugs, even from different classes, produce a common pattern of changes in specific behaviors. A recently developed mouse defense test battery (MDTB) has enabled description of mouse defensive behaviors to a predator, for comparison to those of rats, and a series of studies of drug effects on the behaviors measured in the MDTB provides evidence of cross-species generality of anxiolytic drug effects, or lack of effect, on specific defensive behaviors. In addition, tests with panicogenic and panicolytic drugs in the MDTB indicate that these enhance and reduce, respectively, flight reactions, which generally are not altered by anxiolytic compounds. Thus, results from the MDTB, taken in conjunction with those of the two rat test batteries and other defense analyses in rats and mice, provide evidence that many defensive behaviors are similar across rodent species, while the differences obtained provide a consistent pattern across situations. Moreover, the defense test batteries may be used to differentiate the effects of drugs effective against generalized anxiety as opposed to panic, through effects on specific defensive behaviors.

A Comparative Study of the Effects of Selective and Non-Selective 5-HT 2 Receptor Subtype Antagonists in Rat and Mouse Models of Anxiety

Although there is some evidence that compounds acting at 5-HT 2 receptors show anxiolytic activity, little is known about the specific involvement of the different 5-HT 2 receptor subtypes in the modulation of anxiety-related responses. In the present study, the behavioural effects of mianserin, a nonselective 5-HT 2 receptor antagonist, MDL 100,907, a selective 5-HT 2A receptor antagonist, and SB 206553, a selective 5-HT 2B/2C receptor antagonist, were investigated in two rat (the Vogel drinking conflict and the elevated plus-maze tests) and two mouse (i.e. the mouse defense test battery (MDTB) and the light/dark choice test) models of anxiety. Diazepam was used as a positive control. In the Vogel drinking test, mianserin (10 mg/kg) and SB 206553 (3–30 mg/kg), but not MDL 100,907, increased punished responding. Similarly, mianserin (1 mg/kg) and SB 206553 (3–10 mg/kg), but not MDL 100,907, increased entries into the open arms of the elevated plus-maze. These effects are consistent with anxiolytic-like actions of mianserin and SB 206553, although the magnitude of the effects of these two compounds was less than those of diazepam. In addition, in the MDTB, the 5-HT 2 antagonists did not clearly affect the defensive reactions of mice exposed to a rat stimulus and they failed to reverse the avoidance of the illuminated box in the light/dark choice test. These results indicate a lack of anxiolytic-like action of the compounds in mice. These behavioural profiles suggest that blockade of the 5-HT 2A receptor may not reduce anxiety and demonstrate that 5-HT 2B and/or 5-HT 2C receptor subtypes may be primarily involved in the anxiolytic-like effects of mianserin and SB 206553 in rats. © 1997 Elsevier Science Ltd.

Genetic differences in the mouse defense test battery

Genetic differences in the mouse defense test battery

Genetic differences in the mouse defense test battery

The mouse defense test battery (MDTB) has been designed to examine anxiogenic- or anxiolytic-like properties of psychoactive drugs through effects on specific defensive behaviors. In the present study, the MDTB was used to evaluate the potential contribution of genetic factors to these behaviors. The data revealed pronounced differences in several defense reactions among four inbred strains (BALB/c, C57BL/6, CBA, DBA/2) and one outbred (Swiss) mouse line. Thus, when subjects were introduced into the apparatus, Swiss and C57BL/6 displayed the highest levels of horizontal and vertical activities, while BALB/c and DBA/2 mice showed intermediate and CBA low activity rates. When subjects were chased by the rat, C57BL/6 mice used flight as the dominant defense strategy, while the defensive responses of BALB/c, C57BL/6, and DBA/2 mice consisted of flight reactions and risk assessment activities. However, when flight or escape was not possible, risk assessment became the predominant feature of the defense repertoire in the C57BL/6 mice. When defensive threat/attack behaviors were required, Swiss, BALB/c, DBA/2, and C57BL/6 mice showed very similar reactions in terms of the magnitude of the responses observed. CBA mice were poorly defensive in all these test situations. Finally, after the rat was removed from the test apparatus, Swiss, DBA/2, and C57BL/6 mice displayed more vertical activities than BALB/c mice. These latter, however, showed an increased level of ambulation compared to the activity recorded before the rat exposure. Together, these findings indicate that genetic factors contribute to defensive behaviors in this animal model of anxiety. The different behavioral profiles displayed by the strains used here may provide the means to obtain a better insight into the neurobehavioral mechanisms involved in anxiety-related disorders. Aggr. Behav. 23:19–31, 1997. © 1997 Wiley-Liss, Inc.

