Biomedical subjects

D Treit

Publications and source records attributed to D Treit.

At least 37 records · Page 2Linked to original sources

PubMed1995

The central and basolateral amygdala differentially mediate the anxiolytic effects of benzodiazepines.

Microinfusions of the benzodiazepine anxiolytic midazolam into the central or basolateral amygdaloid nuclei produced different anxiolytic effects in two tests of rat 'anxiety'. Infusions into the basolateral nucleus impaired open-arm avoidance in the elevated plus-maze test, but did not impair shock-probe avoidance in the shock-probe burying test. In contrast, infusions into the central nucleus impaired shock-probe avoidance, but did not impair open-arm avoidance. Both of these site-specific, midazolam-induced anxiolytic effects were blocked by a pre-infusion of the benzodiazepine receptor antagonist Ro 15-1788 (flumazenil). None of the treatments affected defensive burying. These results suggest that benzodiazepine receptors in the central and basolateral amygdaloid nuclei differentially mediate the anti-anxiety effects of benzodiazepine anxiolytics.

Amygdala↗

PubMed1994

The septum and amygdala differentially mediate the anxiolytic effects of benzodiazepines.

Microinfusions of a benzodiazepine anxiolytic (midazolam) into the septum or the amygdala suppressed different fear reactions in two tests of rat "anxiety". Septal infusions increased open-arm activity in the plus-maze test and decreased burying behavior in the shock-probe test whereas amygdaloid infusions produced neither of these antianxiety effects. Amygdaloid infusions, however, dramatically impaired shock-probe avoidance, an antianxiety effect not produced by the septal infusions. Infusions of the benzodiazepine receptor antagonist Ro 15-1788 (flumazenil) blocked each of these specific, anti-fear effects of midazolam without producing intrinsic effects by itself. These results suggest that benzodiazepine receptor systems within the amygdala and the septum differentially mediate specific fear reactions.

Amygdala↗

PubMed1993

Anxiolytic effects of serotonergic interventions in the shock-probe burying test and the elevated plus-maze test.

Although serotonergic neural systems have been implicated in the control of anxiety for a number of years, evidence in favour of this role is controversial. The present experiments were designed to further characterize the putative role of serotonin (5-HT) in anxiety, using two pharmacologically validated animal models: the elevated plus-maze and the shock-probe burying tests. If the integrity of 5-HT neural systems is necessary for the expression of 'anxious' behaviors, then disruption of 5-HT systems should produce effects in the plus-maze and shock-probe tests that are similar to those of anxiolytic drugs. In the present experiments, serotonergic function was disrupted in rats, either by chemical depletion using the synthesis inhibitor p-CPA, by inhibitory autoreceptor activation using the selective 5-HT1A receptor ligand 8-OH-DPAT, or by electrolytic lesions of the serotonin-containing, dorsal raphe nucleus. p-CPA and dorsal raphe lesions produced robust anxiolytic effects in the elevated plus-maze and the shock-probe burying tests, whereas 8-OH-DPAT produced anxiolytic effects only in the shock-probe burying test, and 'anxiogenic' effects in the elevated plus-maze test. Although these results generally support the view that serotonin plays a role in the expression of 'anxious' behavior, the opposite effects of 8-OH-DPAT in the two behavioral paradigms suggest that the 5-HT1A receptor subtype exerts differential control over different types of experimental anxiety.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1993

Anxiogenic stimuli in the elevated plus-maze.

