Behavior In Tail Suspension Test Research Articles

Memantine, an NMDA receptor antagonist, protected the brain against the long-term consequences of sepsis in mice

AimsLong-term neuroinflammation and brain dysfunction have frequently been reported in sepsis survivors. In this study, the protective effect of memantine (an NMDA receptor antagonist) on the long-term consequences of sepsis on the brain was investigated in mice. Materials and methodsEighty-five male C57 mice were included. Memantine was administrated through gavage at 5, 10, and 20 mg/kg three days before sepsis and continued for three days after sepsis induction. Sepsis was induced by intraperitoneal injection of 5 mg/kg LPS. A cohort of mice was sacrificed on the 4th day post sepsis to measure NF-κB, TNF-α, and IL-1β mRNA expression and oxidative stress markers in the brain. The second cohort was used for behavioral tests one month after sepsis induction and then sacrificed for oxidative stress markers and acetylcholinesterase (AChE) activity measurement. Key findingsMDA levels and mRNA expression of NF-κB, TNF-α, and IL-1β ameliorated by memantine at the early days of sepsis induction, and total thiol content and SOD activity were increased. Post-septic mice showed significant disruption of recognition memory in novel object recognition (NOR) and depressive and anxiety-like behaviors in tail suspension test, elevated plus maze (EPM), and open field tests one month after sepsis. Memantine at 10 and 20 mg/kg dose-dependently ameliorated behavioral abnormalities, reduced AChE activity and MDA levels, and enhanced SOD activity and thiol content one month after sepsis. SignificanceThese findings suggest that early treatment of septic mice with memantine could ameliorate brain inflammation and oxidative damage and prevent long-term behavioral consequences of sepsis.

Brain-wide mapping of c-Fos expression with fluorescence micro-optical sectioning tomography in a chronic sleep deprivation mouse model

Chronic sleep deprivation (SD) is a common problem for humans and can lead to many deleterious effects, including depression, anxiety, stroke, permanent cognitive deficits, stress, and other physiological diseases. It is vital to acquire information about the relevant neural activities at the whole-brain level to systematically explore the mechanisms of brain dysfunction related to SD. Expression of the immediate-early gene (IEG) Fos in the mouse brain has been widely used as a functional marker of brain activity in the field of neuroscience. However, most previous studies only analyzed the change of c-Fos in several specific brain regions using traditional research methods or in short-term SD model. Here, we applied c-Fos mapping through the fluorescence micro-optical sectioning tomography (fMOST) technique and AAV-PHP.eB to comprehensive analysis the state of cumulative activation across the whole brain in a mouse model of chronic SD. The chronic rapid eyes movement (REM) SD model was induced by moving mice to a separate holding area filled with water. The experimental period lasted for 6 h per day. The results showed that after 14 days of SD, the mice displayed anxiety-like behaviors in open field test and elevated plus maze test, and displayed depression-like behaviors in tail suspension test and the sucrose preference test. The c-Fos + cells were detected in a maximum of 230 brain regions. SD-induced stress model evoked c-Fos expression in several brain regions compared to the control group. In particular, the isocortex-cerebral cortex plate area, including the retrosplenial, anterior cingulate, agranular insular, gustatory, and parasubiculum, appear to be the most sensitive regions after chronic REM SD.

Electrophysiological Characteristics of Dorsal Raphe Nucleus in Tail Suspension Test.

The dorsal raphe nucleus (DRN) is a major source of serotonin in the central nervous system, which is closely related to depression-like behaviors and is modulated by local GABAergic interneurons. Although serotonin neurons are known to be activated by struggling behavior in tail suspension test (TST), the exact electrophysiological characteristics are still unclear. Here, we combined in vivo electrode recording and behavioral test to explore the mice neuron electrophysiology in DRN during TST and observed that gamma oscillation was related to despair-like behaviors whereas burst fraction was crucial for survival-like behaviors. We reported the identification of a subpopulation of DRN neurons which change their firing rates when mice get into and during TST immobile states. Both increase (putative despair units, D units for short) and decrease (putative survival units, S units for short) in firing rate were observed. Furthermore, using optogenetics to identify parvalbumin-positive (PV+) and serotonin transporter-positive (SERT+) neurons, we found that SERT+ neurons were almost S units. Interestingly, those that have been identified PV+ neurons include ~20% of D units and ~50% of S units. These results suggest that electrophysiological characteristics incorporated in despair-like behavior studies can provide new insight into the study of anti-depression targets, and GABAergic interneuron is a complex key hub to the coding and regulation of local neural network.