Evidence that the Behaviors in the Mouse Defense Test Battery Relate to Different Emotional States: A Factor Analytic Study

The Mouse Defense Test Battery (MDTB) has been designed to investigate defensive responses of Swiss-Webster mice conronted with a natural threat, a rat. These behaviors include flight, avoidance, defensive threat/attack reactions, and risk assessment activities. In the present study, a factor analysis was used to examine potential relationships between these behavioral responses. Five independent Factors were extracted from the 17 parameters obtained in the MDTB. Both Factor 1 and Factor 2 include cognitive aspects of defensive behaviors that appear to be related to the process of acquiring and analyzing information in the presence of threatful stimuli (i.e., risk assessment). Flight/avoidance responses heavily loaded on Factor 3 and to a lesser extent on Factor 4. Several defensive threat/attack reactions (i.e., upright postures and biting) highly loaded on Factor 4 and biting also loaded on Factor 3. Finally, the variables that loaded highly on Factor 5 were the number of wall rearings and climbings following the removal of the rat and the immobility time when the subject was trapped in a straight alley. Although the meaning of this latter Factor is not clear at present, Factors 1 to 4 seemingly relate to anxiety. Taken together with recent drug findings from the MDTB, the present analysis further supports the idea that this model provides measures that reflect different aspects of anxiety.

S.22.03 - Panic disorder: Do we know the best way to treat it?

The Mouse Defense Test Battery (MDTB) has been designed to investigate defensive responses of Swiss-Webster mice confronted with a natural predator, a rat. These behaviors include flight, avoidance, defensive threat/attack responses, and risk assessment activities. Previous studies with the MDTB have suggested that this model may have some utility for the investigation of panicogenic and antipanic compounds. In the present study the MDTB was used to investigate the effects of acute (0.05-1 mg/kg, i.p., 30 min) or chronic (0.5-2 mg/kg, one daily i.p. injection during 10 days) treatment with the benzodiazepine receptor (BZPR) full agonist and panicolytic agent alprazolam. At non motor-impairing doses (0.05-0.5 mg/kg), acute alprazolam failed to alter the avoidance distance between the subject and the predator, the number of avoidances when the rat is approaching, predator assessment activities, defensive threat/attack responses when contact is forced between the subject and the predator or contextual escape attempts after the predator was removed. This was in contrast to chronic treatment which decreased both avoidance variables at 0.5 and 1 mg/ kg, defensive threat/attack responses at all doses, and predator assessment responses at 0.5 mg/kg. In addition, the latter treatment reduced post-predator potentiation of escape attempts at 2 mg/kg. These results (1) confirm previous findings with the BZPR full agonist chlordiazepoxide, indicating that these compounds generally attenuate antipredator defensive responses in Swiss-Webster mice; (2) support recent data indicating that panic-altering drugs modulate flight/escape reactions, and suggest that the primary mechanism of action of drugs with efficacy against panic disorder may involve neural systems controlling flight; (3) confirm that the MDTB may be useful for the investigation of panicolytic as well as anxiolytic agents.

Further evidence that the mouse defense test battery is useful for screening anxiolytic and panicolytic drugs: Effects of acute and chronic treatment with alprazolam

The Mouse Defense Test Battery (MDTB) has been designed to investigate defensive responses of Swiss-Webster mice confronted with a natural predator, a rat. These behaviors include flight, avoidance, defensive threat/attack responses, and risk assessment activities. Previous studies with the MDTB have suggested that this model may have some utility for the investigation of panicogenic and antipanic compounds. In the present study the MDTB was used to investigate the effects of acute (0.05-1 mg/kg, i.p., 30 min) or chronic (0.5-2 mg/kg, one daily i.p. injection during 10 days) treatment with the benzodiazepine receptor (BZPR) full agonist and panicolytic agent alprazolam. At non motor-impairing doses (0.05-0.5 mg/kg), acute alprazolam failed to alter the avoidance distance between the subject and the predator, the number of avoidances when the rat is approaching, predator assessment activities, defensive threat/attack responses when contact is forced between the subject and the predator or contextual escape attempts after the predator was removed. This was in contrast to chronic treatment which decreased both avoidance variables at 0.5 and 1 mg/ kg, defensive threat/attack responses at all doses, and predator assessment responses at 0.5 mg/kg. In addition, the latter treatment reduced post-predator potentiation of escape attempts at 2 mg/kg. These results (1) confirm previous findings with the BZPR full agonist chlordiazepoxide, indicating that these compounds generally attenuate antipredator defensive responses in Swiss-Webster mice; (2) support recent data indicating that panic-altering drugs modulate flight/escape reactions, and suggest that the primary mechanism of action of drugs with efficacy against panic disorder may involve neural systems controlling flight; (3) confirm that the MDTB may be useful for the investigation of panicolytic as well as anxiolytic agents.

