Involvement of monoaminergic systems in the antidepressant-like effect of nobiletin

Nobiletin isolated from citrus peels up-regulates synaptic transmission and improves memory impairment in rodents. This study investigated the antidepressant-like effect of nobiletin in the forced swimming test (FST) and tail suspension test (TST) in mice. Additionally, the monoaminergic mechanisms involved in the antidepressant-like effect of nobiletin in mice were also assessed. Nobiletin (25, 50 and 100 mg/kg, p.o.) decreased the immobility time in both the FST and TST without locomotor alterations in the open-field test (OFT). The anti-immobility effect of nobiletin (50 mg/kg, p.o.) was completely prevented by the pretreatment of mice with WAY 100635 (0.1 mg/kg, s.c., a serotonin 5-HT_1A receptor antagonist), cyproheptadine (3 mg/kg, i.p., a serotonin 5-HT₂ receptor antagonist), prazosin (62.5 μg/kg, i.p., an α₁-adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., a dopamine D₁ receptor antagonist) or sulpiride (50 mg/kg, i.p., a dopamine D₂ receptor antagonist). On the other hand, the pretreatment of mice with yohimbine (1 mg/kg, i.p., an α₂-adrenoceptor antagonist) or propranolol (5 mg/kg, i.p., a β-adrenoceptor antagonist) did not block the antidepressant-like effect of nobiletin in the TST. Taken together, the data demonstrated that nobiletin produced an antidepressant-like effect that seems to be dependent on its interaction with the serotonergic, noradrenergic and dopaminergic systems. Thus, the present study suggests the therapeutic potential of this dietary flavonoid for the treatment of depression.     

Antidepressant-like effect of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol, a putative trace amine receptor ligand involves l-arginine-nitric oxide-cyclic guanosine monophosphate pathway

1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol is a novel putative trace amine receptor modulator hypothesized to be useful for treatment-resistant depression. In our previous study, we have demonstrated the antidepressant-like effect of this molecule in mouse forced swim and tail suspension tests and shown to act via modulating the levels of norepinephrine, serotonin and dopamine. The present study attempts to explore the involvement of l-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol in the mouse forced swim test. The antidepressant-like action of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol (8 mg/kg, i.p) was reversed by pretreatment with L-arginine (750 mg/kg, i.p.), a nitric oxide precursor. In contrast, pretreatment with methylene blue (a soluble guanlyate cyclase inhibitor and nitric oxide synthase (NOS) inhibitor) or 7-nitroindazole (a specific neuronal NOS inhibitor) potentiated the antidepressant-like effect of sub-effective dose of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol (2 mg/kg, i.p.) in this test model. Furthermore, the antidepressant-like effect of this molecule (8 mg/kg, i.p.) was reversed by sildenafil (5 mg/kg, i.p.), a phosphodiesterase inhibitor. In conclusion, the antidepressant-like action of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol involved L-arginine-nitric oxide-cyclic guanosine monophospate signaling pathway.     

Adenosine administration produces an antidepressant-like effect in mice: evidence for the involvement of A1 and A2A receptors

This study investigated the effect of adenosine in the forced swimming test (FST) and the tail suspension test (TST) in mice, and the contribution of adenosine A1 and A2A receptors to adenosine's antidepressant-like effect. The immobility time in the FST was reduced by adenosine given either by i.p. (5-10 mg/kg) or i.c.v. (0.01-10 microg/site) route. Adenosine (1-10 mg/kg, i.p.) also produced an antidepressant-like effect in the TST. No treatment affected locomotion in an open-field. The anti-immobility effect of adenosine (10 mg/kg, i.p.) in the FST was prevented by i.p. pretreatment of mice with caffeine (3 mg/kg), DPCPX (2 mg/kg) and ZM241385 (1 mg/kg). CHA (0.05 mg/kg, i.p.) and DPMA (1-5 mg/kg, i.p.) also produced an antidepressant-like effect in the FST. This is the first report of an antidepressant-like effect of adenosine in mice, apparently mediated through an interaction with A1 and A2A receptors.     

