Biomedical subjects

D Treit

Publications and source records attributed to D Treit.

At least 19 recordsLinked to original sources

PubMed2003

Septal GABAergic and hippocampal cholinergic systems interact in the modulation of anxiety.

According to Gray [(1982) The neuropsychology of anxiety: an enquiry into the function of the septo-hippocampal system. Oxford: Oxford University Press; (1991) Neural systems, emotion and personality. In: Neurobiology of learning, emotion, and affect (Madden J, ed), pp 273-306. New York: Raven Press; Gray JA, McNaughton N (2000) The neuropsychology of anxiety. Oxford: Oxford University Press], the septum and the hippocampus act in concert to control anxiety. In the present study we examined a possible interaction between septal GABAergic and hippocampal cholinergic systems in the shock-probe burying test, an animal model of anxiety. In experiment 1, we found that a 10-ng infusion of muscimol in the medial septum produced a significant suppression of burying behavior, whereas lower doses (2.5 and 5.0 ng) did not. In experiment 2, we found a significant suppression of burying behavior after a 20-microg infusion of physostigmine into the dorsal hippocampus, but not after lower-dose infusions (5 and 10 microg). In experiment 3, we infused combined sub-effective doses of physostigmine and muscimol in the hippocampus and medial septum respectively. The combination of sub-effective doses of physostigmine (5 microg) and muscimol (2.5 ng) significantly reduced burying of the shock probe. The results indicate that the hippocampal cholinergic and septal GABAergic systems act synergistically in the modulation of anxiety.

Animals↗

PubMed2001

Systemic EMD 68843 injections reduce anxiety in the shock-probe, but not the plus-maze test.

Selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors and 5-HT(1A) receptor agonists are believed to reduce anxiety. In the present study we examined the effects of injections of 5-(4-[4-(5-cyano-3-indolyl)-butyl]-1-piperazinyl)-benzofuran-2-carboxamide hydrochloride salt (EMD 68843), a 5-HT(1A) receptor agonist and selective 5-HT reuptake inhibitor, in two animal models of anxiety, plus-maze and shock-probe. Rats received intraperitoneal injections of vehicle, diazepam (2.5 mg/kg), or EMD 68843 (10, 20, or 40 mg/kg) 1 h prior to testing. Diazepam at the single dose tested and EMD 68843 dose-dependently (significantly at 20 and 40 mg/kg) reduced burying in shock-probe. However, only diazepam significantly increased open arm exploration in the plus-maze. Therefore, EMD 68843 has task specific anxiolytic properties.

Animals↗

PubMed2001

The anxiolytic effects of intra-hippocampal midazolam are antagonized by intra-septal L-glutamate.

According to Gray [The Neuropsychology of Anxiety: An Enquiry into the Functions of the Septo-hippocampal System, Oxford University Press, New York, 1982], the hippocampus and the septum act in concert to control anxiety. We found that micro-infusion of midazolam into the dorsal hippocampus increased rats' open-arm exploration in the elevated plus-maze. Co-infusion of L-glutamate into the septum suppressed this anxiolytic effect. However, intra-hippocampal midazolam failed to alter rats' burying behavior in the shock-probe test. These findings suggest that the hippocampus and septum work together to regulate rats' behaviors in some (plus-maze) but not all (burying) animal tests of anxiety.

Animals↗

PubMed2000

Amygdala lesions do not impair shock-probe avoidance retention performance.

The present experiment used the shock-probe paradigm, a procedure usually used to assess anxiolytic processes, to assess memory in amygdala-lesioned rats. Rats were placed in a chamber that contained a probe protruding from 1 of 4 walls and were kept there for 15 min after they contacted the probe. For half the rats, the probe was electrified (2 mA). Four days later, sham or neurotoxic amygdala lesions were induced. Retention performance was assessed 8 days later by measuring the latency to contact the probe and the number of contact-induced shocks. The results indicated that, although shock-naive amygdala-lesioned rats were impaired on the 2nd shock-probe test, shock-experienced amygdala-lesioned rats were not. These data indicate that the memory of a shock experience, as indexed with a shock-probe avoidance response, is spared in rats with large amygdala lesions.

