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Objective To investigate the effects of nicergoline on expressions of 5-hydroxytryptamine 1A receptor (5-HT1AR), D2 dopamine receptor (D2DR),α2A adrenaline receptor (α2AAR) in the hippocampal CA1 region and the serum level of apolipoprotein E4 (ApoE4) in a rat model of vascular depression (VD) . Methods Forty-eight male Sprague-Daw ley rats w ere randomly al ocated into a normal control group, a model group, fluoxetine group, a low-dose nicergoline group, a medium-dose nicergoline group, and a nicergoline high-dose group ( n=8 in each group). A rat model of VD w as induced by the ligation of bilateral common carotid arteries combined w ith chronic unpredictable mild stress (CUMS) plus single housing. The rats did not conduct CUMS or single housing in the normal control group, and the rats in the model group conducted CUMS and single housing. The rats in the fluoxetine group w ere given fluoxetine 1.3 mg/(kg· d) for gastric lavage for 3 w eeks at the beginning of CUMS and single housing. The rats in the low -, medium-and high-dose nicergoline groups w ere given nicergoline 0.9, 1.9 and 3.8 mg/(kg· d), respectively for gastric lavage for 3 w eeks at the beginning of CUMS and single housing. The normal control group and the model group w ere given equal volume of distil ed w ater for gastric lavage, once a day for 3 w eeks. Depression-like behavior w as evaluated using sucrose solution consumption and open-field test. Immunohistochemical staining and Western blot were used to detect the expressions of 5-HT1AR, D2DR, andα2AAR in the hippocampal CA1 region. Enzyme linked immunosorbent assay w as used to detect serum ApoE4 level. Results Before CUMS, the scores of horizontal and vertical movement and sucrose solution consumption in the model group, the fluoxetine group and each nicergoline group w ere decreased significantly compared w ith the normal control group (al P<0.01);w hile at 21 days after CUMS, those in the fluoxetine group and the nicergoline medium-and high-dose groups w ere significantly higher than those in the model group (al P<0.05). There w ere no significant differences betw een the fluoxetine group and each nicergoline group. The expression levels of 5-HT1A R, D2DR, α2A AR, and the serum ApoE4 in the model group, the fluoxetine group, and each nicergoline group w ere significantly higher than those in the normal control group. Those of the fluoxetine group and the nicergoline medium -and high-dose groups were significantly lower than the model group (al P<0.01), while there were no significant differences betw een the fluoxetine group and each nicergoline group. Conclusions Nicergoline can improve the depression-like behavior in VD rats. Its mechanism may be associated w ith the dow nregulation of 5-HT1AR, D2DR, α2AAR expressions and serum ApoE4 level.
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Objective To investigate the effect of 5-hydroxytryptamine 1A (5-HT1A) receptor agonists to improve micturition function in rats with diabetes mellitus (DM).Methods Fourteen female SD rats with the weight of 250 to 275 g were used.Seven rats were in the DM model group with intraperitoneal injection streptozotocin (STZ,65 mg/kg).Rats in the control group and DM group were anesthetized with urethane (1.3 g/kg) 8 weeks later.A polyethylene (PE)-50 catheter were placed in the left jugular vein for intravenous drug administration.A PE-90 catheter was inserted into the bladder,with the other end connected to a syringe pump for continuous infusion of saline and a pressure transducer for intravesical pressure monitor.Dose-response curves for 8-OH-DPAT were followed by WAY-100635 test.The capacity,residual volume,micturition volume,and EUS-EMG were measured.Results Compared to normal control,DM rats had a higher bladder capacity,residual volume,and a lower voiding efficiency.With increasing dose of 8-OH-DPAT (0.003-1.000 mg/kg,i.v.),the micturition volume increased from (2.15±0.49) ml to (2.85±0.21) ml,the residual volume decreased from (3.40±0.74)ml to (1.82±0.48) ml and voiding efficiency changed from (39.0±9.3)％ to (61.6±6.9)％.Control rats showed little change in cystometic variable.During the micturition,there was a dose-dependent increased phasic EUS activity correlated with the improved voiding efficiency.WAY-100635 (0.300 mg/kg,i.v.) reversed the 8-OH-DPAT-induced changes.Conclusions Both the bladder voiding efficiency and the periodic EUS activity decrease in DM rats.5-HT1A receptor agonist could promote periodic EUS activity and improve voiding efficiency.
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Objective To assess whether 5-HTR1A C( - 1019) G and GNβ3 C825T gene polymorphisms are associated with post-stroke depression (PSD) and explore the genetic mechanism of the pathogenesis of post-stroke depression. Methods All 159 patients with first stroke were divided into the PSD group and the control group according to HAMD scores. Their genotypes were determined with polymerase chain reaction and allele-specific restriction enzyme analysis. Results The frequency of 5-HTR1A (-1019) GG genotype(8/53,15. 1% ), G allele (44/106,41.5%)and GNβ3 825T allele(68/106,64. 2% ) were significantly higher in the post-stroke depression group than in the controls (5/106,4.7% ;35/212, 16. 5%; 113/212, 53.3%; ×2 = 23.204, 23. 655, 3. 392, all P ＜ 0. 05 ). Combined genotype analysis showed that individuals with both 5-HTR1A ( - 1019) G and GNβ3 825T allele ( OR =4. 980,95% CI 2. 429-10. 210,P =0. 000) had a higher risk than those with 5-HTR1 A (-1019) G allele ( OR = 3. 589,95% CI 2. 113-6. 096, P = 0. 000) or GNβ3 825T allele ( OR = 0. 638,95% CI 0.395-1. 031 ,P =0. 042) only for post-stroke depression. Conclusion The 5-HTR1A C( - 1019)G and GNβ3 C825T polymorphisms are predisposing genes of post-stroke depression. Our data also suggest a significant interaction between the 5-HTR1A ( - 1019)G allele and GNβ3 825T allele in post-stroke depression.
