Biomedical subjects

Ji-Sheng Han

Publications and source records attributed to Ji-Sheng Han.

At least 19 recordsLinked to original sources

PubMed2006

The possible involvement of endogenous ligands for mu-, delta- and kappa-opioid receptors in modulating morphine-induced CPP expression in rats.

Previous studies suggested that electroacupuncture (EA) can suppress opioid dependence by the release of endogenous opioid peptides. To explore the site of action and the receptors involved, we tried to inject highly specific agonists for mu-, delta- and kappa-opioid receptors into the CNS to test whether it can suppress morphine-induced conditioned place preference (CPP) in the rat. Male Sprague-Dawley rats were trained with 4 mg/kg morphine, i.p. for 4 days to establish the CPP model. This CPP can be prevented by (a) i.p. injection of 3 mg/kg dose of morphine, (b) intracerebroventricular (i.c.v.) injection of micrograms doses of the selective mu-opioid receptor agonist DAMGO, delta-agonist DPDPE or kappa-agonist U-50,488H or (c) microinjection of DAMGO, DPDPE or U50488H into the shell of the nucleus accumbens (NAc). The results suggest that the release of endogenous mu-, delta- and kappa-opioid agonists in the NAc shell may play a role for EA suppression of opiate addiction.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed2006

NR2B-containing NMDA receptor is required for morphine-but not stress-induced reinstatement.

Glutamate receptors are known to be densely distributed in the forebrain rewarding circuits, and glutamatergic transmission is actively involved in the regulation of rewarding and reinstating effects of drugs of abuse. Here we investigated the possible involvement of the N-methyl-D-aspartate (NMDA) receptors in the reinstatement of extinguished morphine conditioned place preference (CPP) in rats. We found that previously extinguished morphine (3 mg/kg, i.p.) CPP was markedly reinstated by a priming injection of morphine (2 mg/kg, i.p.) or an acute environmental stressor (forced swim for 10 min), but not by the stress induced by a 24-h food deprivation. Parallel with this, protein levels of the NMDA receptor 2B subunit (NR2B) were elevated in the nucleus accumbens (NAc) and the hippocampus, but not the prefrontal cortex, of reinstated rats. Systemic administration of an NR2B selective antagonist ifenprodil (1, 3, 10 mg/kg, i.p.) attenuated the reinstatement induced by a priming morphine injection, although not by the forced swim. Ifenprodil (2.0 microg/rat) directly injected into the NAc shell or the CA1 region of the dorsal hippocampus produced a similar effect. These results indicate that the NR2B-containing NMDA receptors in the NAc and the dorsal hippocampus play a significant role in mediating the reinstatement of rewarding responses to morphine.

Amygdala↗

PubMed2006

Role of CDK5 in neuroprotection from serum deprivation by mu-opioid receptor agonist.

Cyclin-dependent kinase 5 (CDK5), a unique member of the CDK family of cyclin-dependent kinases, is predominantly expressed in postmitotic neurons with proposed roles in both cell survival and programmed cell death. To understand how CDK5 participates in such disparate cellular outcomes, we investigated whether activation of CDK5 could mediate neuroprotection from serum deprivation by mu-opioid receptor agonist in differentiated SH-SY5Y cells and primary hippocampal neurons. We found that CDK5 kinase activity decreased following serum deprivation in differentiated SH-SY5Y cells coincident with increased cell loss and activation of caspases cascade activation, which was reversed by opioid antagonist. Overexpression of CDK5 in serum-free medium reversed activation of caspase cascade and augmented DAMGO neuroprotection. Blocking CDK5 activity by pharmacologic inhibitor, roscovitine or overexpression of dominant negative CDK5 augmented activation of cell death markers and diminished mu-opioid receptor agonist protection. Reduction in CDK5 activity corresponded to reduction in protein levels of CDK5 activator p35 during serum deprivation which was also reversed by mu-opioid receptor agonist. Phosphorylation of STAT3 at Serine 727 by CDK5 decreased during serum deprivation, and partly recovered by mu-opioid agonist. PI3K signaling pathway was not required for CDK5-mediated mu-opioid neuroprotection against serum deprivation. These findings indicate that neuroprotection by mu-opioid receptor agonist against serum deprivation is mediated by activation of CDK5 through up-regulation of p35 and phosphorylation of STAT3 by CDK5 may contribute to the neuroprotection.