Amygdala↗

PubMed2000

Intra-septal infusions of excitatory amino acid receptor antagonists have differential effects in two animal models of anxiety.

Ablation or pharmacological inhibition of the septum produces anxiolytic-like effects in two animal models of anxiety: the elevated plus-maze and the shock-probe burying tests. Overall, these results suggest that the septum normally plays an excitatory role in the control of anxiety-related behaviors. The purpose of the present study was to examine this hypothesis in more detail, by testing the effects of intra-septal infusions of excitatory amino acid (EAA) receptor antagonists on rats' behavior in the shock-probe and plus-maze tests. We found that intra-septal infusions of the non-NMDA (N-methyl-D-aspartic acid) receptor antagonist CNQX (5 microg) suppressed open-arm avoidance in the plus-maze test, and reduced burying behavior in the shock-probe test, without affecting rats' normal avoidance of the shock-probe. In contrast, intra-septal infusions of the NMDA receptor antagonist AP-5 (5 microg) inhibited both shock-probe avoidance and burying behavior, without affecting rats' open-arm avoidance. These dissociations suggest that different EAA receptor types within the septum exert complex but distinct control of different anxiety-related behaviors.

2-Amino-5-phosphonovalerate↗

PubMed1999

Effects of centrally administered anxiolytic compounds in animal models of anxiety.

The effect of intra-cerebrally infused compounds in animal models of anxiety were reviewed. A large body of evidence suggested that benzodiazepine agonists in different brain regions--including areas of the raphe, hypothalamus, periaqueductal gray, septum, hippocampus, and amygdala--produce reasonably consistent anxiolytic effects in a variety of animal models. However, evidence regarding the effects on anxiety of 5-HT1A agonists, 5-HT2 compounds, and 5-HT3 antagonists was somewhat less extensive, both anatomically and behaviourally, and more complex. For example, establishing receptor specificity for 5-HT ligand effects was often complicated by the lack of 'silent' and/or selective antagonists. Neuropeptides had significant effects on anxiety, but these were shown in a smaller number of animal models and in a limited number of brain regions. Regardless of the compounds tested, however, there seemed to be a surprising number of double dissociations (brain site by behavioural test). In fact in some instances, different fear reactions appeared to be controlled by distinct receptor subpopulations within particular parts of the limbic system. These results suggest that the neural control of anxiety might be analogous in organization to sensorimotor systems, i.e., anxiety is controlled by complex systems of multiple, distributed, parallel pathways.

Animals↗

PubMed1999

Characterization of the defensive nature of kindling-induced emotionality.

Long-term amygdala kindling produces substantial changes in emotional behavior in rats. The purpose of these experiments was to determine whether kindling-induced emotionality is fundamentally defensive or aggressive in nature. In Experiment 1, amygdala-kindled rats tested as intruders in a resident-intruder paradigm preferred an active defense strategy (i.e., defensive upright stance, jump attacks), whereas the sham-stimulated rats preferred a passive defense strategy (i.e., freezing). In Experiment 2, amygdala-kindled rats explored an unfamiliar open field significantly less than did the sham-stimulated rats, and they were significantly more resistant to capture from the unfamiliar open field than were the sham-stimulated rats. In contrast, there were no significant differences between the kindled and sham-stimulated rats in resistance to capture from their home cages. These results suggest that the emotionality produced by long-term amygdala kindling is fundamentally defensive in nature.

Aggression↗

PubMed1998

Long-term kindling and interictal emotionality in rats: effect of stimulation site.