A model of ???antipredator??? defense in Swiss-Webster mice

A mouse defense test battery (MDTB) has been designed to assess defensive reactions of Swiss-Webster mice to situations associated with nonpainful threat. When compared to mice approached by a leather glove, animals confronted with an anesthetized or a conscious rat displayed potentiated flight responses and defensive threat/attack reactions, while risk assessment performances were generally similar in all three conditions. Furthermore, escape attempt responses following removal of the stimulus were higher in the conscious rat condition compared to the two other groups. Taken together, these results suggest that flight reactions and defensive threat/attack responses are specific to the rat, and thus indicate that the MDTB may relate to 'antipredator' defense. In mice confronted with an anaesthetized rat, administration of the benzodiazepine (BZ) receptor full agonist chlordiazepoxide (5-25mg/kg, i.p., 30min) and the BZ partial agonist Ro 19-8022 (0.5-2mg/kg, i.p., 30min) altered one of two risk assessment measures and inhibited defensive attack behaviors, but failed to counter the post-predator increase in escape attempts. In addition, Ro 19-8022 also strongly reduced flight responses. The overall behavioral profile suggests a fear/anxiety-reducing action of both drugs. By contrast, administration of the BZ inverse agonist Ro 19-4603 (0.025-0.1mg/kg, i.p., 30min) reliably released these defensive responses. Interestingly, the BZ antagonist flumazenil (5-20mg/kg, i.p., 30min) manifested differential intrinsic activity depending upon the level of threat. Thus, in a weakly threatening situation, the drug potentiated flight reactions, indicating an inverse agonist-like action, decreased defensive biting in a highly threatening situation, indicating an agonist activity. These findings demonstrated that BZ ligands differently modulated 'antipredator' defense in Swiss-Webster mice, depending upon their intrinsic (positive or negative) efficacy, but also depending upon the defense strategy required by the threat.

Differential modulation of antipredator defensive behavior in Swiss-Webster mice following acute or chronic administration of imipramine and fluoxetine.

The Mouse Defense Test Battery (MDTB) has been designed to assess defensive reactions in Swiss-Webster mice to situations associated with a natural predator, the rat. Primary measures taken before, during and after predator confrontation comprise escape attempts, predator assessment, defensive attack and flight. Previous reports from this laboratory have shown that the panic-promoting drug yohimbine potentiated flight behavior, while long-term treatment with the panicolytic agent alprazolam reduced this response. In order to evaluate further the possibility that the MDTB may represent an effective animal model of panic attacks, the present study investigated the behavioral effect of imipramine and fluoxetine, two serotonin reuptake inhibitors (SRIs) known to alleviate panic symptoms when given on a repeated basis. Both drugs were administered acutely and chronically (one daily IP injection for 21 days) at 5, 10 and 15 mg/kg. Our results showed that a single dose of imipramine or fluoxetine strongly potentiated flight reactions in response to an approaching predator and increased defensive attack toward the rat. This was in contrast to chronic treatment with each drug which dramatically decreased flight responses and defensive attack behaviors. In addition, long-term administration with both SRIs produced a reliable attenuation of predator assessment activities. Taken together, these findings suggest an acute anxiogenic-like effect of imipramine and fluoxetine followed by a fear/anxiety reducing effect after repeated administrations. These results support clinical observations revealing an acute anxiogenic effect of SRIs followed by an anxiolytic and/or panicolytic effect after chronic use, and support previous results suggesting that the MDTB may be useful for the investigation of panic-modulating agents.

