Anxiety-like Behavior In Rats Research Articles

Tempol treatment reduces anxiety-like behaviors induced by multiple anxiogenic drugs in rats.

We have published that pharmacological induction of oxidative stress (OS) causes anxiety-like behavior in rats. Using animal models, we also have established that psychological stress induces OS and leads to anxiety-like behaviors. All evidence points towards the causal role of OS in anxiety-like behaviors. To fully ascertain the role of OS in anxiety-like behaviors, it is reasonable to test whether the pro-anxiety effects of anxiogenic drugs caffeine or N-methyl-beta-carboline-3-carboxamide (FG-7142) can be mitigated using agents that minimize OS. In this study, osmotic pumps were either filled with antioxidant tempol or saline. The pumps were attached to the catheter leading to the brain cannula and inserted into the subcutaneous pocket in the back pocket of the rat. Continuous i.c.v. infusion of saline or tempol in the lateral ventricle of the brain (4.3mmol/day) was maintained for 1 week. Rats were intraperitoneally injected either with saline or an anxiogenic drug one at a time. Two hours later all groups were subjected to behavioral assessments. Anxiety-like behavior tests (open-field, light-dark and elevated plus maze) suggested that tempol prevented anxiogenic drug-induced anxiety-like behavior in rats. Furthermore, anxiogenic drug-induced increase in stress examined via plasma corticosterone and increased oxidative stress levels assessed via plasma 8-isoprostane were prevented with tempol treatment. Protein carbonylation assay also suggested preventive effect of tempol in the prefrontal cortex brain region of rats. Antioxidant protein expression and pro-inflammatory cytokine levels indicate compromised antioxidant defense as well as an imbalance of inflammatory response.

Central administration of GPR55 receptor agonist and antagonist modulates anxiety‐related behaviors in rats

G-protein-coupled receptor 55 (GPR55) has been proposed as an atypical cannabinoid receptor, which is activated by lysophosphatidylinositols and some synthetic or endogenous cannabinoid molecules. The exact role of GPR55 receptors in the central nervous system especially in anxiety needs to be evaluated. In this study, the effects of intracerebroventricular (i.c.v.) administration of agonist and antagonist of GPR55 receptor on anxiety-related behaviors in rats were investigated. Here, O-1602 (GPR55 agonist) at the doses of 0.2, 1, and 5μg/rat increased %OAT and %OAE but not the locomotor activity, showing an anxiolytic response, whereas i.c.v. injection of ML193 (GPR55 antagonist) at the doses of 0.1 and 1μg/rat increased anxiety-like behaviors while causing locomotor impairment. The antagonistic effect of ML193 on the anxiolytic-like effect of O-1602 was also evaluated. The results showed that ML193 decreased the anxiolytic-like effect of O-1602. Based on these results, it may be concluded that central GPR55 may have a role in modulation of anxiety-like behaviors in rats. Further experiments are needed to elucidate the exact role of these receptors in anxiety.

Dopamine Receptor D2 and Associated microRNAs Are Involved in Stress Susceptibility and Resistance to Escitalopram Treatment.

Background:Early life stress has been demonstrated to increase the risk of developing depression in adulthood. However, the roles and associated molecular mechanisms of stresses in the onset and relapse of depression have yet to be fully elucidated.Methods:Depression-like behaviors were induced in rats by maternal deprivation and chronic unpredictable stress. Depression- and anxiety-like behaviors of rats, dopamine receptor D2 level, and microRNAs expression in rats’ brain tissues were measured.Results:Chronic unpredictable stress alone induced depression-like behaviors in rats, but maternal deprivation enhanced the effect of chronic unpredictable stress. Escitalopram significantly decreased depression-like behaviors in chronic unpredictable stress rats but was less effective in maternal deprivation with chronic unpredictable stress rats. Maternal deprivation increased dopamine receptor D2 messenger RNA expression and decreased microRNA-9 expression in the striatum. Chronic unpredictable stress increased dopamine receptor D2 mRNA and protein levels and decreased microRNA-9 expression in the nucleus accumbens. Furthermore, maternal deprivation enhanced the effect of chronic unpredictable stress on dopamine receptor D2 gene and microRNA-9 expression. Chronic unpredictable stress increased the expression of microRNA-326 in the nucleus accumbens but decreased it in the striatum, whereas maternal deprivation elevated microRNA-326 expression in the striatum. Escitalopram normalized microRNA-326 expression but had no effect on the expression of microRNA-9, dopamine receptor D2 mRNA, and dopamine receptor D2 protein in both the nucleus accumbens and striatum. The in vitro study showed that only microRNA-9 directly targeted the 3’ untranslated region of dopamine receptor D2 mRNA and inhibited dopamine receptor D2 protein expression.Conclusion:Early life stress enhanced the susceptibility to late life stress and resistance to escitalopram treatment through decreasing microRNA-9 expression and subsequently upregulating dopamine receptor D2 expression in the nucleus accumbens. microRNA-326 may be a novel target of escitalopram.