Long-term amygdala kindling in rats produces increases in emotionality (Kalynchuk et al., Biol. Psychiatry, 41 (1997) 438-451). The present experiment was conducted to investigate whether this hyperemotionality is specific to amygdala kindling or whether it can be produced by kindling other structures. Rats received 99 convulsive or sham stimulations of either the amygdala, the hippocampus, or the caudate nucleus. One day after the stimulation phase, each rat's open-field activity and resistance to capture were assessed; the following day, each rat was tested on an elevated plus maze. The site of stimulation had a significant effect on the results of each of these tests. The amygdala-kindled and hippocampal-kindled rats explored less in the open field, were more resistant to capture from the open field, and engaged in a greater percentage of open-arm activity in the elevated plus maze than did the caudate-kindled rats or the sham-stimulated controls. The caudate-kindled rats were more active in the open field than their sham-stimulated controls, but they did not significantly differ from them in terms of the other measures. These results suggest that kindling-induced emotionality is produced by limbic kindling but not nonlimbic kindling.

Affective Symptoms↗

PubMed1998

Persistence of the interictal emotionality produced by long-term amygdala kindling in rats.

Long-term amygdala kindling in rats results in large and reliable increases in emotional behaviour that model the interictal emotionality often observed in temporal lobe epileptics [Kalynchuk L. E. et al. (1997) Biol. Psychiat. 41, 438-451; Pinel J. P. J. et al. (1977) Science 197, 1088-1089]. These experiments investigated the persistence of these kindling-induced increases in emotional behaviour after the cessation of the kindling stimulations. In Experiment 1, rats received 99 amygdala or sham stimulations. Then, they were tested on three tests of emotionality (i.e. activity in an unfamiliar open field, resistance to capture from the open field, and activity in an elevated-plus maze) either one day, one week, or one month after the final stimulation. The rats tested one day after the last stimulation displayed substantial decreases in open-field activity, increases in resistance to capture and increases in open-arm activity on the elevated-plus maze; these effects decreased, but not to control levels, in the rats tested one month after the final stimulation. In Experiment 2, rats received 99 amygdala or sham stimulations, and their resistance to capture was assessed one day later. Then, after a 60-day stimulation-free period, the rats received another zero, one, 10, or 30 amygdala stimulations and their resistance to capture was reassessed one day later. The high levels of resistance to capture observed in the rats tested one day after the 99 stimulations declined significantly during the 60-day stimulation-free period, but it remained significantly above control levels. However, the administration of 30 additional stimulations reinstated asymptotic levels of resistance to capture. These results provide the first systematic evidence that kindling-induced increases in emotional behaviour persist at significant levels for at least two months following the termination of kindling stimulations. Thus, they suggest that the neural changes underlying the genesis of interictal emotionality may be closely related to those mediating epileptogenesis itself.

Amygdala↗

PubMed1998

Does the bed nucleus of the stria terminalis mediate fear behaviors?

The bed nucleus of the stria terminalis (BNST) has been implicated in autonomic and hormonal reactions to fearful stimuli, but its role in behavioral reactions to these stressors is less clear. This is puzzling, because 2 closely related areas, the septum and the amygdala, have been repeatedly implicated in fear behaviors. To investigate further, the behavioral effects of BNST lesions were compared to those of septal and amygdaloid lesions in 2 models of rat anxiety: the plus-maze and shock-probe tests. Septal lesions inhibited rats' open-arm avoidance in the plus-maze and suppressed burying of the shock-probe, whereas amygdaloid lesions specifically inhibited shock-probe avoidance. However, BNST lesions produced none of these anti-fear effects; thus, its involvement in the behavioral expression of fear is questionable.

Amygdala↗

PubMed1998

Is barakol anxiolytic?

A recent report suggested that barakol, a biologically active extract of the south-east Asian plant, Cassia siamea, has anxiolytic properties. The purpose of the present study was to replicate and extend these findings by examining the dose-response effects of barakol (0-20 mg/kg) in two pharmacologically validated tests of rat anxiety: the elevated plus-maze and the shock-probe burying tests. Although the purity of our sample of barakol was confirmed by chemical analysis, we found no evidence of its anxiolytic effects in either the plus-maze or shock-probe burying tests.