5-HT 1A agonists modulate mouse antipredator defensive behavior differently from the 5-HT 2A antagonist pirenperone

The mouse defense test battery (MDTB) has been designed to investigate defensive reactions in Swiss-Webster mice to situations associated with a natural predator, the rat, such as flight, avoidance, defensive threat, defensive attack, and risk assessment activities. The present study evaluated the ability of 8-OH-DPAT (0.05–10 mg/kg, SC, 5) and gepirone (2.5–10 mg/kg, IP, 30), a full- and a partial agonist at 5-HT 1A sites, as well as pirenperone (0.25–1 mg/kg, IP, 30), a preferential 5-HT 2A receptor antagonist, to exert an anxiolytic-like action in the MDTB. The most consistent effect of both 5-HT 1A receptor agonists across tests was a marked reduction in predator assessment activity and defensive attack behavior. In contrast, neither of the two ligands was able to reduce flight responses to the approaching predator, and both failed to reduce in a specific manner contextual defense behaviors after the predator was removed. The 5-HT 2A receptor antagonist pirenperone did not provide significant indication of an anxiolytic effect on predator assessment activity and postpredator potentiation of contextual defense responses, and had negligible influence on antipredator defensive behavior. The most interesting exception to this profile was a dose-related reduction in flight-related measures. In view of previous results indicating that the panic-promoting drug yohimbine increases flight/escape reactions and that the panicolytic compound alprazolam reduces these responses, we tentatively suggest that the preferential 5-HT 2A receptor antagonist pirenperone may have some efficacy in improving panic attacks. In addition, the lack of effect of the 5-HT 1A receptor agonists on these flight responses is consistent with clinical findings indicating that these agents are of limited use in the treatment of panic disorder. These findings suggest that the MDTB provides behavioural measures capable of differentiating between various classes of antianxiety drugs.

Defensive reactions of “wild-type” and “Domesticated” wild rats to approach and contact by a threat stimulus

Selective breeding of wild rats over many generations on the basis of low or high defensive threat and attack to human approach and contact has produced highly polarized “domesticated” and “wild-type” animals. Because the selection procedure selectively involves these two defense patterns, and these clearly differ in the two groups, it is of interest to determine if other, nonselected, defensive behaviors to threat stimuli also change. “Domesticated” and “wild-type” rats of the thirty-fifth generation were run in a fear defense test battery (F/DTB) to systematically evaluate defensive behaviors to a variety of present threat stimuli. “Domesticated” rats showed reduced avoidance and slower flight speed to an approaching experimenter, reduced jump/startle response to handelap and dorsal contact, less vocalization and boxing to vibrissae stimulation or to an anesthetized conspecific, and reduced defensiveness to an attempted pickup by the experimenter. These results indicate that selective bi-directional breeding for defensive threat and attack to human approach and contact produces group differences in a variety of defensive behaviors, and in defensiveness to stimuli other than those on which the selection was based. © 1994 Wiley-Liss, Inc.

‘Taming’ of wild rats ( Rattus rattus) by 5HT 1A agonists buspirone and gepirone

A battery of tests designed to elicit reactions to a variety of nonpainful threat stimuli was used to study the effects of the 5HT 1A agonists buspirone (5–20 mg/kg), and gepirone (5–20 mg/kg) on the defensive repertoire of wild Rattus rattus. These two compounds produced very similar patterns of results on the test battery, with gepirone generally more effective: Both compounds failed to interfere with either spontaneous motor activity or avoidance/flight to an approaching experimenter. However, both reduced defesive reactivity to proximal threat stimuli, increasing passive contacts with the experimenter in an inescapable situation and reducing “proximal” defensive reactions: jump/flinch reactions to dorsal contact, and, boxing, and biting to a number of threat stimuli. Defensive threat vocalizations and jump attacks were also reduced, but less consistently, as was the experimenter's rating of subject's defensiveness to being picked up. This pattern of results suggested specific “taming” effects of buspirone and, especially, gepirone on defensive reactions. In combination with findings indicating somewhat different (benzodiazepines) to very different (ethanol) profiles for other anxiolytics in the same test battery, these results suggest that the Defense Test Battery may be capable of providing behavioural differentiation among various classes of anxiolytics.

Circulatory and respiratory changes induced by electrical stimulation of limbic system (visceral brain).