Vitamin D3 suppresses astrocyte activation and ameliorates coal dust-induced mood disorders in mice

BackgroundPneumoconiosis patients exhibit significantly more anxiety and depression than healthy individuals. However, the mechanism of coal dust-induced anxiety and depression remains unclear. MethodsA pneumoconiosis mouse model with anxiety- and depression-like behaviors were established after 28 days of exposure to coal dust. Vitamin D3 treatment (1200 IU/kg/week) was administered intraperitoneally for 3 months starting from the first coal exposure. Tail suspension test (TST), open field test (OFT), and elevated plus-maze (EPM) test were used to assess anxiety- and depression-like behaviors. Theserum concentration of 25(OH)D3 and fibrillary acid protein (GFAP) expression were determined. In addition, the morphology and distribution of GFAP and neurogenic differentiation factor1 expression (NeuroD1) in different cerebral hippocampus were observed. ResultsIn coal dust-exposed mice, immobility time decreased in OFT and increased in TST,and the frequency of entering the open arm decreased in the EPM compared with the control mice. Coal dust increased hippocampal GFAP expression and astrocyte activation and reduced neurogenic differentiation factor1 expression (NeuroD1). In addition, Vitamin D3 significantly alleviated anxiety- and depressive-like behaviors in TST and EPM test, decreased GFAP expression level, modified hippocampal astrocyte activation pattern, and advanced brain-derived neurotrophic factor (BDNF) distribution and expression in CA1 and CA3 of the hippocampus. ConclusionsTaken together, our results suggest that, by inhibiting the over-activation of astrocytes and increasing BDNF and neuron protection, vitamin D treatment ameliorates coal-dust-induced depressive and anxiety-like behavior, which is the first evidence that vitamin D may be a new approach for treating mood disorders caused by particulate matter.

Anticonvulsant activity of Nymphaea lotus Linn. extract in mice: The role of GABAergic-glutamatergic neurotransmission and antioxidant defence mechanisms

Epilepsy remains an unmet medical need affecting more than 50 million people worldwide with about 125,000 mortality annually and more prevalent in low- and middle-income countries. Nymphaea lotus (also known as water lilly) is an aquatic plant used traditionally to treat convulsive episodes in Southwestern Nigeria. This study was undertaken to evaluate anticonvulsant activity of aqueous Nymphaea lotus extract (ANL) and ethanol Nymphaea lotus extract (ENL) on chemical-induced seizures in mice as well as possible mechanisms of action. Vehicle (10 mL/kg, p.o.), ANL (50–200 mg/kg, p.o.), ENL (50–200 mg/kg) or diazepam (5 mg/kg, p.o.) was administered 1 h prior to chemo-convulsant (picrotoxin (PCT), pentylenetetrazol (PTZ), strychnine or N-methyl-D-aspartate (NMDA)) administration. Most effective doses of the extracts were administered to mice after the establishment of temporal lobe epilepsy (TLE) induced by kainic acid. Thereafter, memory assessment in Y-maze, depressive-like behaviour in tail suspension test (TST) and anxiety model in elevated plus maze test (EPM). The prefrontal cortex and hippocampus were assayed for oxidative stress parameters. The pretreatment of mice with ANL or ENL significantly prolonged onset of seizures and reduced the duration of picrotoxin-, pentylenetetrazol-, and strychnine-induced seizures or NMDA-induced turning behaviour. Kainic acid induced spontaneous recurrent seizures and oxidative stress were ameliorated by N. lotus extracts. Moreover, N. lotus-induced anticonvulsant action was reversed by the pretreatment of mice with flumazenil (benzodiazepine receptor antagonist) or L-arginine (nitric oxide precursor). In addition, kainic acid induced neurodegeneration was reduced by N. lotus extract. Findings from this study showed anticonvulsant activity of Nymphaea lotus in neurotoxins-induced seizures through enhancement of inhibitory GABAergic/ antioxidant signalling and inhibition of glutamatergic neurotransmission