Animals↗

PubMed2006

Electroacupuncture suppresses expression of gastric ghrelin and hypothalamic NPY in chronic food restricted rats.

Electroacupuncture (EA) has been reported to reduce body weight in overweight subjects in clinical practice, as well as in rats and mice with diet-induced obesity. In the present study, this effect of EA was tested in lean rats subjected to long-term food restriction (FR, food was offered only 1 h/day). Two hertz EA administered once every other day produced a further reduction in body weight in FR rats. Exploration of the mechanism involved revealed significant downregulation of the orexigenic peptides: ghrelin in the stomach, and neuropeptide Y (NPY) but not Agouti-related peptide (AgRP) in the hypothalamus, which was in line with the reduction in food intake in rats receiving EA stimulation as compared with those receiving restraint only. Uncoupling protein 3 (UCP3), involved in accelerating energy expenditure, was not significantly altered. These results suggest that the EA-induced body weight reduction was due mainly to a decrease in food intake rather than an increase in energy expenditure. A reduction in the orexigenic peptides ghrelin and NPY may be involved in the underlying mechanism.

Agouti-Related Protein↗

PubMed2006

The role of NR2B containing NMDA receptor in place preference conditioned with morphine and natural reinforcers in rats.

It has been reported that N-methyl-D-aspartate (NMDA) receptor is implicated in drug addiction and antagonists of the NMDA receptor complex can inhibit the development and expression of conditioned place preference (CPP) induced by several addictive drugs, implying that this class of compounds might be considered as candidate for the treatment of substance abuse. To explore this possibility, it is important to evaluate whether the inhibitory effect of NMDA receptor antagonists would be confined to behaviors produced by drugs of abuse only, but not by natural reinforcers. According to the quantitative changes of NMDA receptor subunits, including NR1, NR2A, and NR2B, induced by diverse types of reinforcers, we chose NR2B subunit as the target of research. Experimental results showed that (1) an augmented expression of NR2B subunit was revealed by Western blotting in the nucleus accumbens (NAc) and the hippocampus in rats with CPP induced by morphine, but not by natural rewards such as food, novel environment and social interaction. (2) Ifenprodil, an antagonist highly selective for NR2B subunit of the NMDA receptor, produced a dose-dependent reduction in CPP induced by morphine and novel environment, but not that by food consumption and social interaction. Taking together, these findings suggested that NR2B containing NMDA receptor may be more involved with morphine reward rather than natural rewards, and that antagonism of NR2B may have a potential for the treatment of morphine abuse.

Analysis of Variance↗

PubMed2006

Dynamic neuronal responses in cortical and thalamic areas during different phases of formalin test in rats.

Although formalin-induced activity in primary afferent fibers and spinal dorsal horn is well described, the forebrain neural basis underlying each phase of behavior in formalin test has not yet been clarified. The present study was designed to investigate the cortical and thalamic neuronal responses and interactions among forebrain areas during different phases after subcutaneous injection of formalin. Formalin-induced neuronal activities were simultaneously recorded from primary somatosensory cortex (SI), anterior cingulate cortex (ACC) and medial dorsal (MD) and ventral posterior (VP) thalamus during different phases (i.e., first phase, interphase, second phase and third recovery phase starting from 70 min after injection) of formalin test, using a multi-channel, single-unit recording technique. Our results showed that, (i) unlike the responses in primary afferent fibers and spinal dorsal horn, many forebrain neurons displayed monophasic excitatory responses in the first hour after formalin injection, except a small portion of neurons which exhibited biphasic responses; (ii) the response patterns of many cortical and thalamic neurons changed from excitatory to inhibitory at the end of the second phase; (iii) the direction of information flow also changed dramatically, i.e., from cortex to thalamus and from the medial to the lateral pathway in the first hour, but reversed in phase 3. These results indicate that the changes of activity pattern in forebrain networks may underlie the emerging and subsiding of central sensitization-induced pain behavior in the second phase of formalin test.

