The purpose of the present study is to analyze the relationship between the telemetry electroencephalogram (EEG) changes of the prelimbic (PL) cortex and the drug-seeking behavior of morphine-induced conditioned place preference (CPP) rats by using the wavelet packet extraction and entropy measurement. The recording electrode was stereotactically implanted into the PL cortex of rats. The animals were then divided randomly into operation-only control and morphine-induced CPP groups, respectively. A CPP video system in combination with an EEG wireless telemetry device was used for recording EEG of PL cortex when the rats shuttled between black-white or white-black chambers. The telemetry recorded EEGs were analyzed by wavelet packet extraction, Welch power spectrum estimate, normalized amplitude and Shannon entropy algorithm. The results showed that, compared with operation-only control group, the left PL cortex's EEG of morphine-induced CPP group during black-white chamber shuttling exhibited the following changes: (1) the amplitude of average EEG for each frequency bands extracted by wavelet packet was reduced; (2) the Welch power intensity was increased significantly in 10-50 Hz EEG band (P < 0.01 or P < 0.05); (3) Shannon entropy was increased in β, γ₁, and γ₂waves of the EEG (P < 0.01 or P < 0.05); and (4) the average information entropy was reduced (P < 0.01). The results suggest that above mentioned EEG changes in morphine-induced CPP group rat may be related to animals' drug-seeking motivation and behavior launching.
Animals ; Conditioning (Psychology) ; Drug-Seeking Behavior ; Electroencephalography ; Entropy ; Morphine ; pharmacology ; Prefrontal Cortex ; drug effects ; Rats ; Telemetry ; Wavelet Analysis

The present study is aimed to investigated the firing activity of pyramidal neurons and interneurons in the medial prefrontal cortex (mPFC) in rats with bilateral intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) by using in vivo extracellular recording. The results showed that the injection of 5,7-DHT reduced the 5-hydroxytryptamine (5-HT) levels in the mPFC and dorsal raphe nucleus in the rats. The firing rate of mPFC pyramidal neurons in rats with 5,7-DHT injection was significantly higher than that of normal rats, and the firing pattern of these neurons also changed significantly towards a more burst-firing, while the injection decreased the firing rate of mPFC interneurons and changed the firing pattern of the interneurons towards a more irregular. These results indicate that the lesions of the serotonergic neurons lead to the changes in the firing activity of mPFC pyramidal neurons and interneurons, suggesting that serotonergic system plays an important role in the regulation of the neuronal activity in the mPFC.
5,7-Dihydroxytryptamine ; pharmacology ; Action Potentials ; Animals ; Dorsal Raphe Nucleus ; cytology ; Injections, Intraventricular ; Interneurons ; drug effects ; Prefrontal Cortex ; cytology ; Pyramidal Cells ; drug effects ; Rats ; Serotonin ; metabolism

OBJECTIVETo investigate the activity of pyramidal neurons in the medial prefrontal cortex (mPFC) of normal and 6-OHDA-lesioned rats and the responses of the neurons to 5-hydroxytryptamine-7 (5-HT(7)) receptor stimulation.

METHODSThe changes in spontaneous firing of the pyramidal neurons in the mPFC in response to 5-HT(7) receptor stimulation were observed by extracellular recording in normal and 6-OHDA-lesioned rats.

RESULTSBoth systemic and local administration of 5-HT(7) receptor agonist AS 19 resulted in 3 response patterns (excitation, inhibition and no change) of the pyramidal neurons in the mPFC of normal and 6-OHDA-lesioned rats. In normal rats, the predominant response of the pyramidal neurons to AS 19 stimulation was excitatory, and the inhibitory effect of systemically administered AS 19 was reversed by GABAA receptor antagonist picrotoxinin. In the lesioned rats, systemic administration of AS 19 also increased the mean firing rate of the pyramidal neurons, but the cumulative dose for producing excitation was higher than that in normal rats. Systemic administration of AS 19 produced an inhibitory effect in the lesioned rats, which was partially reversed by picrotoxinin. Local administration of AS 19 at the same dose did not change the ?ring rate of the neurons in the lesioned rats.