Analysis of Variance↗

PubMed1998

The septum and the hippocampus differentially mediate anxiolytic effects of R(+)-8-OH-DPAT.

Infusing the 5-HT1A receptor agonist R(+)-8-OH-DPAT into the septum or hippocampus reduced the fear responses of rats differentially in the elevated plus-maze and shock-probe burying tests, two rat models of anxiety. Intra-septal infusions of R(+)-8-OH-DPAT (5 and 10 microg) produced dramatic reductions in rat burying behavior in the shock-probe test, whereas it did not alter rat open-arm activity in the plus-maze test, across a wide range of doses (0.1, 0.25, 5 and 10 microg). Conversely, intra-hippocampal infusions of R(+)-8-OH-DPAT (0.1 and 5 microg/side) produced substantial increases in open-arm activity in the plus-maze test, but did not alter rat burying behavior in the shock-probe test. These dissociations suggest that 5-HT1A receptors in the septum and hippocampus exert parallel but distinct control over different fear reactions.

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

PubMed1997

Changes in emotional behavior produced by long-term amygdala kindling in rats.

The effects of long-term amygdala kindling on emotional behavior were investigated. In Experiment 1, rats received 99 basolateral amygdala, central amygdala, or sham stimulations. The rats in both kindled groups displayed more resistance to capture from an open field and more open-arm activity on an elevated plus maze than did the sham control rats. In Experiment 2, rats received either 20, 60, or 100 amygdala stimulations or sham stimulations. Compared to the sham controls, the kindled rats explored less during the first 30s in a novel open field, avoided the central area of the open field, resisted being captured from the open field, and engaged in more open-arm activity on the elevated plus maze. The magnitude of these effects was greatest in the 100-stim rats and least in the 20-stim rats. Together, these results suggest that long-term amygdala kindling in rats is a useful model for studying the emotionality associated with temporal lobe epilepsy.

Affective Symptoms↗

PubMed1997

Dissociations among the anxiolytic effects of septal, hippocampal, and amygdaloid lesions.

Fear reactions of rats given bilateral lesions to the septum, hippocampus, or amygdala were compared with those of rats given sham lesions, in 2 animal models of anxiety: the shock-probe burying test and the elevated plus-maze test. Septal lesions produced anxiolytic effects in both tests (i.e., an increase in open-arm activity and a decrease in burying), whereas hippocampal and amygdaloid lesions produced neither of these effects. On the other hand, hippocampal and amygdaloid lesions impaired rats' passive avoidance of the electrified shock-probe, whereas septal lesions did not. These dissociations suggest that limbic structures such as the septum, amygdala, and hippocampus exert parallel but distinct control over different fear reactions.

Amygdala↗

PubMed1996

The neuroanatomical specificity of the anxiolytic effects of intra-septal infusions of midazolam.

Microinfusions of the benzodiazepine anxiolytic midazolam into the lateral but not the medial septum suppressed fear reactions in two test of rat 'anxiety'. Midazolam infusions into the lateral septal nuclei increased open-arm exploration in the elevated plus-maze test, and blocked burying behavior in the shock-probe test, whereas midazolam infusions into the medial septum produced neither of these anxiolytic effects. The anxiolytic effects of midazolam in the lateral septum were partially blocked by pre-infusion of the benzodiazepine receptor antagonist Ro15-1788, which had no intrinsic effects by itself. These results suggest that the anxiolytic effects of intra-septal midazolam occur, at least in part, at GABAA-benzodiazepine receptor sites located in the lateral septal nuclei.

Animals↗

PubMed1996

The antidepressant drug phenelzine produces antianxiety effects in the plus-maze and increases in rat brain GABA.