Acute isoproterenol induces anxiety-like behavior in rats and increases plasma content of extracellular vesicles

Several clinical observations have demonstrated a link between heart rate and anxiety or panic disorders. In these patients, β-adrenergic receptor function was altered. This prompted us to investigate whether the β-adrenergic receptor agonist isoproterenol, at a dose that stimulates peripheral β-adrenergic system but has no effects at the central nervous system, can induce anxiety-like behavior in rats. Moreover, some possible messengers involved in the peripheral to brain communication were investigated. Our results showed that isoproterenol (5mgkg−1 i.p.) increased heart rate, evoked anxiety-like behavior, did not result in motor impairments and increased extracellular vesicle content in the blood. Plasma corticosterone level was unmodified as well as vesicular Hsp70 content. Vesicular miR-208 was also unmodified indicating a source of increased extracellular vesicles different from cardiomyocytes. We can hypothesize that peripheral extracellular vesicles might contribute to the β-adrenergic receptor-evoked anxiety-like behavior, acting as peripheral signals in modulating the mental state.

Cannabinoid CB1 receptors in the dorsal hippocampus and prelimbic medial prefrontal cortex modulate anxiety-like behavior in rats: additional evidence.

Endocannabinoids (ECBs) such as anandamide (AEA) act by activating cannabinoid type 1 (CB1) or 2 (CB2) receptors. The anxiolytic effect of drugs that facilitate ECB effects is associated with increase in AEA levels in several encephalic areas, including the prefrontal cortex (PFC). Activation of CB1 receptors by CB1 agonists injected directly into these areas is usually anxiolytic. However, depending on the encephalic region being investigated and on the stressful experiences, opposite effects were observed, as reported in the ventral HIP. In addition, contradictory results have been reported after CB1 activation in the dorsal HIP (dHIP). Therefore, in the present paper we have attempted to verify if directly interfering with ECB metabolism/reuptake in the prelimbic (PL) portion of the medial PFC (MPFC) and dHIP would produce different effects in two conceptually distinct animal models: the elevated plus maze (EPM) and the Vogel conflict test (VCT). We observed that drugs which interfere with ECB reuptake/metabolism in both the PL and in the dentate gyrus of the dHIP induced anxiolytic-like effect, in both the EPM and in the VCT via CB1 receptors, suggesting that CB1 signaling in these brain regions modulates defensive responses to both innate and learned threatening stimuli. This data further strengthens previous results indicating modulation of hippocampal and MPFC activity via CB1 by ECBs, which could be therapeutically targeted to treat anxiety disorders.