Role of 5-HT(1A) and 5-HT(1B) receptors in the antidepressant-like effect of piperine in the forced swim test

Our previous studies have showed that treating mice with piperine significantly decreased the immobility time of the animals in the forced swim test and tail suspension test, which was related to up-regulation of serotonin (5-HT) level in the brain. The purpose of this study is to explore the contribution of 5-HT receptors in the antidepressant-like effect of piperine. The results showed that pre-treating mice with methiothepin (a non-selective 5-HT receptor antagonist, 0.1 mg/kg, intraperitoneally), 4-(2′-methoxy-phenyl)-1-[2′-(n-2″-pyridinyl)-p-iodobenzamino-]ethyl-piperazine (a selective 5-HT_1A receptor antagonist, 1 mg/kg, subcutaneously) or 1-(2-(1-pyrrolyl)-phenoxy)-3-isopropylamino-2-propanol (a 5-HT_1B receptor antagonist, 2.5 mg/kg, intraperitoneally) was found to abolish the anti-immobility effect of piperine (10 mg/kg, intraperitoneally) in the forced swim test. On the other hand, a sub-effective dose of piperine (1 mg/kg, intraperitoneally) produced a synergistic antidepressant-like effect with (+)-8-hydroxy-2-(di-n-propylamino)tetralin (a 5-HT_1A receptor agonist, 1 mg/kg, intraperitoneally) or anpirtoline (a 5-HT_1B receptor agonist, 0.25 mg/kg, intraperitoneally). Taken together, these results suggest that the antidepressant-like effect of piperine in the mouse forced swim test may be mediated, at least in part, by the activation of 5-HT_1A and 5-HT_1B receptors.     

Evidence for the involvement of the opioid system in the agmatine antidepressant-like effect in the forced swimming test

This study investigated the involvement of the opioid system in the antidepressant-like effect of agmatine in the mouse forced swimming test (FST). The antidepressant-like effects of agmatine (10 mg/kg, i.p.), as well as those of fluoxetine (32 mg/kg, i.p, a selective serotonin reuptake inhibitor, SSRI) or morphine (5 mg/kg, s.c., a nonselective opioid receptor agonist) in the FST was completely blocked by pretreatment of mice with naloxone (1 mg/kg, i.p., a nonselective opioid receptor antagonist). Pretreatment of mice with naltrindole (3 mg/kg, i.p., a selective delta-opioid receptor antagonist), clocinnamox (1 mg/kg, i.p., an irreversible mu-opioid receptor antagonist), but not with 2-(3,4-dichlorophenyl)-N-methyl-N-[(1S)-1-(3-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl]acetamide (DIPPA; 1 mg/kg, i.p., a selective kappa-opioid receptor antagonist) completely blocked the anti-immobility effect of agmatine (10 mg/kg, i.p.) in the FST. These results firstly demonstrate that the antidepressant-like effects of agmatine in the FST seem to be mediated, at least in part, by an interaction with the opioid system, that involves an activation of delta- and mu-opioid receptors.     

A comparison between chronic exercise training and desipramine as treatments for the depression-like behavior of early-life maternal deprivation rats

We have established a depression-like behavioral animal model through maternal deprivation in rats during early life. By using this model, the curative effects of exercise training and desipramine, a tricyclic antidepressant, on the improvement of depression-like behavior in rats were compared. Four-week-old male maternal deprivation (MDP) or normal rats were divided into control and exercise groups. The exercise group animals were subjected to a protocol of running on a treadmill at a moderate intensity for 60 min/day, 5 days/week, for 5 weeks. Forced swimming and light/dark box tests were conducted here to identify the behavioral characters. In addition, the short treadmill test was also used to clarify their movement motivation. Our data showed that the immobility during the forced swimming test and retention time spent in the light box of MDP rats were significantly longer than those for the control group. However, there was no difference between MDP and normal rats in the short treadmill test. MDP rats subjected to the 3-week exercise training course could produce less immobility in the forced swimming test and less retention in the light box. However, with the long-term desipramine HCl treatment (21 days, 10 mg/kg, i.p.), MDP rats could express less immobility in the forced swimming test, but more immotility in the short treadmill test. These results suggested that exercise training and desipramine may mediate different mechanisms to ameliorate depression-like behavior in MDP rats.     