Antidepressant- and anxiolytic-like activities of Rosmarinus officinalis extract in rodent models: Involvement of oxytocinergic system

BackgroundOxytocin (OXT), a neuropeptide involved in mammal reproductive and prosocial behaviors, has been reported to interact with various stressor-provoked neurobiological changes, including neuroendocrine, neurotransmitter, and inflammatory processes. In view of disturbances in psychosocial relationships due to social isolation and physical distancing measures amid the COVID-19 pandemic, being one of the triggering factors for the recent rise in depression and anxiety, OXT is a potential candidate for a new antidepressant. MethodsIn this present study, we have aimed to investigate the effects of oral administration of Rosmarinus officinalis extract (RE), extracted from distillation residue of rosemary essential oil, on central OXT level in the context of other stress biomarkers and neurotransmitter levels in mice models. Tail suspension test (TST) and elevated plus maze test (EPMT) following LPS injection were employed to assess depressive- and anxiety-like behavior in mice, respectively. FindingsPretreatment with RE for seven days significantly improved behavior in TST and EPMT. Whole-genome microarray analysis reveals that RE significantly reversed TST stress-induced alterations in gene expressions related to oxytocinergic and neurotransmitter pathways and inflammatory processes. In both models, RE significantly increased central Oxt and Oxtr expressions, as well as OXT protein levels. RE also significantly attenuated stress-induced changes in serum corticosterone, brain and serum BDNF levels, and brain neurotransmitters levels in both models. InterpretationAltogether, our study is the first to report antidepressant- and anxiolytic-like activities of RE through modulating oxytocinergic system in mice brain and thus highlights the prospects of RE in the treatment of depressive disorders of psychosocial nature.

Liver hydrolysate improves depressive-like behavior in olfactory bulbectomized mice: Involvement of hippocampal neurogenesis through the AMPK/BDNF/CREB pathway

Recently, we has reported that AMPK activator has antidepressant effect. Previous our study suggested that liver hydrolysate (LH) activated adenosine monophosphate-activated protein kinase (AMPK) in periphery. However, the effect of LH on depression is unclear. Therefore, we examines whether LH has antidepressant effect on olfactory bulbectomized (OBX) mice. OBX mice showed depressive-like behavior in tail-suspension test and reduction of hippocampal neurogenesis, while these changes were reversed by LH. LH enhanced hippocampal phosphate-AMPK, brain-derived neurotrophic factor (BDNF) and phosphate-cyclic adenosine monophosphate response element-binding protein (CREB) in OBX mice. These data indicate that LH may produce antidepressant effects via hippocampal AMPK/BDNF/CREB signaling.

Fabrication of solid lipid nanoparticles containing vitexin protects dopaminergic neurons against 6-hydroxydopamine induced Parkinson's disease model via altered the genetic backgrounds

