Depressive Behavior In Rats Research Articles

Interleukin-6: Its role and mechanisms in rescuing depression-like behaviors in rat models of depression

Neuronal injury within specific brain regions is considered a critical risk factor in the pathophysiology of depression. However, the underlying mechanisms of this process, and thus the potential for development of novel therapeutic strategies in the treatment of depression, remain largely unknown. Here, we report that Il-6 protects against neuronal anomalies related with depression, in part, by suppressing oxidative stress and consequent autophagic and apoptotic hyperactivity. Specifically, we show that IL-6 is downregulated within the CA1 hippocampus in two animal models of depression and upregulated by antidepressants. Increasing levels of IL-6 in the CA1 region result in pleiotropic protective actions including reductions in oxidative stress and modulation of autophagy, anti-immuno-inflammatory activation and anti-apoptotic effects in CA1 neurons, all of which are associated with the rescue of depression-like behaviors. In contrast, IL-6 downregulation exacerbates neuronal anomalies within the CA1 region and facilitates the genesis of depression phenotypes in rats. Interestingly, in addition to attenuating oxidative damage, the antioxidant, N-acetylcysteine (NAC), is also associated with significantly decreased neuronal deficits and the display of depressive behaviors in rats. These results suggest that IL-6 may exert neuroprotection within CA1 neurons via pleiotropic mechanisms and may serve as a potential therapeutic target for the treatment of depression.

Dynamic monitoring of depressive behavior induced by nonylphenol and its effect on synaptic plasticity in rats

The etiology of depression is not known, it is thought that endocrine-disrupting chemicals (EDCs) contribute to the disease. Results of our previous research have shown that nonylphenol (NP), a well-known EDC, has neurotoxic effects, however, whether NP can induce depressive behavior by affecting synaptic plasticity has not yet been clearly elucidated. The depressive behavior induced by subchronic exposure to NP and its effect on the neuronal synaptic plasticity in rats are dynamically observed. Thirty Sprague-Dawley rats were randomly divided into 3 groups: control group (C, corn oil), NP group (NP, 4 mg/kg), and depression model group (D, corticosterone 20 mg/kg). There were 8 rats in each group. The depressive behavior of rats was tested by sucrose preference test, open-field test, and forced swimming test once a month for 3 months. The serum levels of brain-derived neurotrophic factor (BDNF) and corticosterone were detected by ELISA assay, and cellular morphological changes were observed by hematoxylin-eosin (HE) staining. The number of nerve cells, the length of dendrites, and the density of dendritic spines were observed by Golgi staining, and the synaptic cleft width, the postsynaptic density (PSD) thickness, and the synaptic interface curvature were observed by transmission electron microscope. Compared with the control group, the consumption of sucrose solution decreased in the NP group at the 2nd and 3rd month compared to the 1st month (F = 9.887, P = 0.002). The number of central square entries, the central square duration, and the total distance of movement were all decreased, and the decreasing degrees at the 3rd month were greater than those at the 1st month (F = 21.191, P < 0.001; F = 9.836, P = 0.002). The time of immobility for the NP group at the 1st month was higher than that in the control group (F = 6.912, P = 0.002). The expression of BDNF in the NP-treated group was higher than the control, while the expression of corticosterone in the NP-treated group was lower than the control. In the NP group, the cytoplasm of nerve cells contracted and appeared disordered. The neuron arrangement was disordered, and the number of cells, the length of the apex, the length of the basal dendrites, and the dendritic spine density were all lower in the NP group than those in the control group. The PSD thickness, the synaptic cleft width, and synaptic interface curvatures were all decreased in the NP group when compared to the control group. Subchronic exposure to 4 mg/kg NP led to depressive behavior in rats, and the depressive behavior and alterations in synaptic plasticity were more obvious with longer exposure time.

Brain-Derived Neurotrophic Factor Precursor in the Hippocampus Regulates Both Depressive and Anxiety-Like Behaviors in Rats.