Orchiectomy modifies the antidepressant-like response of nicotine in the forced swimming test

Several studies have demonstrated that nicotine (NIC) exhibits antidepressant-like effects. In addition, it has been suggested that sexual hormones participate in the antidepressant actions of antidepressives. The present study was designed to analyze the effect of orchiectomy and the supplementation of testosterone propionate (TP) or 17β-estradiol (E₂) on the antidepressant properties of NIC using the forced swimming test (FST), as well as to determine possible changes in the FST during different time periods after orchiectomy. In order to evaluate the influences of orchiectomy on the effects of NIC, the study first evaluated the effects of different time periods on orchiectomized rats (15, 21, 30, 45 and 60 days) that were subjected to the FST. Then, different doses of NIC (0.2, 0.4, 0.8, 1.6 mg/kg, sc) were administered for 14 days to both intact and orchiectomized rats (after 21 day) which were then also subjected to the FST. Finally, the influence of the TP or E₂ supplementation on the antidepressant-like effect of NIC on orchiectomized rats (after 21 days) was also analyzed. Results reveal that orchiectomy significantly increased immobility behavior and decreased swimming and climbing up to 60 days after castration. In contrast, NIC decreased immobility behavior and increased swimming in intact rats; whereas orchiectomy suppressed this antidepressant effect of NIC. Only with E₂ supplementation was it possible to restore the sensitivity of the castrated rats to NIC. These results suggest that E₂ was able to facilitate the antidepressant response of NIC in orchiectomized rats.     

Fos-like immunoreactivity in rat dorsal raphe nuclei induced by alkaloid extract of Mitragyna speciosa

Mitragyna speciosa (MS) has been traditionally used for medicinal purposes especially in southern Thailand. Previously, an alkaloid extract of this plant was demonstrated to mediate antinociception, partly, through the descending serotonergic system. The present study investigated the stimulatory effect of the MS extract on the dorsal raphe nucleus and its antidepressant-like activity. The MS extract containing approximately 60% mitragynine as a major indole alkaloid was used to treat the animals. The stimulatory effect of the MS extract was determined by detecting the expression of the immediate early gene, cfos, in the dorsal raphe nucleus of male Wistar rats. The immunohistochemistry was used to detect Fos protein, the protein product of cfos gene. The present data show that a significant increase in Fos expression was observed following long-term administration of the MS extract (40 mg/kg) for 60 consecutive days. In addition, the antidepressant-like activity of the MS extract was determined by using the forced swimming test (FST) in male mice. The results show that a single injection (either 60 or 90 mg/kg doses) significantly decreased immobility time in the FST. These findings indicate that the MS extract has a stimulatory effect on the dorsal raphe nucleus and an antidepressant-like activity. Stimulation of this brain area has been known to cause antinociception. These findings suggest that the MS extract might produce antinociceptive and/or antidepressive actions partly through activation of the dorsal raphe nucleus. Moreover, the dorsal raphe nucleus may be one of site of MS action in the central nervous system.     