CONCLUSIONThe activity of mPFC pyramidal neurons is directly or indirectly regulated by 5-HT7 receptor, and degeneration of the nigrostriatal pathway leads to decreased response of these neurons to AS 19.

Action Potentials ; Animals ; Oxidopamine ; Parkinson Disease ; metabolism ; Prefrontal Cortex ; cytology ; Pyramidal Cells ; drug effects ; Rats ; Receptors, Serotonin ; metabolism ; Serotonin Receptor Agonists ; pharmacology

Alcoholism ; metabolism ; Animals ; Cyclin-Dependent Kinase 5 ; metabolism ; Glucosides ; pharmacology ; Male ; Prefrontal Cortex ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Stilbenes ; pharmacology

The deficiency of aquaporin-4 (AQP4) has been reported to alter release of neurotransmitters in the mouse brain. However, the functional relevance of AQP4 in mediating essential components of the general anaesthetic state is unknown. The aim of the present study was to investigate the role of AQP4 in general anaesthesia in mice lacking AQP4. The hypnotic effects of propofol, ketamine, and pentobarbital in AQP4 knockout (KO) and CD1 control mice were evaluated using the behavioural endpoint of loss of righting reflex (LORR). The effects of propofol on extracellular levels of amino acids in prefrontal cortex of freely moving mice were investigated using microdialysis coupled to high performance liquid chromatography with fluorescent detection. The result showed that, after receiving ketamine or pentobarbital, LORR occurred at earlier time in KO mice than that in control animals. Intraperitoneal injection of ketamine or pentobarbital increased the duration of LORR. After the administration of propofol, the duration of LORR was significantly reduced in KO mice compared with that in controls. Propofol increased the extracellular levels of aspartate, glutamate, and GABA, but not taurine, in prefrontal cortex. There were significant differences of increase patterns of the three kinds of neurotransmitters between KO and WT mice. Notably, the duration of GABA level increase correlated with the duration of LORR in two genotypes of mice. These results provide in vivo evidence of different responses in time-dependent release of excitatory and inhibitory neurotransmitters in prefrontal cortex of the two genotypes of mice. It is suggested that changes in anaesthetic reactions in mice with AQP4 loss may be related to neurotransmitter regulation, and that normal functioning of AQP4 plays an important role in the maintenance of anaesthetic hypnosis.
Anesthetics, Intravenous ; pharmacology ; Animals ; Aquaporin 4 ; deficiency ; genetics ; Hypnotics and Sedatives ; pharmacology ; Ketamine ; pharmacology ; Mice ; Mice, Knockout ; Neurotransmitter Agents ; metabolism ; Pentobarbital ; pharmacology ; Prefrontal Cortex ; drug effects ; metabolism ; Propofol ; pharmacology

OBJECTIVETo investigate the mechanisms of taurine (Tau) preventive effect on neurotoxicity induced by manganese (Mn) in rat's prefrontal cortex.

METHODSSD rats were divided into four groups after one week of observation: normal control:the group animals received daily intraperitoneal (ip.) injections of sterile saline for 3 months; Mn treated group (Mn): rats received ip. injection of MnCl(2).4H(2)O once a day for 3 months; Tau preventive group (Mn + Tau): The Mn level of this group were the same as Mn's, the Tau level 200 mg/kg, three times per week, for 3 months; Tau treated group (Mn-->Tau): After received the daily injection of Mn as Mn group for 3 months, the rats received Tau three times per week for 3 months. The dose of Mn and Tau were the same as above. The experiment lasted 6 months.

RESULTS(1) Mn induced apoptosis of neurons in rat's prefrontal cortex. The ratio of apoptosis of neurons in the Mn treated group [(20.0 +/- 4.3)%] was higher than that of the control group [(1.8 +/- 2.1)%] (P < 0.05) and the ratio of apoptosis in Tau preventive group (Mn + Tau) was lower than that of the Mn treated group (P < 0.05). (2) The production of MDA in Mn treated group was higher than the control group (P < 0.05) and the activity of SOD was lower than that in the control group. In Tau preventive group (Mn + Tau), Tau increased the activity of SOD and decreased the production of the MDA, with the significant difference level compared to the Mn treated group (P < 0.05).