Untreated rats normally avoid the open arms of the "elevated plus-maze," preferring instead the closed arms, whereas rats treated with antianxiety drugs (e.g., diazepam) show far less open-arm avoidance. Although it has often been assumed that rats avoid the open arms because of novelty, height, or open space, the anxiogenic role of these stimuli in the plus-maze has not been systematically examined. In Experiment 1, rats were repeatedly exposed to the elevated plus-maze with the expectation that their "fear" of the open arms would habituate over trials. Instead, open-arm avoidance actually increased on the second trial and showed no evidence of habituating after 18 trials. In Experiment 2, three 30-min sessions of confinement to the open arms ("flooding") failed to decrease rats' open-arm avoidance. Instead, rats that had received flooding avoided the open arms significantly more than control rats during the first test. Experiment 3 showed that although diazepam-treated rats avoided the open arms less than vehicle-controls on the first test this difference dissipated across test trials. Further, diazepam had no carryover effect on rats' subsequent avoidance of the open arms in a nondrugged state. In Experiment 4, plus-maze height was varied from 50 to 6 cm, but rats did not display more open-arm activity as maze height decreased. In Experiment 5, height cues were manipulated by placing a "floor" 8 cm beneath one open arm while leaving the floor of the other open arm at 50 cm. Rats did not avoid the "low" open arm less than the "high" open arm.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1993

Dissociating the anti-fear effects of septal and amygdaloid lesions using two pharmacologically validated models of rat anxiety.

Effects of septal and amygdaloid lesions were compared in 2 models of rat "anxiety." Septal lesions decreased burying behavior in the "shock-probe burying test" and increased open-arm exploration in the "elevated plus-maze test," whereas amygdaloid lesions produced neither of these anxiolytic effects. However, amygdaloid lesions increased rats' contacts of the electrified probe, an anxiolytic effect not produced by septal lesions. Each of these distinct, anxiolytic effects of septal or amygdaloid lesions were displayed together in animals with lesions of both structures. Furthermore, the magnitude of these anxiolytic effects after combined lesions was comparable to their magnitude after individual lesions. Taken together, these results suggest the amygdala and the septum independently control the expression of different fear-related behaviors.

Amygdala↗

PubMed1993

Noninteractive effects of diazepam and amygdaloid lesions in two animal models of anxiety.

The role of the amygdala in mediating the anxiolytic effects of diazepam was examined in two models of rat anxiety. As in our previous experiments, amygdaloid lesions by themselves did not increase rats' exploration of the open arms of the elevated plus-maze or decrease rats' burying of an electrified probe in the shock-probe burying test. However, amygdaloid lesions did increase rats' shock-probe contacts. Diazepam (2 mg/kg) increased open-arm activity and decreased burying behavior to an equal extent in sham-lesioned and amygdala-lesioned rats and had no significant effect on the facilitation of probe contacts induced by amygdaloid lesions. These results suggest that many of the anxiolytic effects of benzodiazepines are not mediated by the amygdala.

Amygdala↗

PubMed1992

Excitotoxic lesions of the septum produce anxiolytic effects in the elevated plus-maze and the shock-probe burying tests.

Our previous research has shown that electrolytic lesions of the posterior septum result in dramatic, antianxiety effects in two different animal models of anxiolytic drug action, i.e., a selective increase in open-arm activity in the elevated plus-maze test, and a selective abolition of defensive burying in the shock-probe burying test. Although these results suggest that posterior regions of the septum play an important role in the expression of anxiety in these tests, it is unclear whether destruction of septal nuclei themselves mediated these effects, since electrolytic lesions also destroy fibers of passage. Accordingly, in the present experiments, the anxiolytic effects of electrolytic lesions of the septum were compared to those of excitotoxic lesions, which preferentially destroy cell bodies, leaving fibers of passage intact. In the first experiment, both electrolytic and kainic acid lesions of the posterior septum produced complete anxiolytic effects in the elevated plus-maze (an increase in the percentage of open-arm entries and percentage of time in open arms), and partial anxiolytic effects in the shock-probe test (an increase in contact-induced probe shocks), compared to sham-lesioned controls. These antianxiety effects could not be attributed to an increase in general activity, or a decrease in reactivity to shock. In the second experiment, excitotoxic lesions of the posterior septum were produced by a more selective agent, quisqualic acid. Quisqualic acid, like electrolytic lesions, produced clear, anxiolytic effects in both the plus-maze and the shock-probe tests, compared to sham-lesioned control. Taken together, these results strongly suggest that cells originating in posterior regions of the septum mediate anxiety-related responses.