Antidepressant-like effect of diphenyl diselenide on rats exposed to malathion: Involvement of NaK ATPase activity

The antidepressant-like effect of repeated administration of diphenyl diselenide (PhSe)₂ in rats exposed to malathion is reported. The role of Na⁺K⁺ ATPase, acetylcholinesterase (AChE) and monoamine oxidase (MAO) activities and oxidative stress in antidepressant behavior were investigated in cerebral cortex of rats. Rats were exposed once a day for 3 consecutive days to malathion (50 mg/kg, intraperitoneal) and (PhSe)₂ (50 mg/kg, oral). To investigate the antidepressant-like behavior rats were submitted to the forced swimming test (FST) and open-field test (OFT). Thiobarbituric acid reactive species (TBARS) levels, enzymatic and non-enzymatic antioxidant defenses were carried out in cerebral cortex of rats. The results confirmed that malathion increased immobility time in the FST without altering the locomotor performance in the OFT. Treatment with (PhSe)₂ ameliorated performance in the FST without altering the crossing numbers in the OFT. The inhibition of Na⁺K⁺ ATPase activity caused by malathion was prevented by treatment with (PhSe)₂. Exposure to malathion did not alter parameters of oxidative stress as well as AChE and MAO activities in cerebral cortex of rats. In conclusion, (PhSe)₂ exerted antidepressant-like effect in rats exposed to malathion. Na⁺K⁺ ATPase activity is, at least in part, involved in (PhSe)₂ antidepressant-like behavior.     

Antidepressant-like action of nicotine in forced swimming test and brain serotonin in mice

An antidepressant-like action of nicotine has been suggested in the forced swimming test. The aim of the present study was to evaluate the relationship between the antidepressant-like action of nicotine and brain serotonin (5-HT) in mice. Nicotine at a dose of 0.2 mg/kg significantly (p < 0.05) decreased the duration of immobility time in forced swimming test. However, nicotine (0.01-1 mg/kg, s.c.) had no effect on locomotor activity in open-field test. Dopamine turnover in mouse whole brain was increased by nicotine (0.01-1 mg/kg, s.c.) in a dose-dependent manner, and nicotine at a dose of 0.05 mg/kg showed a significant increases in 5-HT turnover. Nicotine at a dose of 0.05 mg/kg markedly enhanced head twitch responses induced by (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a selective 5-HT2A/2C receptor agonist. These findings suggest that the involvement of nicotinic and serotonergic systems in the antidepressant-like effects of nicotine.     

Antidepressant-like effect of genipin in mice

The present study aimed to investigate the antidepressant potential of genipin and its possible mechanisms. Mouse models of depression including the forced swimming test (FST) and the tail suspension test (TST) were used to evaluate the effects of genipin. A possible mechanism was explored in the test of antagonism of reserpine-induced ptosis and hypothermia in mice. The contents of monoamine neurotransmitters and their metabolites including epinephrine (NE), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in mice hippocampi were determined by HPLC–ECD. The results showed that intra-gastric administration of genipin at 50, 100, 200 mg/kg or fluoxetine at 7.5 mg/kg for 7 days significantly reduced the duration of immobility in FST and TST, while it did not affect the locomotor activity in the open field test (OFT). However, the effect was not dose-dependent. When the mice were treated with genipin or fluoxetine for 7 days, both of them could antagonize reserpine-induced ptosis and hypothermia. The 5-HT and NE contents in mice hippocampi were decreased after the peritoneal injection of reserpine at 2.0 mg/kg. The pre-treatment with genipin at 50, 100, 200 mg/kg or fluoxetine at 7.5 mg/kg for 7 days could elevate the contents of NE and 5-HT in mice hippocampi significantly. The results suggest that compared with fluoxetine, genipin exerts antidepressant-like effects significantly. A possible mechanism, at least in part, is the regulation of the 5-HT and NE levels in the hippocampus.     