ArticlesCIRCULATORY AND RESPIRATORY CHANGES INDUCED BY ELECTRICAL STIMULATION OF LIMBIC SYSTEM (VISCERAL BRAIN)B. K. Anand, and S. DuaB. K. Anand, and S. DuaPublished Online:01 Sep 1956https://doi.org/10.1152/jn.1956.19.5.393MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByGlutamatergic, GABAergic, and endocannabinoid neurotransmissions within the dorsal hippocampus modulate the cardiac baroreflex function in rats15 November 2017 | Pflügers Archiv - European Journal of Physiology, Vol. 470, No. 2Corticolimbic regulation of cardiovascular responses to stressPhysiology & Behavior, Vol. 172Differential effects of infralimbic vs. ventromedial orbital PFC lidocaine infusions in CD-1 mice on defensive responding in the mouse defense test battery and rat exposure testBrain Research, Vol. 1020, No. 1-2Cardiovascular Manifestations of Acute Intracranial Lesions: Pathophysiology, Manifestations, and Treatment30 June 2016 | Journal of Intensive Care Medicine, Vol. 18, No. 3Functional neuroanatomy of the prefrontal cortex: autonomic interactionsNeural Control of the Heart: Central and PeripheralNeurologic Clinics, Vol. 11, No. 2Differential distribution and non-collateralization of central amygdaloid neurons projecting to different medullary regionsNeuroscience Letters, Vol. 97, No. 3Cardiovascular and respiratory responses to electrical and chemical stimulation of the hippocampus in anesthetized and awake ratsBrain Research, Vol. 457, No. 2Differential effects of experimentally induced blood pressure changes on the release of catecholamines in hypothalamic and limbic areas of ratsLife Sciences, Vol. 41, No. 2Projections of supraspinal structures to the phrenic motor nucleus in cats studied by a horseradish peroxidase microinjection methodJournal of the Autonomic Nervous System, Vol. 16, No. 1The involvement of the anterior cingulate cortex in blood pressure controlBrain Research, Vol. 340, No. 1Influence of cerebral cortex stimulation upon cough-like spasmodic expiratory response (SER) and cough in the catBrain Research, Vol. 306, No. 1-2Insular interconnections with the amygdala in the rhesus monkeyNeuroscience, Vol. 6, No. 7Neurophysiology and neuropharmacology of cardiovascular regulation and stressNeuroscience & Biobehavioral Reviews, Vol. 5, No. 1Amygdala central nucleus lesions: Effect on heart rate conditioning in the rabbitPhysiology & Behavior, Vol. 23, No. 6Cardiac arrhythmias in experimental subarachnoid hemorrhage.Stroke, Vol. 8, No. 4Effects of hippocampal lesion on cardiovascular, adrenocortical and behavioral response patterns in micePhysiology & Behavior, Vol. 18, No. 6The Effect of Acute Stroke on Cardiac Functions as Observed in an Intensive Stroke Care UnitStroke, Vol. 5, No. 6Respiratory effects mapped by focal stimulation in the rostral brain stem of the anaesthetised rabbitBrain Research, Vol. 75, No. 1Cardiovascular responses to electrical stimulation of the amygdala in the ratExperimental Neurology, Vol. 39, No. 1Renal failure in intracranial lesionsThe American Journal of Medicine, Vol. 54, No. 2Limbic forebrain and midbrain modulation and phase-switching of expiratory neuronsBrain Research, Vol. 39, No. 1Changes in phrenic activity and heart rate elicited by localized stimulation of amygdala and adjacent structuresElectroencephalography and Clinical Neurophysiology, Vol. 32, No. 1Modulation of spontaneous and reflex activity of the jaw musculature by orbital cortical stimulation in the freely-moving catBrain Research, Vol. 19, No. 1Atrial fibrillation with ventricular slowing in a patient with spontaneous subarachnoid hemorrhageThe American Journal of Cardiology, Vol. 23, No. 3Central nervous system mechanisms mediating cardiac rate and rhythmAmerican Heart Journal, Vol. 74, No. 1ELECTROCARDIOGRAPHIC CHANGES ASSOCIATED WITH A CEREBROVASCULAR ACCIDENTThe Lancet, Vol. 284, No. 7357Renal tubular necrosis following lesions of the brainThe American Journal of Medicine, Vol. 29, No. 2Amygdaloid propagation to the brain stem (electrophysiological study)Electroencephalography and Clinical Neurophysiology, Vol. 12, No. 2 More from this issue > Volume 19Issue 5September 1956Pages 393-400 https://doi.org/10.1152/jn.1956.19.5.393PubMed13367870History Published online 1 September 1956 Published in print 1 September 1956 Metrics