Depression and anxiety are two affective disorders that greatly threaten the mental health of a large population worldwide. Previous studies have shown that brain-derived neurotrophic factor precursor (proBDNF) is involved in the development of depression. However, it is still elusive whether proBDNF is involved in anxiety, and if so, which brain regions of proBDNF regulate these two affective disorders. The present study aims to investigate the role of proBDNF in the hippocampus in the development of depression and anxiety. Rat models of an anxiety-like phenotype and depression-like phenotype were established by complete Freund's adjuvant intra-plantar injection and chronic restraint stress, respectively. Both rat models developed anxiety-like behaviors as determined by the open field test and elevated plus maze test. However, only rats with depression-like phenotype displayed the lower sucrose consumption in the sucrose preference test and a longer immobility time in the forced swimming test. Sholl analysis showed that the dendritic arborization of granule cells in the hippocampus was decreased in rats with depression-like phenotype but was not changed in rats with anxiety-like phenotype. In addition, synaptophysin was downregulated in the rats with depression-like phenotype but upregulated in the rats with anxiety-like phenotype. In both models, proBDNF was greatly increased in the hippocampus. Intra-hippocampal injection anti-proBDNF antibody greatly ameliorated the anxiety-like and depressive behaviors in the rats. These findings suggest that despite some behavioral and morphological differences between depression and anxiety, hippocampal proBDNF is a common mediator to regulate these two mental disorders.

Studies of the effect of cerebroprotective substances on the course of stress-induced behavioral depression

Introduction. Atrophic disturbances of neurons of the limbic structures of the brain, which lead to insufficient regulation of emotions and mood, cause depression. Substances with cerebroprotective activity have the ability to inhibit further development and even reverse atrophic damage to neurons.&#x0D; Materials and methods. Using electrophysiological techniques, the cerebroprotective activity of piracetam, diacamf – (±)-cis-3-(2-benzimidazolyl)-1,2,2-trimethylcyclopentanone-carboxylic acid hydrochloride and the compound R-86, or 3,2’-spiro-pyrrolo-2-oxindole, was investigated in rat hippocampal slices. In behavioral experiments, there was studied the influence of the above substances, which had been administered for 20 days, on the most important manifestations of behavioral depression in rats caused by a five-day swim stress, such as the time of immobilization in the forced swim test and the indicator of preference for consuming sucrose solution. In addition, the influence of piracetam and diacamf was studied on the effects of the classic antidepressant imipramine.&#x0D; Results and discussion. It was found that piracetam, diacamf and the compound R-86 in in vitro studies reduced the damage to the pyramidal hippocampal neurons caused by anoxia and aglycemia, the excitotoxic activity of N-methyl-D-aspartate and oxidative stress when hydrogen peroxide was applied to the slices. Cerebroprotective activity of the test substances, when they are systemically administered for 20 days, is linked with their antidepressant-like effect, which was manifested in a decrease in the immobilization time in the swim test and an increase in the sucrose solution consumption indicator. Co-administration of piracetam in rats potentiated antidepressant activity of imipramine, and diacamf showed additive synergism with the antidepressant.&#x0D; Conclusion. Substances with cerebroprotective activity in their chronic administration may show an antidepressant-like effect. Those that potentiate the action of classical anidepressants can be used in conjunction with antidepressants during episodes of exacerbation of the disease. Less active cerebroprotective drugs can be recommended during remission for its prolongation.

Different behavioral and pathological changes between epilepsy-associated depression and primary depression models

PurposeComorbid depression is common in patients with epilepsy. However, the epilepsy-associated depression is generally atypical and has not been fully recognized by neurologists. This study aimed to compare the behavioral and pathological changes between the chronic lithium chloride-pilocarpine rat epilepsy model (Licl-pilocarpine model) and the Chronic Unpredictable Mild Stress rat depression model (CUMS model), to evaluate for differences between epilepsy-associated depression and primary depression. MethodsThe Licl-pilocarpine model and the CUMS model were established respectively and simultaneously. Spontaneous seizures were recorded by video monitoring. Forced swim test (FST) and sucrose consumption test (SCT) were performed to test depressive behaviors. Immobility time (IMT) and climbing time (CMT) in FST, sucrose preference rate (SPR) in SCT, and weight gain rate (WGR) were adopted to represent severity of depressive behaviors in rats. Immunofluorescent staining was conducted to measure expressions of neuronal specific nuclear protein (NeuN), glial fibrillary acidic protein (GFAP), and cluster of differentiation molecule 11b (CD11b) in the hippocampus of Licl-pilocarpine model, CUMS model, and Control group. ResultsSignificantly, more prolonged IMT was observed in both the Licl-pilocarpine model (p<0.05) and the CUMS model (p<0.01) than Control group. But decreased WGR was only seen in the CUMS model. The percentage of rats with CMT greater than 100s was significantly higher in the Licl-pilocarpine model than the CUMS model (p<0.05). Increased CMT was observed in the Licl-pilocarpine model with mild depression subgroup (EMD, IMT≤100s) even compared with the Control group. Neuronal loss was both found in the Licl-pilocarpine model and the CUMS model when comparing with the Control group (p<0.05). However, the number of GFAP and CD11b staining cells was both greater in the Licl-pilocarpine model than the CUMS model and the Control group (p<0.05). ConclusionThere were some different depressive behavioral and hippocampal pathological changes between the Licl-pilocarpine and the CUMS models except for some common features. Gliosis and microglial activation might be more involved in the pathophysiology of epilepsy-associated depression than primary depression.