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Objective To investigate the change in expression of hippocampal neuronal 5-hyroxytryptamine1A(5-HT1A) receptor in a mouse model of chronic restraint stress.Methods Forty BALB/c male mice aged 6-9 months weighing 25-35 g were randomly divided into 2 groups ( n =20 each): normal control group (group C) and chronic restraint stress group( group S).In group S,the model of chronic restraint stress was established described by Wood et al.Tail suspension test,light-dark test and Morris water maze test were performed respectively at 1 d after successful establishment of the model.Immobility time,staying time in light compartment,and escape latency and frequency of crossing the original platform were recorded respectively in tail suspension test,light-dark test and Morris water maze test.Then the animals were sacrificed,hippocampi were removed for determination of the expression of 5-HT1A receptor in CA1 and CA3 regions of hippocampal neurons by immuno-histochemistry.ResultsCompared with group C,immobility time and escape latency were significantly prolonged,staying time in light compartment was shortened,frequency of crossing the original platform was decreased,and the expression of 5-HT1A receptor in hippocampal neurons was down-regulated in group S ( P ＜ 0.05 or 0.01 ).ConclusionChronic restraint stress can induce cognitive impairment in mice by down-regulating the expression of 5-HT1A receptor in hippocampal neurons.
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Objective To establish a cell line with overexpression of rat serotonin1A receptor (5-HT1AR).Methods Human neuroblastoma cells-SH-SY5Y were donated by cancer institute attached to the 4 th Affiliated Hospital, Hebei Medical University. Total RNA was extracted from brain tissues of male SD rats and rat 5-HT1A R was obtained by RT-PCR. Plasmid pc-DNA3. 1/hisC containing the rat 5-HT1AR (pc-DNA3.1/hisC-Rat-5-HT1AR)was constructed and transfected into SH-SY5Y cells. The transfected cells were isolated by G418 selection and SH-SY5Y-Rat-5-HT1A R cells were obtained. Expression of 5-HT1A R was detected by Western blot analysis. Cell viability was evaluated by MTT assay. SH-SY5Y-Rat-5-HT1AR cells were further observed for 5-HT1AR by immuno-fluorescence staining. Results Plasmid pc-DNA3. 1/hisC-Rat-5-HT1AR was successfully constructed by linking Rat-5-HT1A R with pc-DNA3.1/hisC and transfected into SH-SY5Y. The SH-SY5Y-Rat-5-HT1A R cells were more slender than SH-SY5Y cells with less and longer processes. MTT showed that the viability of SH-SY5Y-Rat-5-HT1A R cells was much lower than SH-SY5Y. Rat 5-HT1A R was expressed efficiently on the membrane of SH-SY5Y-Rat-5-HT1A R cells. Conclusion A cell line with overexpress of rat 5-HT1A R is successfully established.
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Objective To investigate the effect of tramadol on the expression of 5-HT1A receptor in the distal'cerebrospinal fluid contacting neurons (CSF-CNs) in mid-brain in a rat model of neuropathic pain. Methods Forty male SPF SD rats weighing 220-280 g were randomly divided into 5 groups (n = 8 each): group Ⅰ normal control (group C); group Ⅱ normal saline (group NS); group Ⅲ tramodol (group T); group Ⅳ neuropathic pain + normal saline (group NP+ NS) and group Ⅴ neuropathic pain + tramadol (group NP + T). Neuropathic pain was induced by chronic constrictive injury (CCI) in group Ⅳ and Ⅴ . Four silk ligatures were placed on the sciatic nerve at 1 mm intervals. In group Ⅱ (NS) and group Ⅲ (T) the sciatic nerve was exposed but not ligated and NS 2 ml/kg and tramadol 10 mg/kg were injected IP respectively, while in group Ⅳ and Ⅴ NS 2 ml/kg and tramadol 10 mg/kg were injected IP respectively on the 7th day after CCI. Paw withdrawal threshold (PWT) to von Frey filament stimulation and paw withdrawal latency (PWL) to noxious thermal stimuli were measured before (T1) and after IP NS or tramadol injection (T2) in group Ⅱ-Ⅴ. The distal CSF-CNs in the mid-brain was labelled with 30% cholera toxin subunit B and horseradish peroxidase compound (CB-HRP) 3 μl injected in left lateral cerebral ventricle. The expression of 5-HT1A receptors was measured by immuno-histochemistry. Results PWT and PWL were significantly decreased after CCI in group Ⅳ (NP + NS) and tramadol significantly inhibited the mechanical and thermal hyperalgesia in group Ⅴ (NP + T). There was no significant difference in the number of distal CSF-CNs among the 5 groups. CCI significantly down-regulated the expression of 5-HT1A in distal CSF-CNs in group Ⅳ(NP+ NS) as compared with group Ⅰ , Ⅱ and Ⅲ and tramadol significantly inhibited the CCI-induced downregulation of 5-HT1A receptor expression. Conclusion Tramadol can ease neuropathic pain by down-regulating the expression of 5-HT1A receptor in distal CSF-CNs in mid-brain.