CONCLUSIONMn induces apoptosis in rat's prefrontal cortex neurons. The main mechanisms of Tau preventing cytotoxicity against Mn is the reduction of the oxidative stress in prefrontal cortex neurons.

Animals ; Apoptosis ; drug effects ; Drug Antagonism ; Male ; Manganese ; toxicity ; Neurons ; drug effects ; metabolism ; pathology ; Neurotoxicity Syndromes ; etiology ; metabolism ; pathology ; prevention & control ; Prefrontal Cortex ; drug effects ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Taurine ; pharmacology

The aim of this study is to investigate the effect of fluoxetine (FLX) on the expressions of BDNF and Bcl-2 in the hippocampus, the amygdala and the prefrontal cortex of conditioned fear (CF) model mice. Forty eight mice were randomly divided into three groups, normal control group, CF stress group and FLX-pretreated CF group. The FLX-pretreated CF group was given FLX (10 mg x kg(-1) x d(-1)) for 7 days before CF stress. After CF stress model was established, all mice were given behavioral experiments to test whether FLX impaired or improved the auditory and contextual fear conditioning. Then mice were sacrificed. The expressions of BDNF and Bcl-2 were detected by Western blotting. The results showed that the freezing time of FLX-pretreated CF group was significantly lower than that of CF group; FLX pretreatment up-regulated the expression of Bcl-2 in the hippocampus at 1 d after CF stress (P < 0.001), but no significant differences was observed at 7 d; BDNF significantly increased in the hippocampus at 7 d (P < 0.001), but no differences at 1 d; the expressions of BDNF and Bcl-2 in the amygdala and the prefrontal cortex were of no obvious differences between CF group and FLX-pretreated CF group at 1 d or 7 d after CF stress. Parallel to these changes, pretreatment with FLX could affect histopathologic changes induced by CF stress. Furthermore, the results indicated that FLX pretreatment could protect against CF stress-induced neurological damage via the activation of BDNF and Bcl-2 in hippocampus.
Amygdala ; metabolism ; Animals ; Behavior, Animal ; Brain-Derived Neurotrophic Factor ; metabolism ; Fear ; drug effects ; Fluoxetine ; pharmacology ; Hippocampus ; metabolism ; Male ; Memory ; drug effects ; Mice ; Mice, Inbred ICR ; Prefrontal Cortex ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Random Allocation ; Stress, Psychological ; metabolism

OBJECTIVETo study the effects of Ginkgo biloba extract 50 (GBE50) on inflammatory cytokines and glia cell injury in the prefrontal cortex and hippocampus of aging rats and its probable mechanism. Methods Totally 45 male SD rats were randomly divided into 4 groups, i.e., the normal control group (n=12), the model group (n=11), the low dose GBE50 group (n=10), and the high dose GBE50 group (n=12). The aging rat model was intraperitoneally injected with D-galactose to establish the aging model for 42 days. Starting from the 22nd day of modeling, rats in the low dose GBE50 group and the high dose GBE50 group were administered by gastrogavage with 75 mg/kg and 150 mg/kg respectively. The protein contents and mRNA expressions of IL-1beta, IL-6, and TNF-a in the prefrontal cortex and hippocampus of rats were detected by radioimmunoassay and Real-time fluorescence quantitative PCR assay respectively. The ultrastructural changes of glia cells in the hippocampal CA1 region were observed by transmission electron microscope. Results The protein contents and mRNA expressions of IL-1beta and TNF-alpha in the prefrontal cortex and the hippocampus of aging rats obviously increased when compared with the normal control group (P < 0.05, P < 0.01). The content of IL-6 in the hippocampus of aging rats obviously decreased (P < 0.01). Compared with the model group, the protein content and mRNA expression of IL-1beta in the prefrontal cortex and the hippocampus were obviously downregulated in the low and high dose GBE50 groups. The content of TNF-alpha in the prefrontal cortex was obviously downregulated in the low and high dose GBE50 groups, the content of TNF-alpha in the hippocampus was obviously downregulated in the low dose GBE50 group (P < 0.05, P < 0.01). The content of IL-6 in the prefrontal cortex of the low dose GBE50 group was up-regulated. The content of IL-6 in the hippocampus of the high dose GBE50 group was also upregulated. The mRNA expression of IL-6 in the prefrontal cortex of the low and high dose GBE50 groups obviously increased (P < 0.05, P < 0.01). Low and high dose GBE50 showed obvious recovery on the ultrastructural damage of glia cells in the hippocampal CA1 region.