Saikosaponin D relieves unpredictable chronic mild stress induced depressive-like behavior in rats: involvement of HPA axis and hippocampal neurogenesis.

Saikosaponin D (SSD), a major bioactive component isolated from Radix Bupleuri, has been reported to exert neuroprotective properties. The present study was designed to investigate the anti-depressant-like effects and the potential mechanisms of SSD. Behavioural tests including sucrose preference test (SPT), open field test (OFT) and forced swim test (FST) were performed to study the antidepressant-like effects of SSD. In addition, we examined corticosterone and glucocorticoid receptor (GR) levels to evaluate hypothalamic-pituitary-adrenal (HPA) axis function. Furthermore, hippocampal neurogenesis was assessed by testing doublecortin (DCX) levels, and neurotrophic molecule levels were also investigated in the hippocampus of rats. We found that unpredictable chronic mild stress (UCMS) rats displayed lost body weight, decreased sucrose consumption in SPT, reduced locomotive activity in OFT, and increased immobility time in FST. Chronic treatment with SSD (0.75, 1.50mg/kg) remarkably ameliorated the behavioral deficiency induced by UCMS procedure. SSD administration downregulated elevated serum corticosterone levels, as well as alleviated the suppression of GR expression and nuclear translocation caused by UCMS, suggesting that SSD is able to remit the dysfunction of HPA axis. In addition, Western blot and immunohistochemistry analysis showed that SSD treatment significantly increased the generation of neurons in the hippocampus of UCMS rats indicated by elevated DCX levels. Moreover, hippocampal neurotrophic molecule levels of UCMS rats such as phosphorylated cAMP response element binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) were raised after SSD treatment. Together, Our results suggest that SSD opposed UCMS-induced depressive behaviors in rats, which was mediated, partially, by the enhancement of HPA axis function and consolidation of hippocampal neurogenesis.

Silymarin ameliorates experimentally induced depressive like behavior in rats: Involvement of hippocampal BDNF signaling, inflammatory cytokines and oxidative stress response

Silymarin is a polyphenolic flavonoid of Silybum marianum, exhibited neuroprotection and antidepressant like activity in acute restraint stressed mice. The main objective of the present study is to investigate possible antidepressant like activity of silymarin in experimentally induced depressive behavior in rats. The depressive behaviors were induced in rats by olfactory bulbectomized (OBX) technique. Wistar rats were administered with silymarin at a dose of 100mg/kg and 200mg/kg, by per oral in OBX and sham operated rats. Behavioral (ambulatory and rearing activity and immobility time), neurochemical [serotonin (5-HT), dopamine (DA), norepinephrine (NE) and brain derived neurotrophic factor (BDNF) level], biochemical (MDA formation, IL-6, TNF-α and antioxidants) changes in hippocampus and cerebral cortex along with serum corticosterone were investigated. Rats subjected to OBX elicited significant increase in immobility time, ambulatory and rearing behaviors, reduced BDNF level, 5-HT, DA, NE and antioxidant parameters along with increased serum corticosterone, MDA formation, IL-6, and TNF-α in hippocampus and cerebral cortex compared to sham operated rats. Administration of with silymarin significantly attenuated immobility time, ambulatory and rearing behaviors, serum corticosterone and improved BDNF expression, 5-HT, DA, NE and antioxidant paradigms in cerebral cortex as well as hippocampus. In addition, silymarin attenuated IL-6, and TNF-α significantly in hippocampus and cerebral cortex in OBX rats. Thus, silymarin exhibits anti-depressant-like activity in OBX rats due to alterations in several neurotransmitters, endocrine and immunologic systems, including BDNF, 5-HT, DA, NE, MDA formation, IL-6, and TNF-α in hippocampus and cerebral cortex as well as serum corticosterone.