Assessment of aqueous extract of Lemon verbena on anxiety-like behavior in rats

Aim: The purpose of the present study was to evaluate the anxiolytic effects of the aqueous extract of Lemon verbena on rats. Materials and Methods: In this study, aqueous extract of Lemon verbena leaves was prepared, and then male Wistar rats (200-230 g) were divided randomly into six experimental groups. Each group received a single intraperitoneal (IP) injection of saline, aqueous extract of Lemon verbena (10 mg/kg, 100 mg/kg, 500 mg/kg, 1,000 mg/kg)or diazepam, respectively. The level of anxiety was asserted by an elevated plus maze (EPM) 20 min after treatment. Statistical Analysis Used: Results were analyzed by one-way analysis of variance (ANOVA) and Tukey's post-hoc test. The results were expressed as mean ± standard error of mean (SEM). The differences were considered significant at P < 0.05. Results: The results of this study showed that there was a significant difference in the number of entrances into the open arms, spent time in the open arms and number of total entrances into the open and closed arms of the EPM between control, diazepam and extract-receiving groups (10 mg/kg, 100 mg/kg, 500 mg/kg, 1,000 mg/kg) and control. The numbers of entrances into the open arms, spent time in the open arms in extract receiving groups were significantly less than control group. Conclusion: These results indicated that acute administration of aqueous extract of Lemon verbena (≥10 mg/kg) increased anxiety-like behavior in rats in the EPM.

Effects of chronic sodium alendronate on depression and anxiety in a menopausal experimental model

ObjectiveDuring menopause, lower levels of estrogen may induce bone resorption as well as anxiety and depression. Bisphosphonates represent the first choice in the treatment of osteoporosis and no data are available concerning their effects on comorbid behavior alterations. Therefore, in this study, we evaluated the effects of chronic alendronate (1mg/kg/day) on depression and anxiety in an experimental animal model of menopause. MethodsFemale Wistar rats were ovariectomized or sham operated at 6–7 months of age. Two weeks after surgery, rats were randomized into four treatment (24 consecutive weeks) groups: (1) vehicle-treated SHAM group, (2) alendronate-treated SHAM group, (3) vehicle-treated ovariectomized group, and (4) alendronate-treated ovariectomized group. After treatment, we evaluated both depressive- and anxiety-like behavior through forced swimming test (FST) and open-field test (OF). Finally, the inverted screen test was used to assess the incapacitating effects of ovariectomy in rats. ResultsWe documented a significant and time-related increase in immobility times and in anxiety-like behavior in rats with ovariectomy in comparison to control sham group. Alendronate at 3months, but not at 6months, significantly decreased both immobility time and anxiety levels, but it significantly increased motor performance. Using the Pearson's test, we documented a significant correlation between behavior and motor performance. ConclusionDespite the apparent effects of alendronate on animal behavior, in our experiments, such effects seem to be mediated by an increase in motor performance.

Sensitization of neurons in the central nucleus of the amygdala via the decreased GABAergic inhibition contributes to the development of neuropathic pain-related anxiety-like behaviors in rats.

BackgroundDespite high prevalence of anxiety accompanying with chronic pain, the mechanisms underlying pain-related anxiety are largely unknown. With its well-documented role in pain and emotion processing, the amygdala may act as a key player in pathogenesis of neuropathic pain-related anxiety. Pain-related plasticity and sensitization of CeA (central nucleus of the amygdala) neurons have been shown in several models of chronic pain. In addition, firing pattern of neurons with spike output can powerfully affect functional output of the brain nucleus, and GABAergic neurons are crucial in the modulation of neuronal excitability. In this study, we first investigated whether pain-related plasticity (e.g. alteration of neuronal firing patterns) and sensitization of CeA neurons contribute to nerve injury-evoked anxiety in neuropathic rats. Furthermore, we explored whether GABAergic disinhibition is responsible for regulating firing patterns and intrinsic excitabilities of CeA neurons as well as for pain-related anxiety in neuropathic rats.ResultsWe discovered that spinal nerve ligation (SNL) produced neuropathic pain-related anxiety-like behaviors in rats, which could be specifically inhibited by intra-CeA administration of anti-anxiety drug diazepam. Moreover, we found potentiated plasticity and sensitization of CeA neurons in SNL-induced anxiety rats, of which including: 1) increased burst firing pattern and early-adapting firing pattern; 2) increased spike frequency and intrinsic excitability; 3) increased amplitude of both after-depolarized-potential (ADP) and sub-threshold membrane potential oscillation. In addition, we observed a remarkable reduction of GABAergic inhibition in CeA neurons in SNL-induced anxiety rats, which was proved to be important for altered firing patterns and hyperexcitability of CeA neurons, thereby greatly contributing to the development of neuropathic pain-related anxiety. Accordantly, activation of GABAergic inhibition by intra-CeA administration of muscimol, a selective GABAA receptors agonist, could inhibit SNL-induced anxiety-like behaviors in neuropathic rats. By contrast, suppression of GABAergic inhibition by intra-CeA administration of bicuculline, a selective GABAA receptors antagonist, produced anxiety-like behavior in normal rats.ConclusionsThis study suggests that reduction of GABAergic inhibition may be responsible for potentiated plasticity and sensitization of CeA neurons, which likely underlie the enhanced output of amygdala and neuropathic pain-related anxiety in SNL rats.Electronic supplementary materialThe online version of this article (doi:10.1186/s13041-014-0072-z) contains supplementary material, which is available to authorized users.