Research on the effects of antidepressant/ antipanic drugs in animal models of anxiety has yielded equivocal results, even after chronic drug regimens. In contrast, we found that the antidepressant/antipanic drug phenelzine, given acutely, produced a clear anxiolytic effect in the elevated plus-maze, a widely-used animal model of "anxiety" that is primarily sensitive to benzodiazepine-type anxiolytics (e.g., diazepam). Furthermore, the effective dose of phenelzine (15 mg/kg) administered to rats was associated with more than a 2- fold increase in whole brain levels of gamma-aminobutyric acid (GABA), whereas an ineffective dose of phenelzine (5.1 mg/kg) did not significantly change GABA levels. The N-acetylated metabolite of phenelzine, N2-acetylphenelzine, produced neither an anxiolytic effect in the elevated plus-maze nor a significant change in whole-brain levels of GABA. However, both phenelzine and N2-acetylphenelzine potently inhibited monoamine oxidase, a mechanism commonly thought to be involved in the therapeutic effects of monoamine oxidase inhibitors such as phenelzine in the treatment of depression in humans. These results suggest that the mechanism whereby phenelzine produces anxiolytic effects in the plus-maze model is unique to a facilitatory action on brain levels of GABA, in contrast to classical benzodiazepines, which produce anxiolytic effects by enhancing the affinity of the GABAA-receptor for GABA.

Animals↗

PubMed1996

Does tolerance develop to the anxiolytic effects of septal lesions?

Previous studies have shown that septal lesions produce anxiolytic-like effects in tests of rat "anxiety" (i.e., septal lesions increase open-arm exploration in the elevated plus-maze test and decrease burying in the shock-probe burying test). The present experiment examined whether "tolerance" develops to the anxiolytic effects of septal lesions, in a manner similar to that of anxiolytic drugs. Accordingly, septal- and sham-lesioned rats were repeatedly tested in the elevated plus-maze. As in previous studies using anxiolytic drugs, septal lesions produced a clear anxiolytic effect on the first test day, but this effect virtually disappeared by the third test day. Although these findings suggest "tolerance" had developed to the anxiolytic effects of septal lesions, these same rats showed clear evidence of anxiolysis when they were subsequently tested in the shock-probe burying paradigm. A second experiment showed that these basic effects did not depend critically on time since surgery. Thus, the diminution of anxiolysis induced by septal lesions in the elevated plus-maze is test-specific and does not reflect a general recovery of normal fear reactions.

Animals↗

PubMed1996

Lateral and medial septal lesions reduce anxiety in the plus-maze and probe-burying tests.

Previous studies have shown that septal lesions produce anxiolytic-like effects in rat models of "anxiety" (i.e., septal lesions, like anxiolytic drugs, increase rats' open-arm exploration in the elevated plus-maze test and decrease rats' burying behavior in the shock-probe burying test). Although these anxiolytic effects occur after lesions to posterior (but not anterior) regions of the septum, their anatomical specificity has not been clearly defined with respect to classical subdivisions of the septum, such as the medial and lateral nuclei. Thus, in Experiment 1, we compared the effects of lateral or medial septal lesions on rats' anxiety reactions in the elevated plus-maze and shock-probe burying tests. Contrary to the "anxiogenic" effects of septal lesions recently found in a "conflict" model of anxiety, we found that both lateral and medial septal lesions produced equivalent anxiolytic effects in the plus-maze and shock-probe tests. In Experiment 2, we found similar anxiolytic effects whenever lesions included septal areas just anterior to the fornix (i.e., the lateral septum) but not when septal lesions were restricted to areas just posterior to the fornix (i.e., the septofimbrial and triangular septal nuclei). Taken together with our previous results, these data suggest that classical subdivisions of the septum bounded rostrally by the genu of the corpus callosum and caudally by the fornix play an exclusively excitatory role in the control of anxiety, as expressed in the plus-maze and shock-probe burying models.

Animals↗