Animals↗

PubMed1990

Septal lesions inhibit fear reactions in two animal models of anxiolytic drug action.

The role of the septum in anxiety was studied using two different animal models of antianxiety drug action; i.e., the shock probe-burying test and the elevated plus maze test. Antianxiety effects were observed in both paradigms (i.e., a decrease in probe burying, and an increase in open arm activity) after lesions of the entire septum, compared to sham-lesioned controls (Experiment 1). No differences between lesioned and sham-lesioned rats were found in general activity, shock reactivity, or handling reactivity at the time of the antianxiety tests. A second experiment showed that the antianxiety effects observed in the two paradigms were anatomically specific, since lesions of the posterior septum decreased both indices of anxiety (probe burying and open arm avoidance), whereas lesions of the anterior septum resulted in levels of anxiety that were comparable to those displayed by sham-lesioned controls. Taken together, these results provide convergent evidence that posterior regions of the septum play an important role in the control of anxiety in the rat.

Agonistic Behavior↗

PubMed1990

A comparison of benzodiazepine, serotonin, and dopamine agents in the taste-reactivity paradigm.

Previous studies have shown that rats' positive, palatability-dependent consummatory reactions to infused tastes are selectively facilitated by a benzodiazepine agonist (chlordiazepoxide), and that this effect can be blocked by the coadministration of benzodiazepine antagonists (e.g., Ro 15-1788). The purpose of the present study was to determine whether agents acting at other receptor sites (dopaminergic, serotonergic), which have been shown to modulate food consumption, might also modify rats' palatability-dependent reactivity to infused tastes. In this experiment, the benzodiazepine agonist, diazepam, facilitated positive palatability reactions, while dopaminergic agents (haloperidol, apomorphine, amphetamine) had no significant effects on either positive or aversive reactions. The putative 5-HT1A agonists, buspirone and gepirone, had a general inhibitory action on both positive and aversive palatability reactions. These results are surprising in view of the effects of serotonergic and dopaminergic agents on food and fluid intake. Our results suggest that the benzodiazepine receptor system may play a special role in the neural control of appetite through its enhancement of the positive palatability of tastes. Dopamine systems, by contrast, appear to control food intake by modulating processes that are independent of food affect evaluation.

Amphetamine↗

PubMed1990

A comparison of anxiolytic and nonanxiolytic agents in the shock-probe/burying test for anxiolytics.

The effects of IP midazolam (1.0-3.0 mg/kg), pentobarbital (10-20 mg/kg), ethanol (500-2000 mg/kg), scopolamine (0.05-1.25 mg/kg), chlorpromazine (0.5-5.0 mg/kg), yohimbine (0.5-2.0 mg/kg), and pentylene-tetrazol (5.0-20.0 mg/kg) were compared in the shock-probe/burying test. Consistent with results found previously for chlordiazepoxide and buspirone, the anxiolytic agents midazolam and pentobarbital decreased rats' burying behavior toward a continuously electrified (2 mA) shock-probe, and increased the number of contact-induced probe-shocks rats received. A concurrent decrease in probe-burying and increase in probe-shocks was not reliably observed after ethanol, scopolamine, chlorpromazine, yohimbine, or pentylenetetrazol. Although most of these nonanxiolytic agents produced some suppression of burying behavior at high doses, none of these drugs induced a significant increase in probe-shocks. In fact, pentylenetetrazol, which is believed to be anxiogenic, produced a significant reduction in probe-shocks. Yohimbine, another putative anxiogenic agent, was not active in the present test. In summary, concurrent increases in probe-shocks and decreases in probe-burying seem to be characteristic effects of clinically useful anxiolytic agents, which distinguish them from nonanxiolytic agents.