Central CRF2 receptor antagonism reduces anxiety states during amphetamine withdrawal

Increased depressive and anxiety-like behaviors are exhibited by rats and humans during withdrawal from psychostimulants. Anxiety-like behaviors observed during amphetamine withdrawal are mediated by increased expression and activity of corticotropin releasing factor type 2 (CRF2) receptors in the dorsal raphe nucleus (dRN). Anxiety-like behavior of rats during withdrawal can be reversed by CRF2 receptor antagonism in the dRN, but the efficacy of global central CRF2 receptor antagonism is unknown. Rats were treated with amphetamine (2.5mg/kg, ip.) or saline daily for 2 weeks, and were tested for anxiety-like behaviors during withdrawal. Rats undergoing withdrawal showed increased anxiety-like behavior, which was reduced by ventricular infusion of the CRF2 antagonist antisauvagine-30 (ASV 2μg/2μl). Surprisingly, ventricular ASV increased anxiety-like behavior in rats pre-treated with saline, but had an anxiolytic effect in un-treated rats. Western blots were performed to determine whether differences in CRF receptor densities could explain ASV-induced behavioral results. Saline pre-treated rats showed reduced CRF1 receptor expression in the lateral septum compared to amphetamine pre-treated and un-treated rats. Overall, these results suggest that central CRF2 antagonism reduces anxiety states during amphetamine withdrawal, and that behavioral effects may be dependent upon the balance of CRF1 and CRF2 receptor activity in anxiety-related regions.

Possible role of nitric oxide (NO) in the regulation of gender related differences in stress induced anxiogenesis in rats

Gender related differences in stress induced neurobehavioral disorders have been reported although the mechanisms involved are not yet clear. The present study investigated the role of nitric oxide, an important biomodulator in the sex related differences in stress induced anxiety like behavior in rats. Restraint stress (RS for 1 h) was used as the experimental stressor and the effects of NO modulators were assessed in the elevated plus maze (EPM) test in both male and female rats. No metabolites (NOx) and asymmetric dimethyl arginine (ADMA) were measured in brain homogenates of these rats for corroborative purposes. RS induced anxiogenesis in both male and female rats and such changes were greater in males as compared to females. The behavioral alterations were associated with enhanced levels of ADMA and reductions in levels of NOx in brain homogenates – the effects being greater in intensity in males as compared to females. Pretreatment with NO precursor L-arginine (500 mg/kg) reversed the RS induced behavioral and biochemical changes, while NO synthase inhibitor L-NAME (50 mg/kg) had opposite effects. Additionally, Formestane (50 mg/kg), an estrogen synthesis blocker, aggravated stress induced anxiogenesis with a corresponding increase in ADMA and decrease in NOx levels in the females. To our knowledge, this is the first report indicating the involvement of ADMA, an endogenous nitric oxide synthase inhibitor in stress induced neurobehavioral changes. Furthermore, it is also evident that nitric oxide and its interactions with estrogens play a crucial modulatory role in the differential anxiogenic response to stress among males and females.