Action Potentials↗

PubMed2006

Suppression of cue-induced heroin craving and cue-reactivity by single-trial transcutaneous electrical nerve stimulation at 2 Hz.

The purpose of the present study was to investigate the efficacy of 2 Hz transcutaneous electrical nerve stimulation (TENS) to reduce cue-induced heroin craving and the corresponding cardiovascular responses. Seventy heroin addicts with at least 1 month of abstinence were enrolled and randomly divided into two groups of 35, to receive single-trial 2 Hz TENS (TENS group) or mock TENS (mock group) during experimental procedure, respectively. They were required to express their degree of craving by visual analog scale before and after the presentation of a video-cue, and after TENS treatment, which lasted for 30 minutes. Heart rate and arterial blood pressure were simultaneously monitored in 56 cases, with 28 in each group. Results show that in mock group, video-cue induced a dramatic increase of craving score, which did not return to baseline in 150 minutes, whereas in the TENS group, 2 Hz TENS treatment produced a significant decrease of craving, reaching baseline in 90 minutes. Video-cue induced a significant increase of heart rate and systolic and diastolic blood pressure, which remained elevated for at least 60 minutes in the mock group; whereas in the TENS group, they returned to baseline immediately after the termination of TENS. These results indicate that the craving induced by a heroin-related cue can be immediately and significantly suppressed, and the cardiovascular activation totally abolished by a single-trial 2 Hz TENS for 30 minutes.

Adult↗

PubMed2005

Tramadol and dihydroetorphine produce synergistic analgesic effect and postpones acute opiate tolerance in rats.

The present study investigated whether a co-application of tramadol (TRA) and dihydroetorphine (DHE) would exert a synergy in analgesic effect and delay acute tolerance development. Intraperitoneal injection of TRA (in mg) and subcutaneous injection of DHE (in ng) were delivered in fixed proportions (1:6.25, 1:12.5, 1:25, 1:50, 1:100, and 1:200). The effect of analgesia was accessed by tail-flick test and analyzed with isobolographic analysis. For test of acute tolerance, six successive injections of either TRA (20 mg/kg) alone, DHE (1 000 ng/kg) alone, or a combination of TRA (20 mg/kg) and DHE (250 ng/kg) were administered. We found that (1) except for 1 mg : 6.25 ng and 1 mg : 50 ng, combinations, all the other ratios produced a significant synergy in their analgesic effect; (2) the effect of analgesia induced by repeated TRA plus DHE injections lasted significantly longer, indicating a slower onset of acute tolerance. These results indicate that TRA and DHE injections in certain dose ratios can induce synergistic analgesia, which is resistant against the development of acute tolerance.

Analgesics, Opioid↗

PubMed2005

Decreased dynorphin A (1-17) in the spinal cord of spastic rats after the compressive injury.

Spasticity in rat hindlimbs was induced by compressing cervical spinal cord with a wax ball. Ashworth score and H-reflex were measured 1 week after the surgery. The results showed that: (1) muscle spasm was detected in the hindlimbs a week after the operation and maintained at least 8 weeks, (2) in the spastic animals, dynorphin A (1-17)-ir decreased significantly in thoracic and lumbar segments of the spinal cord and (3) peripheral administration of kappa receptor agonist U50488H and electrical stimulation at 100 Hz effectively relieved the muscle spasm. Our data supported the note that the reduction of endogenous dynorphin A (1-17) might play an important role in the pathogenesis of spinally induced muscle spasticity and the replenishment of its shortage might relieve the spasticity.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed2005

Distribution of beacon immunoreactivity in the rat brain.

Beacon is a novel peptide isolated from the hypothalamus of Israeli sand rat. In the present study, we determined the distribution of beacon in the rat brain using immunohistochemical approach with a polyclonal antiserum directed against the synthetic C-terminal peptide fragment (47-73). The hypothalamus represented the major site of beacon-immunoreactive (IR) cell bodies that were concentrated in the paraventricular nucleus (PVN) and the supraoptic nucleus (SON). Additional immunostained cells were found in the septum, bed nucleus of the stria terminalis, subfornical organ and subcommissural organ. Beacon-IR fibers were seen with high density in the internal layer of the median eminence and low to moderate density in the external layer. Significant beacon-IR fibers were also seen in the nucleus of the solitary tract and lateral reticular formation. The beacon neurons found in the PVN were further characterized by double label immunohistochemistry. Several beacon-IR neurons that resided in the medial PVN were shown to coexpress corticotrophin-releasing hormone (CRH) and most labeled beacon fibers in the external layer of median eminence coexist with CRH. The topographical distribution of beacon-IR in the brain suggests multiple biological activities for beacon in addition to its proposed roles in modulating feeding behaviors and pituitary hormone release.