Vitexin is a flavonoid which obtained from Crataegus pinnatifida Bunge. Further, its neuroprotective effects are examined in PD model. The motive of the current study was to fabricate vitexin loaded solid lipid nanoparticles and evaluate the effect against 6- hidroxidopamine (6-OHDA) induced parkinson's disease animal model. Intracerebroventricular injection of 6-OHDA was used for induction the PD and mice were treated with the said drug loaded nanocarrier for 28 days. In our study, hot melt emulsification and ultrasonication method was employed for the preparation of Vitexin loaded nanolipoidal carrier. Further, the enzymatic activities incudes Catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) glutathione peroxidase (GPx), glutathione S-transferase (GST), level of reactive oxygen species, total reactive antioxidant dopamine and its metabolite homovanilic and 3, 4-dihydroxyphenylacetic acid, were determined in the striatum. Furthermore, the behavioural parameters including locomotor, memory and depressive were estimated. The Vitexin loaded solid lipid nanoparticles therapeutics in 6-OHDA induced Parkinson's, results clearly showed improvement in total reactive antioxidant, CAT, GPx, Dopamine and its metabolite level in striatum of mice. We also observed that reactive oxygen species in the striatum were diminished by solid lipid nanoparticles of Vitexin. Furthermore, the said formulation is well efficient in averting the memory destruction in Morris water maze test as well as depressive like behaviour in tail suspension test. Vitexin loaded solid lipid nanoparticles founds protective effects in neurodegeneration on 6-OHDA induced neurotoxicity in mice. In features, this could be alternative effective therapeutic approach for the management of PD.

Chronic high dose of captopril induces depressive-like behaviors in mice: possible mechanism of regulatory T cell in depression.

Major depression has various types of symptoms and disease courses with inconsistent response to monoamine-related antidepressants. Thus, monoamine theory may not be the only pathophysiologic pathway relevant to depression. Recently, it has been suggested that regulatory T cell (Treg) is associated with depression. Based on our previous study that showed decreased regulatory T cell (Treg) population following chronic high-dose captopril (CHC, 40 mg/kg/day * 21 days) administration, we examined whether CHC alone can induce depressive-like behaviors in mice even without stressful stimuli. In this study, we found that CHC induced depressive-like behaviors in tail suspension test (TST) and forced swimming test (FST) without systemic illness, while it did not induce anhedonic behavior, anxiety-like behaviors, or sociality-related behavior. The depressive-like behaviors were rescued by either CHC washout or antidepressant. CHC caused reduction in foxp3 and gata3 mRNA expression in the lymph nodes with elevation in plasma IL-1β and IL-6. Interestingly, CHC increased serum angiotensin II level. In the hippocampus, CHC increased TNF-α and IL-6 mRNA expression with microglia activation while reduced glucocorticoid receptor expression. However, CHC did not affect to hippocampal kynurenine pathway, serotonin level, hypothalamic corticotropin-releasing hormone mRNA level, or serum corticosterone level. Consequently, we propose that CHC may induce a specific form of depressive-like behaviors via Treg reduction and microglial activation.

Developmental Neurotoxic Effects of Percutaneous Drug Delivery: Behavior and Neurochemical Studies in C57BL/6 Mice.

Dermatosis often as a chronic disease requires effective long-term treatment; a comprehensive evaluation of mental health of dermatology drug does not receive enough attention. An interaction between dermatology and psychiatry has been increasingly described. Substantial evidence has accumulated that psychological stress can be associated with pigmentation, endocrine and immune systems in skin to create the optimal responses against pathogens and other physicochemical stressors to maintain or restore internal homeostasis. Additionally, given the common ectodermal origin shared by the brain and skin, we are interested in assessing how disruption of skin systems (pigmentary, endocrine and immune systems) may play a key role in brain functions. Thus, we selected three drugs (hydroquinone, isotretinoin, tacrolimus) with percutaneous excessive delivery to respectively intervene in these systems and then evaluate the potential neurotoxic effects. Firstly, C57BL/6 mice were administrated a dermal dose of hydroquinone cream, isotretinoin gel or tacrolimus ointment (2%, 0.05%, 0.1%, respectively, 5 times of the clinical dose). Behavioral testing was performed and levels of proteins were measured in the hippocampus. It was found that mice treated with isotretinoin or tacrolimus, presented a lower activity in open-field test and obvious depressive-like behavior in tail suspension test. Besides, they damaged cytoarchitecture, reduced the level of 5-HT-5-HT1A/1B system and increased the expression of apoptosis-related proteins in the hippocampus. To enable sensitive monitoring the dose-response characteristics of the consecutive neurobehavioral disorders, mice received gradient concentrations of hydroquinone (2%, 4%, 6%). Subsequently, hydroquinone induced behavioral disorders and hippocampal dysfunction in a dose-dependent response. When doses were high as 6% which was 3 times higher than 2% dose, then 100% of mice exhibited depressive-like behavior. Certainly, 6% hydroquinone exposure elicited the most serious impairment of hippocampal structure and survival. The fact that higher doses of hydroquinone are associated with a greater risk of depression is further indication that hydroquinone is responsible for the development of depression. These above data demonstrated that chronic administration of different dermatology drugs contributed into common mental distress. This surprising discovery of chemical stressors stimulating the hippocampal dysfunction, paves the way for exciting areas of study on the cross-talk between the skin and the brain, as well as is suggesting how to develop effective and safe usage of dermatological drugs in daily practice.