Neuropeptide AF induces anxiety-like and antidepressant-like behavior in mice

Little is known about the action of neuropeptide AF (NPAF) on anxiety and depression. Only our previous study provides evidence that NPAF induces anxiety-like behavior in rats. Therefore, the aim of the present study was to investigate the action of NPAF on depression-like behavior and the underlying neurotransmissions in mice. In order to determine whether there are species differences between rats and mice, we have investigated the action of NPAF on anxiety-like behavior in mice as well. A modified forced swimming test (mFST) and an elevated plus maze test (EPMT) were used to investigate the depression and anxiety-related behaviors, respectively. Mice were treated with NPAF 30min prior to the tests. In the mFST, the animals were pretreated with a non-selective muscarinic acetylcholine receptor antagonist, atropine, a non-selective 5-HT2 serotonergic receptor antagonist, cyproheptadine, a mixed 5-HT1/5-HT2 serotonergic receptor antagonist, methysergide, a D2/D3/D4 dopamine receptor antagonist, haloperidol, a α1/α2β-adrenergic receptor antagonist, prazosin or a non-selective β-adrenergic receptor antagonist, propranolol 30min before the NPAF administration. In the mFST, NPAF decreased the immobility time and increased the climbing and swimming times. This action was reversed completely by methysergide and partially by atropine, whereas cyproheptadine, haloperidol, prazosin and propranolol were ineffective. In the EPMT, NPAF decreased the time spent in the arms (open/open+closed). Our results demonstrate that NPAF induces anti-depressant-like behavior in mice, which is mediated, at least in part, through 5HT2-serotonergic and muscarinic cholinergic neurotransmissions. In addition, the NPAF-induced anxiety is species-independent, since it develops also in mice.

Insular muscarinic signaling regulates anxiety-like behaviors in rats on the elevated plus-maze

Anxiety is one of the most prevalent neuropsychiatric disorders, and little is known about its pathogenesis. In order to investigate the neural mechanisms of this mental disorder, we used rat behavior in the elevated plus-maze as an animal model of anxiety and the insular cortex (insula) as a brain target. The microinjection of non-selective and selective M1 and M4 muscarinic acetylcholine receptor (mAChR) agonists or antagonists was used to explore whether the insular muscarinic receptor and its subtypes regulate levels of anxiety. The results showed that both non-selective and selective M1 and M4 mAChR agonists increased the time spent on exploring in the open arms, whereas antagonists decreased exploration. Our results indicate that activation of insular mAChRs could produce anxiolytic effects, whereas inhibition of insular mAChRs could increase anxiety. We concluded that the insular muscarinic system plays a role in the modulation of anxiety, and dysfunction of mAChR signaling may be involved in the mechanism of anxiogenesis.

Tu1793 Elevated Sympathetic Activity Induces Anxiety-Like Behavior in Rats Subjected to Neonatal Inflammation

G A A b st ra ct s neurons. In contrast to control rats, UK14304 decreased the amplitude of IPSC in 12 of 17 rats that underwent homotypic stress (2hrs restrain, 20min forced swim, 40min cold @4°C and 2hrs water avoidance) for 5 days in a concentration-dependent manner (91±1%, 78±1% and 53±9% of baseline amplitude in response to perfusion with 0.1, 1 and 3μM, respectively; P<0.05 vs control). Pretreatment with CRF had no additional inhibitory action on the UK14304-induced inhibition of GABAergic currents. Miniature strain gauges were applied to the anterior corpus of anaesthetized rats to record gastric motility. In control rats, DMV microinjections of the indirect sympathomimetic tyramine (4.5nmoles/60nl) reduced gastric motility to 50±10% of baseline (N=10); conversely, microinjections of tyramine in the brainstem of homotypic stress rats decreased gastric motility to 7±5% of baseline (N=2). These data suggest that homotypic stress induces an upregulation of catecholaminergic, including α2-mediated, responses in vagal neurocircuits resulting in an exaggerated vagallymediated gastroinhibition. Supported by DK55530 and DK78364

Effects of N-stearoylethanolamine on anxiety-like behavioral reactions of rats after chronic alcoholization

The effect of N-stearoylethanolamine (NSE) administration (isolated and combined with alcoholization) in the dose of 5 mg/kg on the behavior reactions of rats in the elevated plus maze was investigated. It was revealed that the isolated administration of NSE at the dose of 5 mg/kg rather reduced general locomotor activity of rats in elevated plus maze than increased their anxietylike behavior in these conditions. It was shown that chronic 30-day alcoholization increased anxiety-like behavior of rats in elevated plus maze but introduction of NSE on the background of alcohol eliminated changes of locomotor and emotional behavior of animals after alcoholization. The presence of significant changes in locomotor and emotional behavior of rats in elevated plus maze after administration of NSE at the dose of 5 mg/kg indicated a redundancy of such dose of the substance and therefore research of the influence on the behavior of smaller doses of NSE is very relevant.