Animals↗

PubMed2005

Coding of peripheral electrical stimulation frequency in thalamocortical pathways.

Frequency information of the environment is an important feature for sensory perception. It has been demonstrated that cortical and thalamic neurons exhibited frequency-specific responses to peripheral stimulation. In the present study, we investigated the effects of 1-100 Hz peripheral electrical stimulations on various thalamic and cortical areas in awake rats. We used chronically implanted microelectrode arrays to record neural activities from the anterior cingulate cortex, primary somatosensory cortex, and medial dorsal and ventral posterior thalamus. The results revealed that cortical and thalamic neurons exhibited frequency-specific responses at both single-neuron and ensemble levels. Clusters of neurons responded to different frequency ranges with changes of both the peak firing rates and the phases of the peak responses in a stimulation cycle. Partial directed coherence analysis showed that information flowing between these recorded areas is also enhanced or inhibited in some frequency-specific pattern during stimulation. These evidences suggest that central nervous system may code environmental frequency information mainly with the activation of selected neural circuits according to their own intrinsic electrical properties. These properties, in turn, may facilitate or inhibit their responses when stimulation with specific frequency information arrives.

Animals↗

PubMed2005

Inhibition of hyperpolarization-activated current by ZD7288 suppresses ectopic discharges of injured dorsal root ganglion neurons in a rat model of neuropathic pain.

Peripheral nerve injury causes ectopic discharges of different firing patterns, which may play an important role in the development of neuropathic pain. The molecular mechanisms underlying the generation of ectopic discharges are still unclear. In the present study, by using in vivo teased fiber recording technique we examined the effect of ZD7288, a specific blocker of hyperpolarization-activated current (I(h)), on the ectopic discharges in the dorsal root ganglion (DRG) neurons injured by spinal nerve ligation. We found that ectopic discharges of all three firing patterns (tonic, bursting and irregular) were dose- and time-dependently inhibited by local application of ZD7288. Interestingly, the extent of suppression was negatively related to frequency of firing prior to application of ZD7288. We also observed that ZD7288 could alter the firing patterns of the ectopic discharges. At 100 microM, tonic firing pattern was gradually transformed into bursting type whereas at 1 mM, it could be transformed to integer multiples firing. These results indicate that I(h) might play a role in the generation of various forms of ectopic discharges in the injured DRG neurons and may thus be a possible target for neuropathic pain treatment.

Action Potentials↗

PubMed2005

Ectopic discharges from injured nerve fibers are highly correlated with tactile allodynia only in early, but not late, stage in rats with spinal nerve ligation.

It is widely accepted that ectopic discharges originated from injured sites and dorsal root ganglion (DRG) neurons after peripheral nerve injury contribute to neuropathic pain. However, it has been recently shown that ectopic discharges were not always necessary for neuropathic pain. In the present study, we aim to further examine the role of ectopic discharges in neuropathic pain in a spinal nerve ligation (SNL) model. With teased fiber recordings in vivo, the characteristics of ectopic discharges were observed over 14 days after SNL, and the correlation between ectopic discharges and tactile allodynia was analyzed. It was observed that ectopic discharges have three firing patterns (tonic, bursting, and irregular) after SNL, and proportions of these three patterns changed dynamically over time. The tonic and bursting types were dominant in the first 24 h following SNL, while the irregular type became the only pattern in the late stage (day 14). The average frequencies of ectopic discharges and the percentage of active filaments also changed over time, reaching the peak 24 h after SNL and then declined gradually. Ectopic discharges were highly correlated with tactile allodynia in the first 24 h following SNL, but surprisingly, not in the late stage of days 1 to 14. These findings suggest that ectopic discharges may be crucial in the triggering of neuropathic pain in the early stage, but their importance become more limited over time.

