By using intrathecal administration of antisense oligodeoxynucleotide (AS-ODN) against preprodynorphin mRNA in rats, we observed that this treatment could block both the formalin-induced behavioral nociceptive responses and the increased expression of dynorphin A (1-8) in the dorsal horn, with the increased expression of c-Fos protein being unchanged. For we have reported that intrathecal administration of AS-ODN against c-fos mRNA blocks the nociceptive responses and both the increased Fos protein and dynorphin A (1-8), the results of the present study suggest that: (1) Nociceptively induced spinal expression of dyorphin and Fos protein is involved in the transmission of nociceptive information at the spinal level and the expression of Fos protein is the up-stream event. (2) dynorphin may act as a pronociceptive, not an antinociceptive, factor in the modulation of the spinal hyperalgesic state.

Objective To investigate the exact protocol eliciting the hippocampal CA1 long-term depression (LTD) of rats in vivo and the effect of amyloid β-protein (Aβ) on the LTD.Method By applying test stimulation to Schaffer collateral in hippocampal CA1 region in rats,recorded the in vivo field excitatory postsynaptic potentials (fEPSPs) ;further,observed the induction of LTD with different low frequency stimulation (LFS) and investigated the effect of Aβ25-35 on the LTD.Results Prolonged LFS (1,5 and 10 Hz) but not paired-pulse stimulus (PPS) effectively elicited the LTD in the hippocampal CA1 region,with significantly decreased amplitude of fEPSPs after LFS ; 1 Hz 900 pulses group induced a stronger LTD,being (63.7 ± 3.8) ％ at 120 min post-LFS,lower (P ＜ 0.05) than (75.1 ± 3.2) ％ in 600 pulses group ; different frequencies (1,5 and 10 Hz) of LFS with same pulses induced similar degree of LTD,the amplitude of fEPSPs were (63.7 ± 3.8) ％,(61.2 ± 3.6) ％ and (59.8 ± 3.9) ％ respectively,without significant differences between any two groups (P ＞ 0.05) ; after applying 12.5 nmol and 25 nmol Aβ25-35,the amplitude of fEPSPs decreased to (63.2 ± 3.8) ％ and (46.8 ± 3.9) ％,respectively,and lower and than that in control ((73.9 ± 3.0) ％,P ＜ 0.05).Conclusion Prolonged LFS effectively induced in vivo hippocampal LTD of rats,which provides an important electrophysiological protocol for the study of synaptic plasticity; Aβ25-35 injection dont affect the baseline synaptic transmission,but dose-dependently enhance the in vivo hippocampal LTD of rats,indicating that Aβ-induced LTD facilitation may be involved the early impairment of learning and memory in Alzheimer's disease.

ObjectiveTo investigate the correlation of hippocampal synaptic plasticity with spatial learning and memory under normal and pathological condition,and provide experimental evidence for the coincidence of hippocampal late-phase long-term potentiation (L-LTP) and behavioral experiments.Methods 38 SD rats were randomly divided into two groups,control and AD model.First,Morris water maze was used to test the ability of spatial learning and memory of rats.The escape latencies for rats to search for an underwater platform in 5 days of navigation tests and the swimming time percentage in target qtuadrant on the 6th day after withdrawing the platform in probe trails were recorded.Then,in vivo hippocampus L-LTP of field excitatory postsynaptic potential (fEPSP)in CA1 region was recorded after delivering high frequency stimulation (HFS).ResultsBilateral intrahippocampal injection of 4 nmol amyloid β peptide ( Aβ 25-35 ) significantly impaired spatial learning and memory of rats in water maze tests,as well as in vivo hippocampal L-LTP.In control group,there was a significant negative correlation between the amplitude of fEPSP and the escape latency ( r =-0.8306,P ＜ 0.01 ) and a significant positive correlation between the amplitude of fEPSP and the swimming time percentage in target quadrant ( r=0.7709,P＜0.01 ).In AD model group,similar correlations were found,with a correlation coefficient of r =-0.7675 (P ＜0.01 ) and r =0.8049 (P ＜ 0.01 ),respectively.When putting all data from the two groups together,the hippocampal L-LTP was more correlated with escape latency ( r =-0.9124,P ＜ 0.01 ) and swimming time percentage ( r=0.9745,P＜0.01).ConclusionThere is very close correlation between the hippocampal L-LTP and the spatial learning and memory behavior in rats,suggesting that the hippocampal L-LTP may be involved in the electrophysiological mechanism of spatial learning and memory in rats,and the impairment of L-LTP could partly represent the deficits in cognitive function of animals.

Objective To observe the effect ofintraperitoneal injection of sodium benzoate on learning and memory abilities and morphology of hippocampal neurons in rats.Methods Thirty-six male SD rats were randomly divided into three groups:control group,sodium benzoate low-dose group and sodium benzoate high-dose group (n=12);intraperitoneal injection of 1 mL normal saline,60 mg/kg sodium benzoate or 120 mg/kg sodium benzoate was performed on the rats of three groups,respectively,for 20 d.Morris water maze test (place navigation,space exploration and visible platform searching) was used to assess the spatial learning and memory of rats,and HE staining was used to observe morphological changes in hippocampal neurons.Results The escape latency of rats in the sodium benzoate high-dose group was statistically significant in the navigation test as compared with that in the control group and the sodium benzoate low-dose group (P＜0.05);no significant difference was noted between sodium benzoate low-dose group and control group (P＞0.05).In probe test,no significant differences in the number crossing target quadrant were found after withdrawal of platform between groups (P＞0.05).HE staining showed that hippocampal CA1 neurons were sparse,showing a disordered arrangement in sodium benzoate low-dose group;the hippocampal neurons of CA1 region and fascia dentata region in sodium benzoate high dose group showed messed arrangement,nuclear pyknosis and cytoplasmic concentration as compared with that in the control group.Conclusion The high-dose sodium benzoate can decrease the learning ability of rats and impair hippocampal neurons.

Objective:To investigate possible neuromodulatory mechanisms involved in the involvement of parvalbu-min(PV)expression in the basal ganglia output nuclei,entopeduncular nucleus(EPN)and substantia nigra pars etic-ulata(SNr),in exercise-induced chronic fatigue impairs working memory capacity.Methods:Male SD rats were divid-ed into control group and Fatigue group by random number method,and a three-stage incremental load treadmill training program was selected to establish a chronic exhaustion exercise-induced fatigue rat model.The working memory ability of rats was assessed by the Y-maze autonomous alternation experiment.Immunohistochemical staining was used to ob-serve the expression of parvalbumin(PV)positive neurons and cysteine aspartate-specific protease-3(caspase-3)in EPN and SNr of rats.Results:The accuracy of voluntary alternation in the fatigue group was obviously lower than that in control group(P＜0.05).The results of immunohistochemical staining showed that the density of PV positive neu-rons and the degree of positive fiber staining in EPN and SNr in the fatigue group were obviously lower than those in the control group(P＜0.05,P＜0.01).The number of caspase-3 positive cells per unit area of EPN and SNr in the fa-tigue group was obviously higher than that in the control group(P＜0.05,P＜0.01).Conclusion:The mechanism of impairing working memory in rats caused by exercise-induced chronic fatigue may be related to the apoptosis of PV posi-tive neurons in EPN and SNr.