Recent developments in anxiety, stress, and depression

doi:10.1016/0091-3057(95)02175-2

Pharmacology Biochemistry and Behavior

Volume 54, Issue 1, May 1996, Pages 3-12

https://doi.org/10.1016/0091-3057(95)02175-2 Get rights and content

Abstract

Recent research in the development, analysis, and pharmacology of animal tests of state anxiety is discussed, including the use of responses to predator odours, the role of learning in modifying the anxiety measured in the plus-maze, and the roles of cholinergic, NMDA, and dopaminergic systems. Developmental and genetic factors are considered with particular reference to the development of tests of trait anxiety. The roles of 5-HT_1A receptors in anxiety, depression, impulsivitity, and agonistic behaviours are discussed. Recent studies on the impacts of stress on neurotransmitter, endocrine, and immune systems and the interactions between these systems are discussed, with particular emphasis on their contributions to the development of pathologic states relevant to anxiety and depression.

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Approximately more than 50% of patients with depression have the co-occurrence of anxiety, which complicates the treatment of disease. Recently, social isolation stress (SIS) paradigm has been suggested as an animal model to investigate the underlying mechanism involved in depression–anxiety co-occurrence. In this study, applying six weeks of SIS to adolescent mice, we tested whether nitrergic system plays a role in co-occurrence of depression and anxiety. In this study, comparisons between socially and isolated conditioned (SC and IC) animals showed that SIS induces behaviors relevant to depression and anxiety in IC mice and in addition, nitrergic system is involved in mediating the negative outcomes of SIS. Administration of subeffective doses of aminoguanidine (a specific inducible nitric oxide synthase inhibitor or iNOS, 50 mg/kg) and L-NAME (non-specific inhibitor of NOS, 10 mg/kg) significantly reversed the negative effects of SIS on behavioral profile as well as nitrite levels in the cortex of IC mice, Although administration of subeffective dose of 7-nitroindazole (a specific neuronal NOS inhibitor, 25 mg/kg) decreased the nitrite levels in the hippocampus, but had no effect on depressant and anxiogenic effects of SIS. Results of this study confirmed that SIS is an appropriate animal model to investigate the potential mechanisms in depression–anxiety co-occurrence. We also showed that nitrergic system has contributed to co-occurrence of depression and anxiety in IC mice as an underlying mechanism.
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Anxiety and depression are highly comorbid disorders possibly sharing a common neurobiological mechanism. The dysfunction of serotoninergic, noradrenergic and dopaminergic neurotransmission, abnormal regulation in the hypothalamic–pituitary–adrenal axis (HPA), disturbance of cellular plasticity including reduced neurogenesis, or chronic inflammation connected with high oxidative damage play a crucial role in the development of anxiety and depression. The present study was aimed to investigate the effects of atenolol alone and in combination with alprazolam/escitalopram on anxiety, depression and oxidative stress. Wistar albino rats were subjected to 21 day treatment of drugs then exposed to elevated-plus maze (EPM) and modified forced swim test (MFST), and oxidative stress markers were estimated in isolated brain tissue of all groups. The results indicated that atenolol in combination with alprazolam/escitalopram exhibited antidepressant effects by significantly decreasing the immobility and increasing the swimming behavior in the MFST and anti-anxiety effects by increasing the percentage preference and number of open arm entries as well as time spent in open arm in EPM. Pretreatment with atenolol alone and combination with alprazolam/escitalopram also ameliorated tissue glutathione (GSH) and decreased malondialdehyde (MDA) level significantly which explore antioxidant properties of drugs, and combination augments the therapeutic response of monotherapy in depression. In conclusion behavioral and biological findings indicate that the combination of atenolol with alprazolam/escitalopram has the potential of being highly efficacious in treating anxiety and depressive disorders as well as oxidative stress.
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In general terms, EPM is a test used for the assessment of anxiety-related behaviors in rodents [17]. It has been generally suggested that anxiety and stress are interrelated and stress is able to induce anxiety-like behavior [34,35]. Nevertheless, stress and anxiety are two separate phenomena and there is no strict cause-and-effect relation between them [36,37].