The impact of chronic mild stress on long-term depressive behavior in rats which have survived sepsis

The present study was created to investigate the effects of chronic mild stress (CMS) on the depressive behavior and neurochemical parameters of rats that were subjected to sepsis. Wistar rats were subjected to a CMS protocol, and sepsis was induced by cecal ligation and perforation (CLP). The animals were then divided into 4 separate groups; Control + Sham (n = 20), Control + CLP (n = 30), CMS + Sham (n = 20) and CMS + CLP (n = 30). Body weight, food and water intake and mortality were measured on a daily basis for a period of 10 days after the induction of sepsis. Locomotor activity, splash and forced swimming tests were performed ten days after CLP. At the end of the test period, the animals were euthanized, and the prefrontal cortex and hippocampus were removed to determine the levels of cytokines and oxidative damage. Our results show that there was no significant interaction between CMS and CLP in relation to locomotor activity and the forced swimming test. However, we did observe a significant decrease in total grooming time in the Control + CLP and CMS + Sham groups, with the CMS + CLP group showing behavior similar to that of the control animals. This was found to be related to a decrease in the levels of brain cytokines, and not to oxidative damage parameters. Collectively, our results suggest that a previous stress caused by CMS can protect the brain against the systemic acute and severe stress elicited by sepsis.

5-HT in the dorsal raphe nucleus is involved in the effects of 100-Hz electro-acupuncture on the pain-depression dyad in rats.

The pain-depression dyad is becoming widespread in the clinic and is attracting increasing attention. A previous study by our group found that 100-Hz electro-acupuncture (EA), but not 2-, 50- and 2/100-Hz EA, was effective against the reserpine-induced pain-depression dyad. This finding is in contrast to the fact that low-frequency EA is commonly used to treat supraspinal-originating diseases. The present study aimed to investigate the mechanism underlying the effects of 100-Hz EA on the pain-depression dyad. Repeated reserpine injection was found to induce allodynia and depressive behaviors in rats. It decreased 5-hydroxytryptamine (5-HT) levels and immunoreactive expressions in the dorsal raphe nucleus (DRN). 100-Hz EA alleviated the pain-depression dyad and upregulated 5-HT in the DRN of reserpine-injected rats. Intracerebroventricular injection of para-chlorophenylalanine, an inhibitor of 5-HT resynthesis, suppressed the upregulation of 5-HT in the DRN by 100-Hz EA and partially counteracted the analgesic and anti-depressive effects of 100-Hz EA. The present study was the first to demonstrate that 5-HT in the DRN is involved in mediating the analgesic and anti-depressive effects of 100-Hz EA on the pain-depression dyad. This finding provided a scientific basis for high-frequency EA as a potential treatment for the pain-depression dyad.

Mo1945 - Short-Term Food Intake, Intestinal Transit and Depressive Behavior of Rats with Sleeve Gastrectomy are Independent of Ovarian Hormonal Status

Mo1945 - Short-Term Food Intake, Intestinal Transit and Depressive Behavior of Rats with Sleeve Gastrectomy are Independent of Ovarian Hormonal Status

Decreased Glycogen Content Might Contribute to Chronic Stress-Induced Atrophy of Hippocampal Astrocyte volume and Depression-like Behavior in Rats