Involvement of PKA, MAPK/ERK and CaMKII, but not PKC in the acute antidepressant-like effect of memantine in mice

This study investigated the cellular signaling pathways involved in the acute antidepressant-like action of memantine in the forced swimming test (FST) in mice. The immobility time in the FST was reduced by memantine (3-10 mg/kg, i.p.). The anti-immobility effect of memantine (3 mg/kg, i.p.) was prevented by pretreatment with H-89 (1 microg/site, i.c.v., an inhibitor of PKA), PD098059 (5 microg/site, i.c.v., an inhibitor of MAPK/ERK), KN-62 (1 microg/site, i.c.v., an inhibitor of CaMKII), but not with chelerythrine (1 microg/site, i.c.v., an inhibitor of PKC). Taken together, these results firstly demonstrate that the acute antidepressant-like effect of memantine seems to be dependent on the cellular signaling modulated by PKA, CaMKII and MAPK/ERK, but not by PKC.     

An ERP study on the time course of facial trustworthiness appraisal

The neuropeptide galanin has been recognized as a possible neurotransmitter/neuromodulator, and in addition has been implicated in anxiety- and depression-related behaviors. The present study demonstrates increased locomotion and rearing after galanin (0.3 mg/kg) that was given intraperitoneally (i.p.) to intact Wistar rats which were tested 1 h later in the open field (OF). These effects, which suggest an anxiolytic-like action, were blocked by i.p. administered peptidic galanin antagonist M40. Further, the locomotion increase caused by galanin and the inhibitory effect of M40 persisted for 48 h without additional treatment. Rats exposed to restraint stress (lasting 60 min) for three consecutive days and tested 1 h after stress termination exhibited reduced locomotion and exploration in the OF. Galanin (0.3 and 1.0 mg/kg) given immediately after each stress exposure prevented the decrease of locomotion and exploration induced by stress in all trials. When the test was repeated 6 days later without stress and galanin treatment the reduction of locomotion produced by stress persisted; the anti-stress behavioral effects of both galanin doses were also present. Testing performed on the 12th day after the last stress and galanin treatment with 0.3 mg/kg revealed an increased locomotion compared with unstressed and stress-exposed rats. Our results demonstrate that behavioral effects of the peptide galanin are evident even after i.p. administration. These results also suggest that galanin elicits stress-modulatory action, and support the notion that the galaninergic system may serve as a drug target in stress-related conditions.     

Sub-chronic administration of rimonabant causes loss of antidepressive activity and decreases doublecortin immunoreactivity in the mouse hippocampus

Rimonabant is a cannabinoid receptor 1 antagonist, and is used to treat anorexia and obesity. However, it has been suggested that rimonabant may act as a depressant. In the present study, we investigated the depressive effects of rimonabant using behavioral and biochemical methods. A single treatment with rimonabant (10 mg/kg, p.o.) reduced immobility duration in the forced swimming test (FST) to a level similar to that observed for the tricyclic antidepressant, imipramine (15 mg/kg, i.p.). However, mice treated with rimonabant for 2 weeks did not show any significant reductions in immobility duration versus vehicle-treated controls. To investigate why the antidepressant effect of rimonabant disappeared after extended treatment, we carried out 5-bromo-2-deoxyuridine (BrdU) and doublecortin (DCX) immunohistochemistry assay. Numbers of BrdU-immunoreactive cells were not significantly changed after administering rimonabant (10 mg/kg, p.o.) for 2 weeks in the hippocampal dentate gyrus (DG), but interestingly, numbers of DCX-immunopositive cells in the DG were significantly reduced after 2 weeks of rimonabant treatment at doses of 1 or 10 mg/(kg day) compared with vehicle-treated controls (P < 0.05). These results suggest that sub-chronic treatments with rimonabant inhibit cell proliferation in DG, and that a lack of antidepressive activity may be related to a reduction in cell proliferation in this region.     