Magnolol Enhances Hippocampal Neurogenesis and Exerts Antidepressant-Like Effects in Olfactory Bulbectomized Mice.

Magnolol is the main constituent of Magnolia bark and has been reported to exhibit antidepressant effects in rodent models. Hippocampal neurogenesis and neurotrophins such as brain-derived neurotrophic factor are integrally involved in the action of conventional antidepressants. Here, we investigated the effects of magnolol on depressive behaviours, impaired hippocampal neurogenesis and neurotrophin-related signal transduction in an olfactory bulbectomy (OBX) mouse model of depression. Mice were submitted to OBX to induce depressive behaviour, which was evaluated in the tail suspension test. Magnolol was administered orally by gavage needle. Neurogenesis was assessed by analysis of cells expressing NeuN, a neuronal marker, and 5-bromo-2'-deoxyuridine (BrdU) uptake. Phosphorylation levels of protein kinase B (Akt), extracellular signal-regulated kinase and cyclic AMP-responsive element-binding protein were evaluated by Western blot. Fourteen day treatment with magnolol (50 or 100 mg/kg/day) significantly improved OBX-induced depressive behaviour in tail suspension test. In agreement, magnolol significantly rescued impairments of hippocampal neurogenesis. Moreover, single treatments with magnolol (50 mg/kg) significantly increased phosphorylation of Akt, extracellular signal-regulated kinase and cyclic AMP-responsive element-binding protein after 3 h. The present data indicate that magnolol exerts antidepressant-like effects on behaviours by enhancing hippocampal neurogenesis and neurotrophin-related intracellular signalling in OBX mice. Copyright © 2016 John Wiley & Sons, Ltd.

Involvement of norepinephrine and serotonin system in antidepressant-like effects of oleoylethanolamide in the mice models of behavior despair

Oleoylethanolamide (OEA) is an endocannabinoid analogy that belongs to a family of endogenous acylethanolamides. Increasing evidence suggests that OEA may act as an endogenous neuroprotective factor and participate in the control of mental disorder-related behaviors. In the present study, we investigated the antidepressant- like potential of OEA in mice in comparison with clomipramine (Cp). 50 mice were randomly divided into 5 groups, and treated with a vehicle (0.3% methyl cellulose, 20mL/kg, p.o.), OEA (2.5, 5–10mg/kg, p.o.), or Cp (10mg/kg, p.o.) for 7 days. The immobility was used to evaluate depressive-like behaviors in tail suspension test (TST) and forced swimming test (FST). ELISA detected changes in cerebral noradrenaline (NE) and serotonin (5-HT) levels. Likewise, in the drug-induced model of depression, OEA was given once daily at 10mg/kg (p.o.) for 7 consecutive days. Then, the mice received reserpine (4mg/kg, i.p.) and the rectal temperature was measured at different time points. Consequently, head twitch behavior induced by intraperitoneal injection of 5-hydroxy-tryptophan (5-HTP; 300mg/kg) were determined. The experimental data showed that OEA (2.5–10mg/kg) treatment significantly decreased the immobility as compared to the control group, and OEA (10mg/kg) treatment significantly increased 5-HTP-induced head twitch behavior and reversed reserpine-induced hypothermia and increased cerebral levels of NE and 5-HT. Thus, the antidepressant effects of OEA may be related to regulating central monoamine neurotransmitters.