The involvement of brain glycogen in the progress of chronic stress-induced impairment of hippocampal astrocyte structural plasticity and depression-like behavior is yet to be clarified. The present study designed three experiments to determine the role of brain glycogen in the plasticity and behavioral consequences of chronic stress. Time course studies on brain glycogen, astrocytes, and behavioral responses to stress were conducted in Experiment 1. Chronic stress decreased the hippocampal glycogen levels, reduced astrocytic size and protrusion length in the hippocampus, and induced depression-like behavior. Glycogen synthase 1 mRNA in the hippocampus was silenced by lentiviral vector-based RNA interference (RNAi) in Experiment 2. This RNAi produced a lack of glycogen in the hippocampus, decreased the hippocampal astrocyte size, and induced depressive behavior in rats. The mechanisms of chronic stress-induced brain glycogen decrease were investigated in Experiment 3. Chronic stress promoted hippocampal glycogen breakdown and increased hippocampal glycogen synthesis. Results suggest that decreased glycogen content was associated with chronic stress-induced atrophy of hippocampal astrocyte size and depression-like behavior. Furthermore, the decrease of glycogen content in the hippocampus might be due to the compensation of glycogen synthesis for breakdown in an insufficient manner.

Stress induces equivalent remodeling of hippocampal spine synapses in a simulated postpartum environment and in a female rat model of major depression

Stress and withdrawal of female reproductive hormones are known risk factors of postpartum depression. Although both of these factors are capable of powerfully modulating neuronal plasticity, there is no direct electron microscopic evidence of hippocampal spine synapse remodeling in postpartum depression. To address this issue, hormonal conditions of pregnancy and postpartum period were simulated in ovariectomized adult female Sprague–Dawley rats (n=76). The number of hippocampal spine synapses and the depressive behavior of rats in an active escape task were investigated in untreated control, hormone-withdrawn ‘postpartum’, simulated proestrus, and hormone-treated ‘postpartum’ animals. After ‘postpartum’ withdrawal of gonadal steroids, inescapable stress caused a loss of hippocampal spine synapses, which was related to poor escape performance in hormone-withdrawn ‘postpartum’ females. These responses were equivalent with the changes observed in untreated controls that is an established animal model of major depression. Maintaining proestrus levels of ovarian hormones during ‘postpartum’ stress exposure did not affect synaptic and behavioral responses to inescapable stress in simulated proestrus animals. By contrast, maintaining pregnancy levels of estradiol and progesterone during ‘postpartum’ stress exposure completely prevented the stress-induced loss of hippocampal spine synapses, which was associated with improved escape performance in hormone-treated ‘postpartum’ females. This protective effect appears to be mediated by a muted stress response as measured by serum corticosterone concentrations. In line with our emerging ‘synaptogenic hypothesis’ of depression, the loss of hippocampal spine synapses may be a novel perspective both in the pathomechanism and in the clinical management of postpartum affective illness.

Neuroprotective, Neurotrophic and Anti-oxidative Role of Bacopa monnieri on CUS Induced Model of Depression in Rat.

Major depression is a life threatening neuropsychiatric disorder that produces mental illness and major cause of morbidity. The present study was conducted to evaluate the neuroprotective, neurotrophic and antioxidant potential of Bacopa monnieri extract (BME) on chronic unpredictable stress (CUS) induced behavioral depression in rats. Behavioral tests were carried out for investigation of antidepressant like effects of BME, and potential mechanism was assessed by determining neurotrophin level and hippocampal neurogenesis. Depressive-like behavior was assessed by shuttle-box escape test, forced swim test and tail suspension test. Effect of BME on hypothalamic-pituitary-adrenal (HPA) axis was evaluated by measuring the plasma level of adrenocorticotropic hormone (ACTH) and corticosterone. The expression of brain derived neurotrophic factor (BDNF), neuronal marker doublecortin (DCX) in the hippocampus were measured and hippocampal neurogenesis was investigated by 5-bromo-2-deoxyuridine/neuronal nuclei (BrdU/NeuN). In addition, effects of BME on oxidative stress markers were also measured in the hippocampus of CUS exposed rats. The results indicated that BME significantly able to attenuate the depressive-like behaviors, normalized the levels of ACTH, corticosterone, and up-regulate the expression of BDNF, DCX and BrdU/NeuN in CUS induced rats compared to BME treated rats. It is also found that BME significantly increased the activity of antioxidant enzymes on CUS induced rats. These findings revealed that BME exerted neuroprotective effects possibly by promoting hippocampal neurogenesis with elevation of BDNF level and antioxidant defense against oxidative stress.