Electroacupuncture combined with clomipramine enhances antidepressant effect in rodents

The present study was designed to evaluate the antidepressant effect of electroacupuncture (EA) and the potential additive or synergistic effects of EA and clomipramine (CLO, a tricyclic antidepressant) in the mouse forced swimming test (FST) and chronic mild stress (CMS) induced depression-model rats. The FST is an antidepressant screening procedure performed initially to observe the immediate effects of EA and/or CLO on the immobility time. CLO (2.5, 5, 10, 20 and 60 mg/kg intraperitoneally) were administered at 23, 6 and 1h respectively prior to each test. EA was given at the ‘Bai-Hui’ (Du 20) and unilateral ‘An-Mian’ (EX 17) acupoints 1 h before each test. Immobility time was significantly reduced by EA and CLO at 2.5, 5, 10, 20 or 60 mg/kg, respectively. EA combined with 2.5 mg/kg CLO exhibited additive effects on the immobility time. In addition, rats were exposed chronically (1st–11th week) to a variety of mild unpredictable stressors. Depressed mood and anhedonia were recognized as a decrease in sucrose intake in the CMS rats. CLO at 2.5, 5 mg/kg and EA at the same acupoints and parameters were administrated on the CMS rats once every other day for 6 weeks (5th–11th week). The intake of 1% sucrose solution was reduced by CMS, which was restored to normal level after 6 weeks treatment with 5 mg/kg CLO or EA combined with 2.5 mg/kg CLO. However, neither the sucrose intake nor the sucrose preference in the depressive rats was significantly changed by the treatment with EA or 2.5 mg/kg CLO alone. These results demonstrated that EA combined with CLO at low doses has an additive or synergistic antidepressant action, and this combination may provide an effective strategy for depression management.     

Edaravone,a free radical scavenger,retards the development of amygdala kindling in rats

This study evaluated the antiepileptogenic effects of edaravone, a newly developed radical scavenger, on the amygdala kindling rats. The afterdischarge duration (ADD), AD threshold (ADT), and seizure severity in animals were measured to study the anticonvulsant effects of edaravone (2 mg/kg or 20 mg/kg i.p. for 7 days) on fully kindled seizures. Furthermore, for the study of antiepileptogenesis effects of the drug (2 mg/kg or 20 mg/kg i.p. for 7 days), not only ADD and seizure severity during kindling but also both the pre- and post-kindling ADT were measured. Edaravone neither induces nor inhibits fully kindled seizures regardless of the dose; however high-dose edaravone (20 mg/kg) retarded kindling development together with shortened ADD and elevated ADT. The present data suggest that high-dose edaravone has an antiepileptogenic drug effect for the prevention of epilepsy. However, other chronic models and clinical trials are needed to confirm the effects of edaravone on the prevention of human epilepsy.     

The stimulatory effects of caffeine with oseltamivir (Tamiflu) on light–dark behavior and open-field behavior in mice

Abnormal behaviors and death associated with the use of oseltamivir (Tamiflu^®) have emerged as a major issue in influenza patients taking the drug. Here, we investigated the mechanisms underlying the effects of oseltamivir on the behavior of mice using light–dark and open-field preference tests. Oseltamivir (75 and 150 mg/kg, intraperitoneally (i.p.)) alone affected neither time spent in the open area in the light–dark preference test nor ambulation in the open-field test at 2 h post-injection. However, a non-selective adenosine A₁/A₂ receptor antagonist, caffeine (10 mg/kg, i.p.) in combination with oseltamivir (150 mg/kg, i.p.) increased time spent in the open area in the light–dark preference test. This enhancement was not inhibited by a benzodiazepine receptor antagonist, flumazenil (10–20 mg/kg, subcutaneously (s.c.)). Enhancement of ambulation in the open-field test was also observed when caffeine (10 mg/kg, i.p.) was combined with oseltamivir (150 mg/kg, i.p.). This enhancement was inhibited by a dopamine D₂ receptor antagonist, haloperidol (0.1 mg/kg, s.c.). Furthermore, an adenosine A₂ receptor antagonist, SCH58261 (3 mg/kg, i.p.) in combination with oseltamivir (150 mg/kg, i.p.) increased ambulation in the open-field test, while an adenosine A₁ receptor antagonist, DPCPX (1–3 mg/kg, i.p.) did not. These findings suggest that the actions of oseltamivir may involve the dopamine and adenosine systems. Our findings suggest that due to the interaction between central blockade of adenosine A₂ receptors by caffeine, and oseltamivir-induced behavioral changes, patients being treated with oseltamivir should be closely monitored.     