Chronic treatment with mood-stabilizers attenuates abnormal hyperlocomotion of GluA1-subunit deficient mice.

Abnormal excitatory glutamate neurotransmission and plasticity have been implicated in schizophrenia and affective disorders. Gria1−/− mice lacking GluA1 subunit (encoded by Gria1 gene) of AMPA-type glutamate receptor show robust novelty-induced hyperactivity, social deficits and heightened approach features, suggesting that they could be used to test for anti-manic activity of drugs. Here, we tested the efficacy of chronic treatment with established anti-manic drugs on behavioural properties of the Gria1−/− mice. The mice received standard mood stabilizers (lithium and valproate) and novel ones (topiramate and lamotrigine, used more as anticonvulsants) as supplements in rodent chow for at least 4 weeks. All drugs attenuated novelty-induced locomotor hyperactivity of the Gria1−/− mice, especially by promoting the habituation, while none of them attenuated 2-mg/kg amphetamine-induced hyperactivity as compared to control diet. Treatment with lithium and valproate reversed the elevated exploratory activity of Gria1−/− mice. Valproate treatment also reduced struggling behaviour in tail suspension test and restored reciprocally-initiated social contacts of Gria1−/− mice to the level shown by the wild-type Gria1+/+ mice. Gria1−/− mice consumed slightly more sucrose during intermittent sucrose exposure than the wild-types, but ran similar distances on running wheels. These behaviours were not consistently affected by lithium and valproate in the Gria1−/− mice. The efficacy of various anti-manic drug treatments on novelty-induced hyperactivity suggests that the Gria1−/− mouse line can be utilized in screening for new therapeutics.

Etazolate rescues behavioral deficits in chronic unpredictable mild stress model: Modulation of hypothalamic–pituitary–adrenal axis activity and brain-derived neurotrophic factor level

Preliminary study in our laboratory showed that etazolate produced antidepressant- and anxiolytic-like effects in rodent models, however, the ability of etazolate to produce antidepressant- and anxiolytic-like effects and underlying mechanism(s) in chronic unpredictable mild stress (CUMS) model have not been adequately addressed. This study was aimed to investigate the beneficial effects of etazolate on CUMS-induced behavioral deficits (depression- and anxiety-like behaviors). In addition, the possible underlying mechanism(s) of etazolate in CUMS model was also investigated by measuring serum corticosterone (CORT) and brain-derived neurotrophic factor (BDNF) levels. Mice were subjected to a battery of stressors for 28days. Etazolate (0.5 and 1mg/kg, p.o.) and fluoxetine (20mg/kg, p.o.) were administered during the last 21days (8–28th) of the CUMS paradigm. The results showed that 4-weeks CUMS produces significant depression-like behavior in tail suspension test (TST) and partial anxiety-like behavior in elevated plus maze (EPM) and open field test (OFT). Stressed mice have also shown a significant high serum CORT and low BDNF level. Chronic treatment with etazolate (0.5 and 1mg/kg., p.o.) and fluoxetine (20mg/kg., p.o.) produced significant antidepressant-like behavior in TST (decreased duration of immobility), whereas, partial anxiolytic-like behavior in EPM (increased percentage of open arm entries) and OFT (increased % central ambulation score, total ambulation score and time spent in center zone). In addition, etazolate and fluoxetine treatment significantly (p<0.05) increased the BDNF level and inhibited the hypothalamic–pituitary–adrenocortical (HPA) axis hyperactivity, as evidenced by low serum CORT level in stressed mice. In addition, etazolate and fluoxetine also showed significant antidepressant- and anxiolytic-like effects in normal control mice. In this study no significant changes were observed in locomotor activity in actophotometer test. Moreover, we did not find any effect of etazolate and fluoxetine on CORT and BDNF levels in normal control mice. In conclusion, the results of the present study suggested compelling evidences that etazolate has more marked effect on depression-like behavior in mice, which is atleast in part may be related to their modulating effects on the HPA axis and BDNF level.