High Fat Diet-Induced Obesity Stimulate Depressive Behavior in Rats

High Fat Diet-Induced Obesity Stimulate Depressive Behavior in Rats

Administration of Ethanolic Extract of Ocimum Basilicum Leaves Attenuates Depression like Behavior in the Rats Sensitized by Ovalbumin

A relationship between inflammation and depression has been suggested. Ocimum basilicum, has been reported to have preventive effects of inflammatory responses. The aim of this study was to evaluate the effects of hydro-ethanolic extract of Ocimum basilicum leaves on depressive behaviors in rats sensitized by ovalbumin. The animals were grouped into: (1) Control: saline was injected, (2) Sensitized: sensitization was carried out by ovalbumin, (3-5) three groups including Sent-Ocim 50, Sent- Ocim 100 and Sent- Ocim 200 : sensitization was carried and also 50, 100 or 200 mg/kg, of Ocimum basilicum leave extract was injected. In open- field (O-F) test, the number of crossing in the central zone of the sensitized group was lower while, the number of crossing in the peripheral zone was higher than control (P<0. 05- P< 0.01). Treatment by 200 mg / kg of the extract increased the number of crossing in the central zone (P< 0.05). Furthermore, in the Sent-Ocim 50, Sent- Ocim 100 and Sent- Ocim 200 groups, the number of crossing in the peripheral zone was lower than that of the sensitized group(P< 0. 01- P< 0.001). In forced swimming (F-S) test, the immobility time in sensitized rats was higher while, the swimming and climbing times were lower than in the control ones (P< 0.05- P< 0. 001). The animals in Sent- Ocim 200 group had lower immobility while, higher swimming and climbing times compared to sensitized animals (P<0.01-P<0.001). The current study revealed that hydro-ethanolic extract of Ocimum basilicum leaves attenuates depressive behaviors in rats sensitized by ovalbumin. These results confirmed the benefits of Ocimum basilicum in the central nervous system.

Effects of nicotinic acetylcholine receptor agonists in assays of acute pain-stimulated and pain-depressed behaviors in rats.

Agonists at nicotinic acetylcholine receptors (nAChRs) constitute one drug class being evaluated as candidate analgesics. Previous preclinical studies have implicated α4β2 and α7 nAChRs as potential mediators of the antinociceptive effects of (–)-nicotine hydrogen tartrate (nicotine) and other nAChR agonists; however, these studies have relied exclusively on measures of pain-stimulated behavior, which can be defined as behaviors that increase in frequency, rate, or intensity after presentation of a noxious stimulus. Pain is also associated with depression of many behaviors, and drug effects can differ in assays of pain-stimulated versus pain-depressed behavior. Accordingly, this study compared the effects of nicotine, the selective α4/6β2 agonist 5-(123I)iodo-3-[2(S)-2-azetidinylmethoxy]pyridine (5-I-A-85380), and the selective α7 agonist N-(3R)-1-azabicyclo(2.2.2)oct-3-yl-4-chlorobenzamide in assays of pain-stimulated and pain-depressed behavior in male Sprague-Dawley rats. Intraperitoneal injection of dilute lactic acid served as an acute noxious stimulus to either stimulate a stretching response or depress the operant responding, which is maintained by electrical brain stimulation in an intracranial self-stimulation (ICSS) procedure. Nicotine produced a dose-dependent, time-dependent, and mecamylamine-reversible blockade of both acid-stimulated stretching and acid-induced depression of ICSS. 5-I-A-85380 also blocked both acid-stimulated stretching and acid-induced depression of ICSS, whereas N-(3R)-1-azabicyclo(2.2.2)oct-3-yl-4-chlorobenzamide produced no effect in either procedure. Both nicotine and 5-I-A-85380 were ≥10-fold more potent in blocking the acid-induced depression of ICSS than in blocking the acid-induced stimulation of stretching. These results suggest that stimulation of α4β2 and/or α6β2 nAChRs may be especially effective to alleviate the signs of pain-related behavioral depression in rats; however, nonselective behavioral effects may contribute to apparent antinociception.

Overexpression of human GATA-1 and GATA-2 interferes with spine formation and produces depressive behavior in rats.