Anxiety status affects nicotine‐ and baclofen‐induced locomotor activity, anxiety, and single‐trial conditioned place preference in male adolescent rats

Adolescents have an increased vulnerability to nicotine and anxiety may play a role in the development of nicotine abuse. One possible treatment for anxiety disorders and substance abuse is the GABAB agonist, baclofen. The aim of the present study was to determine the effect of anxiety-like behavior on single-trial nicotine conditioned place preference in adolescent rats, and to assess the action of baclofen. Baclofen was shown to have effects on locomotor and anxiety-like behavior in rats divided into high-anxiety and low-anxiety groups. Baclofen decreased locomotor behavior in high-anxiety rats. Baclofen alone failed to produce differences in anxiety-like behavior, but nicotine and baclofen + nicotine administration were anxiolytic. High- and low-anxiety groups also showed differences in single-trial nicotine-induced place preference. Only high-anxiety rats formed place preference to nicotine, while rats in the low-anxiety group formed no conditioned place preference. These results suggest that among adolescents, high-anxiety individuals are more likely to show preference for nicotine than low-anxiety individuals.

Effects of substance P and Sar-Met-SP, a NK1 agonist, in distinct amygdaloid nuclei on anxiety-like behavior in rats

The amygdala, together with the dorsal periaqueductal gray (dPAG), medial hypothalamus, and deep layers of the superior and inferior colliculi, constitutes the encephalic aversion system, which has been considered the main neural substrate for the organization of fear and anxiety. The basolateral nucleus of the amygdala (BLA) acts as a filter for aversive stimuli to higher structures while the central (CeA) and the medial (MeA) nuclei constitute the output for the autonomic and somatic components of the emotional reaction through major projections to the limbic and brainstem regions. Although some findings point to the distinct participation of the substance P (SP) and the NK1 receptors system in the different nuclei of the amygdala on the expression of emotional behaviors, it is not clear if this system modulates anxiety-like responses in the distinct nuclei of the amygdala as well as the dPAG. Thus, it was investigated if the injection of SP into the BLA, CeA, or MeA affects the expression of anxiety-like responses of rats submitted to the elevated plus-maze (EPM) test and, if the effects are mediated by NK1 receptors. The results showed that SP and Sar-Met-SP (NK1 receptor selective agonist) injected into the CeA and MeA, but not into the BLA, caused anxiogenic-like effects in the EPM. Altogether, the data indicates that the SP may mimic the effects of anxiogenic stimuli via NK1 receptor activation only in the CeA and MeA (amygdala's nuclei output) and may activate the neural mechanisms involved in the defensive reaction genesis. The SP/NK1 receptors system activation may be phasically involved in very specific aspects of anxiety behaviors.

Long-term effects of traumatic stress on subsequent contextual fear conditioning in rats

Exposure to stressful events affects subsequent sensitivity to fear. We investigated the long-term effects of a traumatic experience on subsequent contextual fear conditioning and anxiety-like behaviors in rats (Experiment 1). In addition, we tested whether the administration of the glucocorticoid synthesis inhibitor metyrapone (MET) attenuated the sensitization of fear induced by traumatic stress (Experiment 2). Male rats were subjected to a multiple stress (MS) session, which consisted of 4 foot shocks (1mA, 1s) and forced swimming for 20min, followed by exposure to a situational reminder 7days after the MS session. MET (25 or 100mg/kg, intraperitoneal) was administered 30min before MS. The contextual fear conditioning was performed 14days after MS. MS enhanced the conditioned fear response for at least 14days after the conditioning, and pretreatment with MET did not affect the enhancement of conditioned fear. These results suggest that glucocorticoid secretion triggered by MS is not involved in regulating the long-term stress-induced sensitization of fear.