CONCLUSIONSGBE50 showed inhibitive effects on the inflammatory reaction of nerves of aging rats. Its mechanism might be possibly correlated with its regulatory effects on the cytokines in the prefrontal cortex and the hippocampus, as well as the ultrastructures of glia cells in the prefrontal cortex and hippocampus to some degree.

Aging ; Animals ; Cytokines ; metabolism ; Ginkgo biloba ; Hippocampus ; cytology ; drug effects ; Interleukin-1beta ; metabolism ; Interleukin-6 ; metabolism ; Male ; Neuroglia ; ultrastructure ; Plant Extracts ; pharmacology ; Prefrontal Cortex ; cytology ; drug effects ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo study the expression of phosphorylated-ERK1/2(p-ERK1/2)MAPK in the prefrontal lobe cortex (PFC), hippocampus (HP) and nucleus accumbens (Acb) in mice exposed to heroin in the uterus, and elucidate whether ERK MAPK signal transduction pathway participates in neurobehavioral teratogenicity induced by maternal heroin abuse.

METHODSAnimal model was established by subcutaneous administration of diacetylmorphine (10 mg/kg.d) to pregnant BALB/c mice on embryonic days 9-18, and their offspring were assigned to heroin and normal saline groups according to the maternal treatment. P-ERK1/2 expression in the PFC, HP and Acb were detected by RT-PCR and Western blot.

RESULTSThe heroin group had body weights similar to the normal saline group after birth. There were no significant differences in the p-ERK1/2 expression in the PFC, HP and Acb between the two groups.

CONCLUSIONSPrenatal exposure to 10 mg/kg heroin altered neither the body weight nor the general development in mice. The ERK1/2 MAPK signal pathway might not be involved in the neurobehavioral teratogenicity induced by prenatal heroin exposure.

Animals ; Body Weight ; drug effects ; Extracellular Signal-Regulated MAP Kinases ; genetics ; Female ; Fetus ; drug effects ; Heroin ; toxicity ; Hippocampus ; drug effects ; enzymology ; MAP Kinase Signaling System ; drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Nucleus Accumbens ; drug effects ; enzymology ; Prefrontal Cortex ; drug effects ; enzymology

OBJECTIVEThe effect of chronic morphine treatment on the I(A) (transient outward K+ current) of prefrontal cortical neurons of newborn rat. On this basis, we use AGS3 antibody to inhibit the function of AGS3, for observing the impact of AGS3 on the I(A), thus further explore the mechanism of AGS3 protein in morphine addiction.

METHODSBy using whole-cell patch-clamp technique, I(A) was recorded. In the whole-cell configuration, observed the impact of morphine on the current density-voltage curve (I-V) of I(A) and the effect of AGS3 antibody with three different concentrations on the I(A) of morphine treated rat prefrontal cortical neurons.

RESULTSMorphine increased the I(A). When the test potential was + 55 mV, different concentrations of AGS3, 10(-3) microg/L, 10(-2) micdrog/L and 10(-1) microg/L acted on morphine treated rat prefrontal cortical neurons, the enhanced IA by morphine was inhibited.

CONCLUSIONMorphine increases the I(A), AGS3 protein may participate in signal transduction pathway involved with I(A).

Animals ; Animals, Newborn ; Antibodies, Monoclonal ; pharmacology ; Carrier Proteins ; immunology ; metabolism ; Female ; Male ; Morphine ; adverse effects ; Neurons ; metabolism ; Patch-Clamp Techniques ; Potassium Channels ; drug effects ; Prefrontal Cortex ; metabolism ; Rats ; Rats, Sprague-Dawley ; Substance-Related Disorders ; metabolism ; physiopathology