Depression-like behavior in subclinical hypothyroidism rat induced by hemi-thyroid electrocauterization

The purpose of this study was to investigate the depression-like behavior performances of subclinical hypothyroidism (SCH) rat. SCH rat model was induced by hemi-thyroid electrocauterization, and the behavior performances were measured by sucrose preference test, force swimming test (FST), and tail suspension test (TST). SCH rat model was established successfully by hemi-thyroid electrocauterization. In the behavior tasks, SCH rats displayed depression-like behavior were indicated as a significant elevation of immobility time in both the TST and FST, though the sucrose preference was not significantly decreased. The index of left adrenal cortex in both SCH and clinical hypothyroidism (CH) group significantly increased, and many large lipid vacuoles were observed in the zona fasciculata cells. The serum corticosterone concentration and hypothalamic corticotropin-releasing hormone mRNA expression 2 h after behavior test was markedly up-regulated in CH rats, but not SCH rats, indicated that SCH induced a less impairment of HPA axis than CH did. The important finding of this study was that the concentration of hippocampal T3 was lower in SCH group than that of the sham group. Furthermore, the results of Pearson correlation test showed that the immobility behaviors in TST and FST were both negatively correlated with hippocampal T3 concentration. Taking together, our results indicated that SCH could result in depression-like behavior, accompanied with subtle hyperactivity of HPA axis. The reduced hippocampal T3 prior to the reduction of thyroid hormone in serum might be taken as an early sign of hippocampus impairment in the progression from SCH to CH.

Alcohol reverses depressive and pronociceptive effects of chronic stress in mice with enhanced activity of the opioid system.

The role of the opioid system in mediating effects of alcoholism and stress in depression is far from clear. We studied, therefore, the effects of chronic mild stress (CMS) and alcohol drinking on depression-like behavior and nociception in lines of mice selected for high (HA) or low (LA) swim stress-induced analgesia. Compared to the LA mice, the HA animals display up-regulation of opioid receptor system function and depression-like behavior in tail suspension test (TST). We report now that alcohol reverses depressive and pronociceptive effect of CMS in HA mice. In contrast, in LA mice CMS does not affect nociception or behavior in TST and the animals are not susceptible to alcohol under CMS. The results suggest that opioid system activity may determine the effects of alcohol on behavior under stress and, therefore, link predispositions to depression and to alcoholism.

Effects of histamine H 1 receptor antagonists on depressive-like behavior in diabetic mice

We previously reported that streptozotocin-induced diabetic mice showed depressive-like behavior in the tail suspension test. It is well known that the central histaminergic system regulates many physiological functions including emotional behaviors. In this study, we examined the role of the central histaminergic system in the diabetes-induced depressive-like behavior in the mouse tail suspension test. The histamine contents in the hypothalamus were significantly higher in diabetic mice than in non-diabetic mice. The histamine H 1 receptor antagonist chlorpheniramine (1–10 mg/kg, s.c.) dose-dependently and significantly reduced the duration of immobility in both non-diabetic and diabetic mice. In contrast, the selective histamine H 1 receptor antagonists epinastine (0.03–0.3 μg/mouse, i.c.v.) and cetirizine (0.01–0.1 μg/mouse, i.c.v.) dose-dependently and significantly suppressed the duration of immobility in diabetic mice, but not in non-diabetic mice. Spontaneous locomotor activity was not affected by histamine H 1 receptor antagonists in either non-diabetic or diabetic mice. In addition, the number and affinity of histamine H 1 receptors in the frontal cortex were not affected by diabetes. In conclusion, we suggest that the altered neuronal system mediated by the activation of histamine H 1 receptors is involved, at least in part, in the depressive-like behavior seen in diabetic mice.