Effects of Chronic Electroacupuncture on Depression‐ and Anxiety‐Like Behaviors in Rats with Chronic Neuropathic Pain

Growing evidence indicates that chronic neuropathic pain is frequently accompanied by an array of psychiatric diseases, such as depression and anxiety. Electroacupuncture (EA), as one therapy of traditional Chinese medicine, has displayed potent antidepressant-like effects in numerous clinical studies. The present study was designed to examine the possible effects of EA on the depressive and anxiety disorders induced by neuropathic pain. A classic rat model of neuropathic pain was produced by chronic constriction injury (CCI) of the sciatic nerve. EA was performed on acupoints “Bai-Hui” (GV20) and unilateral “Yang-Ling-Quan” (GB34). The antidepressive and anxiolytic effects of EA treatment were analyzed using the forced swimming test (FST) and the elevated plus maze (EPM) test, respectively. CCI resulted in remarkable depression- and anxiety-like behaviors, whereas the chronic EA treatment significantly improved the behavioral deficits of CCI rats. Moreover, the phosphorylation level of the NMDA receptor type 1 (NR1) subunit was decreased in the hippocampus of CCI rats. Intriguingly, continuous EA treatment effectively blocked this decrease in the levels of pNR1. These results suggested that EA has antidepressive and anxiolytic effects on rats with neuropathic pain and that this might be associated with restoring the phosphorylation of NR1 in the hippocampus.

Cannabinoid system of the lateral septum in the modulation of anxiety-like behaviors in rats.

A large body of evidence suggests that the cannabinoid CB1 receptor plays a key role in the regulation of emotional behaviors. The present study was designed to evaluate the effects of CB1 agonist and antagonist on anxiety-like behaviors in the lateral septum (LS) region of the rat brain using elevated plus maze test. Rats were anesthetized with ketamine and xylazine and special cannulas were inserted stereotaxically into the LS region. After 1 week of recovery, the effects of intra-LS administration of the CB1 receptor agonist, WIN 55,212-2 and CB1 receptor antagonist, AM251, on %OAT and %OAE were measured. Moreover, the effects of pretreatment with AM251 on the response induced by intra-LS administration of WIN 55,212-2 were also assessed. Intra-LS administration of WIN 55,212-2 (0.001, 0.005 and 0.5μg/rat) decreased the %OAT and %OAE but not locomotor activity, showing an anxiogenic-like response. Intra-LS injection of different doses of AM251 (0.001, 0.01 and 0.1 µg/rat) did not significantly alter the anxiety-like parameters on the plus-maze test. However, intra-LS injections of AM251 (0.01 µg/rat) significantly reversed WIN 55,212-2-induced anxiogenic-like effects. The results suggest that the cannabinoid system of the lateral septum modulates anxiety-like behavior through CB1 receptor.

Time-dependent analysis of nociception and anxiety-like behavior in rats submitted to persistent inflammation of the temporomandibular joint

Temporomandibular disorder (TMD) is prevalent in dental clinics and can involve problems with the masticatory muscles or the temporomandibular joints (TMJ). The pain of TMD is frequently associated with inflammation in the TMJs, but it's etiology is considered to be multifactorial and includes biologic, behavioral, environmental, social, emotional and cognitive factors. The purpose of this investigation was to evaluate the anxiety-like behavior in rats exposed to temporomandibular inflammation via injection of Freund's Adjuvant (CFA) with the elevated plus maze (EPM) and light/dark box (LDB) tests and to evaluate nociceptive behavior with the von Frey test at different periods. Moreover, this study measured TMJ inflammation using plasma extravasation (Evans blue test) and the intraarticular infiltration of polymorphonuclear neutrophils (myeloperoxidase quantification). The results showed that rats that were submitted to TMJ inflammation exhibited a decreased number of entries into the open arms of the EPM and a decrease in the time spent in the light compartment and in the number of transitions in the LDB. Additionally, the number of entries in closed arms in the EPM, used as indicator of locomotor activity, did not alter between treatments. Furthermore, increases in mechanical sensitivity and increases in plasma extravasation in the joint tissue occurred throughout the inflammation process, along with an increase in myeloperoxidase in the synovial fluid of TMJ. Our results suggest that the temporomandibular inflammation induced by CFA produced anxiety-like behaviors in rats and induced nociceptive behavior across different periods of inflammation.