Animals↗

PubMed1988

A triggered hyperkinesia induced in rats by lesions of the corpus striatum.

The role of the corpus striatum (caudate, putamen, and globus pallidus) in movement control has been suggested to involve the modulation of sensory traffic to downstream motor mechanisms. We report that kainic acid lesions of the posterior corpus striatum, which preferentially spare fibers of passage while destroying striatopallidal neurons, produce a stimulus-sensitive movement pattern in rats that has a highly specific sensory trigger. The triggered choreic movement pattern is not a motor pathology per se, nor a response to diffuse states of arousal or stress, but rather is activated specifically in response to oral sensory stimulation. This sensory-specific hyperkinesia may be relevant to certain human sensorimotor pathologies.

Animals↗

PubMed1988

A comparison of buspirone and chlordiazepoxide in the shock-probe/burying test for anxiolytics.

The effects of chlordiazepoxide (2.5-10.0 mg/kg IP) and buspirone (0.05-1.0 mg/kg SC) were compared by a "blind" observer using the shock-probe/burying test for anxiolytics. Both anxiolytic agents decreased rats' burying behavior toward the continuously electrified (2 mA) shock probe, and increased the number of probe-shocks rats received. These bidirectional, anxiolytic drug effects occurred at doses that did not affect the rats' general activity, and these anxiolytic effects generally increased as a function of drug dose. The relative potency of buspirone was substantially greater than that of chlordiazepoxide. These results contrast with those of Craft et al. and suggest that inappropriate methodology may have contributed to the inconsistencies in various results. In any case, under the present parameters, this "repeated shock"-probe test appears to have two advantages over the previous, "single shock" procedure. First, increases in probe-shocks and decreases in probe-burying provide two, concurrent measures of anxiolytic drug effects in the same setting. Second, nearly all subjects receive shock in the repeated shock procedure, compared to only 60-80% of subjects in the single shock procedure. Thus, both in terms of behavioral validity and simple economy, the repeated shock-probe procedure warrants further investigation as a selective test of anxiolytic agents.

Animals↗

PubMed1988

Thigmotaxis as a test for anxiolytic activity in rats.

It has been suggested that "phylogenetically prepared fear reactions" may be useful behavioral assays of the effects of anxiolytic agents. In the present experiments, rats' natural proclivity to stay near the perimeters of a novel environment (i.e., thigmotaxis) was suppressed by anxiolytic agents (diazepam 1-5 mg/kg; chlordiazepoxide 1-10 mg/kg; pentobarbital 1-10 mg/kg), with a relative potency that was similar to their relative potency in the treatment of human anxiety. Furthermore, when effects on general activity were factored out using analysis of covariance, the test also showed some degree of drug-class specificity, since neither d-amphetamine, morphine, nor chlorpromazine produced this anti-thigmotaxic effect. These results support an earlier report that thigmotaxis may be a useful test for anxiolytic activity in rats.

Animals↗

PubMed1987

The direct enhancement of positive palatability by chlordiazepoxide is antagonized by Ro 15-1788 and CGS 8216.

In a previous study, it was found that positive, palatability-dependent consummatory reactions in rats to intraorally infused tastes were facilitated by chlordiazepoxide (10 mg/kg). In contrast, the rats' more neutral or aversive reactions to these tastes were not facilitated by chlordiazepoxide. This suggested that chlordiazepoxide might selectively enhance the positive palatability of tastes. This effect was replicated in the present experiment, and in addition, the benzodiazepine antagonists Ro 15-1788 and CGS 8216 were found to counteract the enhancement of positive ingestive reactions produced by chlordiazepoxide. These antagonist effects generally suggest that the benzodiazepine receptor complex may be involved in making tastes more palatable after chlordiazepoxide administration.

Animals↗

PubMed1987

Ro 15-1788, CGS 8216, picrotoxin, and pentylenetetrazol: do they antagonize anxiolytic drug effects through an anxiogenic action?