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A total of 28 adult male Wistar rats were used in the study. The animals were randomly allocated to four groups. Two of the groups were exposed to white noise stress in a period of 15 days, while the other two groups remained unstressed. One of the stress exposed groups served as the stress control (SC) group and one of the non-stressed groups served as the reference value (RV) group. The remaining two groups were transmission groups. Every two animals of the non-stressed transmission group (TC) have been housed with two other animals of the stress exposed transmission group (TS) during the experimental period. After the stress exposure period, six animals from each group were subjected to behavioral assessment in an elevated plus maze (EPM), and subsequently, their cortisol levels were determined.
White noise exposure of animals in the SC group induced a stress response indicated by an 1.8 fold increase of plasma cortisol level compared to the RV group (2.11 ± 0.43 and 1.16 ± 0,02, respectively). The transmission groups (TS and TC) entered the open arms more frequently and spent more time in open arms compared to the RV group.
White noise exposure caused a stress response characterized by an elevation of cortisol level in rats. The gradual decrease of cortisol level from the SC towards the RV group may be interpreted as an evidence supporting the hypothesis of stress-transmission between cagemates. The moderate stress levels of the transmission groups, but not low and high levels of the SC and RV groups, decreased the anxiety-like behavior, which indicates an inverted U-shaped relationship between stress levels and anxiolytic effectiveness.
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Buspirone, an anxiolytic drug with partial agonist properties at 5-HT1A receptor, has efficacy in the treatment of patients with generalized anxiety disorder (Galdino et al., 2012; Graeff et al., 1996). Therefore, the 5-HT1A receptor could be a pharmacological target that is relevant to the mechanism of action of antianxiety drugs (File, 1996). The possible involvement of the serotonergic system in ellagic acid's mechanism of action was tested using the serotonin synthesis inhibitor, PCPA in the elevated plus-maze test.
Anxiolytic-like effects of dietary flavonoids are relatively well known. Ellagic acid is a naturally occurring flavonoid compound which is abundant in many plants and fruits. The present study was designed to investigate the antianxiety-like effect of ellagic acid in mice using an elevated plus-maze test. The involvement of the GABAergic and serotonergic systems in the antianxiety-like activity of ellagic acid was also studied. Our results showed that ellagic acid treatment (25, 50 and 100 mg/kg, p.o.), produced a significant increase in the percentage of time spent and entry into the open arms, with a profile comparable to that of diazepam (1 mg/kg, p.o.). Unlike diazepam, the anxiolytic doses of ellagic acid did not prolong the duration of sodium thiopental-induced loss of righting reflex, indicating that this flavonoid is non-hypnotic. The anxiolytic effect observed with ellagic acid treatment (25 mg/kg, p.o.) was antagonized by pretreatment with picrotoxin (a non-competitive GABA_A receptor antagonist, 1 mg/kg, i.p.) and flumazenil (a benzodiazepine site antagonist, 1 mg/kg, i.p.) but not with p-chlorophenylalanine (a serotonin synthesis inhibitor, 100 mg/kg, i.p.) and pindolol (a β-adrenoceptors blocker/5-HT_1A/1B receptor antagonist, 10 mg/kg, i.p.). Taken together, the data demonstrated that acute and chronic administration of ellagic acid to mice has produced antianxiety-like effect when tested in the elevated plus-maze. The experiments with different receptor blockers suggest an involvement of GABAergic system in the anxiolytic action of this bioflavonoid. However, this action is not seems to be mediated through serotonergic system.

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ArticleRecent developments in anxiety, stress, and depression

Abstract

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Eur. J. Pharmacol.

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Physiol. Behav.

Physiol. Behav.

Brain Res.

Neurosci. Biobehav. Rev.

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Eur. J. Pharmacol.

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Physiol. Behav.

Biol. Psychiatry

Brain Res. Rev.

Horm. Behav.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Prog. Neuropsychopharmacol.

Behav. Brain Res.

Pharmacol. Biochem. Behav.

J. Affect. Dis.

Physiol. Behav.

Pharmacol. Biochem. Behav.

Physiol. Behav.

Behav. Brain Res.

Pharmacol. Biochem. Behav.

Brain Res.

Psychoneuroendocrinology

Pharmacol. Biochem. Behav.

Physiol. Behav.

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Brain Res.

Pharmacol. Biochem. Behav.

Neuropharmacology

Pharmacol. Biochem. Behav.

Neuropharmacology

Neuropharmacology

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Article
Recent developments in anxiety, stress, and depression