Functional consequences to which vertebrate GATA transcription factors contribute in the adult brain remain largely an open question. The present study examines how human GATA-1 and GATA-2 (hGATA-1 and hGATA-2) are linked to neuronal differentiation and depressive behaviors in rats. We investigated the effects of adeno-associated viral expression of hGATA-1 and hGATA-2 (AAV-hGATA1 and AAV-hGATA2) in the dentate gyrus (DG) of the dorsal hippocampus on dendrite branching and spine number. We also examined the influence of AAV-hGATA1 and AAV-hGATA2 infusions into the dorsal hippocampus on rodent behavior in models of depression. Viral expression of hGATA-1 and hGATA-2 cDNA in rat hippocampal neurons impaired dendritic outgrowth and spine formation. Moreover, viral-mediated expression of hGATA-1 and hGATA-2 in the dorsal hippocampus caused depressive-like deficits in the forced swim test and learned helplessness models of depression, and decreased the expression of several synapse-related genes as well as spine number in hippocampal neurons. Conversely, shRNA knockdown of GATA-2 increased synapse-related gene expression, spine number, and dendrite branching. The results demonstrate that hGATA-1 and hGATA-2 expression in hippocampus is sufficient to cause depressive like behaviors that are associated with reduction in spine synapse density and expression of synapse-related genes.

Gender differences in CMS and the effects of antidepressant venlafaxine in rats

Gender differences in susceptibility to chronic mild stress (CMS) and effects of venlafaxine in rats have been investigated in the current study. Male and female SD rats were exposed to CMS or CMS plus chronic venlafaxine administration (10mg/kg, 21days) in order to study depressive behavior in rats. Rats were tested in open field test and sucrose preference test to figure out gender differences in behavior. Then serum corticosterone and the expression of FKBP5 in hippocampus of rats were detected to explore the possible mechanism. The results showed that the CMS impact on behavioral parameters and corticosterone levels and response to venlafaxine were gender dependent. Female rats appeared more vulnerable in the dysregulation of HPA axis to CMS. Venlafaxine treatment normalized depressive-like behavior in both gender. However, venlafaxine treated male rats exhibited better improved explore behavior and anhedonia. FKBP5 might be involved in the explanation of gender differences in CMS and venlafaxine treatment. Male and female rats respond differently to chronic stress and venlafaxine continuous treatment. This results have guiding meaning in design of trials related to stress induced depression.

Pain-Related Depression of the Mesolimbic Dopamine System in Rats: Expression, Blockade by Analgesics, and Role of Endogenous κ-opioids

Pain is often associated with depression of behavior and mood, and relief of pain-related depression is a common goal of treatment. This study tested the hypothesis that pain-related behavioral depression is mediated by activation of endogenous κ-opioid systems and subsequent depression of mesolimbic dopamine release. Adult male Sprague-Dawley rats were implanted with electrodes targeting the medial forebrain bundle (for behavior studies of intracranial self-stimulation (ICSS)) or with cannulae for microdialysis measures of nucleus accumbens dopamine (NAc DA). Changes in ICSS and NAc DA were examined after treatment with a visceral noxious stimulus (intraperitoneal injection of dilute lactic acid) or an exogenous κ-agonist (U69593). Additional studies examined the sensitivity of acid and U69593 effects to blockade by two analgesics (the nonsteroidal antiinflammatory drug ketoprofen and the μ-opioid agonist morphine) or by the κ-antagonist norbinaltorphimine (norBNI). The effects of acid were also examined on mRNA expression for prodynorphin (PDYN) and κ-opioid receptors (KORs) in mesocorticolimbic brain regions. Both acid and U69593 depressed ICSS and extracellular levels of NAc DA. Pain-related acid effects were blocked by ketoprofen and morphine but not by norBNI. The U69593 effects were blocked by norBNI but not by ketoprofen, and were only attenuated by morphine. Acid did not significantly alter PDYN or KOR in NAc, but it produced a delayed increase in PDYN in prefrontal cortex. These results support a key role for the mesolimbic DA system, but a more nuanced role for endogenous κ-opioid systems, in mediating acute pain-related behavioral depression in rats.

P56 – 1738 Anti-inflammatory treatment can reduce spontaneous recurrent seizure and depressive behavior in rats

P56 – 1738 Anti-inflammatory treatment can reduce spontaneous recurrent seizure and depressive behavior in rats