Effects of acupuncture on chronic corticosterone-induced depression-like behavior and expression of neuropeptide Y in the rats

Repeated injection of corticosterone (CORT) induces dysregulation in the HPA axis, resulting in depression and anxiety. Many studies have shown that acupuncture, which is widely used for the treatment of stress and mental illness, in East Asian countries, is an effective therapeutic intervention for psychosomatic disorders. We investigated the influence of acupuncture therapy on chronic CORT-induced behavioral responses to the forced swimming test (FST) and elevated plus maze (EPM) and expression of neuropeptide Y (NPY) in the rat brain using immunohistochemistry. Male Sprague-Dawley rats were injected with CORT (40 mg/kg, i.p.) once daily for 19 consecutive days. The dysregulation of HPA axis by external injection of CORT was confirmed by measuring the CORT concentration in plasma and the expression level of CRF in hypothalamus. Acupuncture was performed at the PC6 acupoint for 5 min before CORT injection. Acupuncture significantly reduced depression- and anxiety-like behavior and increased NPY expression in the hypothalamus. These results demonstrated that stimulation of the PC6 acupoint suppresses the symptopathology of the hypoactivated HPA axis in chronic CORT-induced rat model of depression.     

Interaction between behavioral despair and addictive behaviors in rats

It has been suggested that depression can be either a cause or a consequence of drug abuse, providing a possible explanation for the fact that the prevalence of depression is almost 3-fold higher in drug abusers than in the general population. However, the interaction between depression and drug abuse has not been fully elucidated. To examine the interaction between behavioral despair and addictive behaviors, we used the Porsolt's forced swim test (FST) as a model of behavioral despair, and we used morphine conditioned place preference (CPP) and repeated morphine exposure as models of addictive behaviors. We found that rats exposed to a standard FST (15 min on day 0 training) rather than a weak FST (10 min on day 0 training) exhibited behavioral despair, which selectively potentiated morphine CPP (mCPP) but not food CPP (fCPP). The antidepressant imipramine (15 mg/kg, i.p.), which blocked the behavioral despair, prevented the standard FST potentiated morphine CPP. Conversely, repeated exposure to morphine (10 mg/kg, s.c.) for 6, 12 or 20 days decreased, had no effect on, or increased the immobility time, respectively, in the subsequent standard FST. Furthermore, repeated morphine exposure for 20 days exacerbated the pre-existing behavioral despair. Thus, our findings suggest that behavioral despair may increase the vulnerability of individuals to opiate abuse, which may in turn enhance behavioral despair.     

Isobolographic analysis of caramiphen and lidocaine on spinal anesthesia in rats

The aims of the study were to evaluate the spinal anesthetic effect of caramiphen and also assess spinal anesthetic interactions of caramiphen with lidocaine. Lidocaine, a common local anesthetic, was used as control. Dose-dependent responses of intrathecal caramiphen on spinal anesthesia were compared with lidocaine in rats. The interactions of caramiphen with lidocaine were evaluated via an isobolographic analysis. Caramiphen and lidocaine produced a dose-dependent local anesthetic effect as spinal anesthesia. On a 50% effective dose (ED₅₀) basis, the spinal anesthetic effect of caramiphen was more potent than lidocaine (P < 0.01 for each comparison). Co-administration of caramiphen with lidocaine produced an additive effect. Caramiphen and lidocaine are known to have local anesthetic effects as spinal anesthesia in rats. The spinal anesthetic effects of adding caramiphen to lidocaine are similar to the combinations of other anesthetics with lidocaine.