Recent evidence suggests that agents that inhibit GABAergic function, particularly at sites on the GABA/benzodiazepine receptor complex, have intrinsic anxiogenic properties. The present experiments further characterize the behavioral effects of these receptor complex inhibitors, using the "defensive burying" test, which is reasonably selective for anxiolytics. Putative blockers of the GABA-receptor coupled chloride channel, picrotoxin and pentylenetetrazol, and the benzodiazepine receptor antagonists Ro 15-1788 and CGS 8216 each blocked the anxiolytic effect of chlordiazepoxide. However, these compounds failed to exert significant anxiogenic effects in the burying test. These findings suggest that different animal models of anxiolytic drug effects are not equally sensitive to the possible anxiogenic effects of drugs that act at the GABA/benzodiazepine receptor complex.

Animals↗

PubMed1986

Caloric regulation in the rat: control by two factors.

These experiments demonstrate that rats can immediately adjust their meal size in response to variations in the caloric density of a novel diet. However, this immediate caloric sensitivity only seems to appear when rats have been adapted to small, calorically insufficient meals. Rats in Experiment 1 were given timed access to unlimited quantities of an oil/water diet during baseline, and they showed no indication of compensating for changes in the caloric density of the oil/water diet during a test meal. Instead, they consumed about the same amount they had consumed during the preceding baseline meal, suggesting that a learned habit of consuming a certain volume of food controlled their meal size. In contrast, rats that were accustomed to receiving only a very small quantity of food for one of their daily meals during baseline immediately responded to the caloric density of an oil/water test diet by consuming a larger meal if the diet was dilute than if it was calorically more concentrated (Experiments 2 and 3). This immediate sensitivity to caloric density occurred whether or not the rats were exposed to the oil/water diet during baseline, suggesting that rats have some way of directly "metering" the caloric density of new foods. Thus, rats' caloric intake during a meal appears to be controlled by two factors: under certain conditions, control is by caloric learning, under other conditions control is by a caloric metering mechanism.

Adaptation, Psychological↗

PubMed1986

The effects of diazepam on "fear" reactions in rats are modulated by environmental constraints on the rat's defensive repertoire.

The simultaneous effects of diazepam on three shock-induced reactions in rats were studied in order to determine the reliability of these behaviors as indices of anxiolytic drug action. Rats were injected with 1 mg/kg of diazepam or vehicle, placed in a 2-compartment chamber containing bedding material, and shocked with 1, 2, or 6 mA when they first touched a wire-wrapped prod attached to one end of the chamber. Diazepam-treated animals displayed significantly less burying behavior, but paradoxically, they also displayed more passive avoidance behavior and fewer exploratory side-transitions than vehicle-injected controls. Defensive burying behavior tended to be negatively correlated with passive avoidance behavior and positively correlated with exploratory side transitions. When the "competitive" relationship between defensive burying and passive avoidance was eliminated by testing rats in a 2-compartment chamber not containing bedding material, diazepam produced a significant suppression of passive avoidance and a significant increase in exploratory side-transitions, compared to control. Taken together, these results suggested that the validity of any single behavioral model of anxiolytic drug action might vary as a function of environmental constraints on the subjects' defensive repertoire.

Animals↗

PubMed1986

Chlordiazepoxide directly enhances positive ingestive reactions in rats.

Benzodiazepines such as chlordiazepoxide (CDP) promote feeding in a number of species. This effect has been interpreted generally to be an indirect consequence of benzodiazepine anti-anxiety action, although some have questioned whether it might not reflect instead a direct action upon the reinforcing properties of foods. The present study employed a behavioral measure that can discriminate between these possibilities: palatability-dependent consummatory actions elicited in rats by tastes. The results suggest that chlordiazepoxide enhances the positive palatability of tastes selectively while having little or no effect on aversive palatability. The net effect is to make tastes more reinforcing following CDP administration.

Animals↗