Action Potentials↗

PubMed2005

Effects of synchronous or asynchronous electroacupuncture stimulation with low versus high frequency on spinal opioid release and tail flick nociception.

Electroacupuncture stimulation (EAS) is known to change brain neurotransmitter release. In the present study, we investigated the effects of synchronous or asynchronous electroacupuncture stimulation with low versus high frequency on spinal opioid release and tail flick nociception. Rats were given "2/100 Hz" EAS, which stands for an asynchronous mode of stimulation, in which 2 Hz was alternated with 100 Hz, each lasting for 3 s, or "(2 + 100) Hz" EAS, a mode of stimulation in which 2 Hz stimulation was applied to the left hind leg simultaneously with 100 Hz stimulation on the right hind leg. The rats were subjected to the same total number of electrical stimulations in these two modes. Results were as follows: (1) 2/100 Hz EAS was 40% more potent than (2 + 100) Hz EAS (P < 0.01) in producing an anti-nociceptive effect. (2) Intrathecal (i.t.) injection of the mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr amide (CTOP) blocked in a dose-dependent manner the anti-nociceptive effect produced by 2/100 Hz EAS but not by (2 + 100) Hz EAS, whereas i.t. injection of the kappa-opioid receptor antagonist norbinaltorphimide (Nor-BNI) blocked the anti-nociceptive effect induced by both modes of EAS. (3) I.t. injection of endomorphin-2 antiserum blocked in a dose-dependent manner the anti-nociceptive effect of 2/100 Hz EAS but not that of (2 + 100) Hz EAS, whereas i.t. injection of dynorphin antiserum blocked the anti-nociceptive effect induced by both modes of stimulation. (4) 2/100 Hz EAS increased the release of both endomorphin-2 and dynorphin, whereas (2 + 100) Hz EAS increased the release of dynorphin but not of endmorphin-2. We conclude that the more potent anti-nociceptive effect induced by 2/100 Hz EAS, as compared with that of (2 + 100) Hz EAS, was due, at least partly, to the synergistic interaction of endomorphin-2 and dynorphin in rat spinal cord.

Afferent Pathways↗

PubMed2005

Repeated 2 Hz peripheral electrical stimulations suppress morphine-induced CPP and improve spatial memory ability in rats.

Our previous studies have shown that 2 Hz peripheral electrical stimulation (PES) can suppress morphine-induced conditioned place preference (CPP) in the rat, although the mechanisms remain unclear. Since CPP involves the mechanism of learning and memory, it is rational to ask whether the suppressive effect of repeated 2 Hz PES on morphine-induced CPP is due to an impairment of the function of spatial learning and memory. Rats were trained with 4 mg/kg morphine, i.p. for 4 days to establish the CPP. Twenty-four hours after the CPP testing, they were given PES at 2 Hz once a day for 1, 3 or 5 days, followed by another CPP testing. The results showed that (1) the morphine-induced CPP was significantly inhibited by 3 or 5 consecutive sessions, but not by single session of 2 Hz PES. (2) A test of spatial leaning and memory ability using the Morris water maze task revealed that 2 Hz PES per se exhibited a promoting, rather than a deteriorating effect on the ability of spatial memory. (3) 2 Hz PES by itself produced a moderate yet significant CPP. The results imply that (a) a low frequency PES can produce a rewarding effect as revealed by the CPP testing, which may account, at least in part, for its suppressive effect on morphine induced CPP, (b) the suppressive effect of PES on morphine induced CPP is not due to a deteriorating effect on the ability of spatial memory.

Animals↗

PubMed2005

[Natural rewarding and drug rewarding].

In the brain of animals and humans there is a rewarding mechanism to encourage the behavior that is beneficial for the living of the individual and for the prolongation of the generation. However, when this system is being abused by drugs of addiction, chronic adaptive changes may occur that would cause serious damage to the organism. The neural substrate of the rewarding system is mainly based on the dopaminergic pathway, starting from the ventral tegmental area of the midbrain and ended in the nucleus accumbens of the limbic brain. This pathway serves both natural rewarding such as food and sex as well as drug rewarding such as heroin and cocaine. This paper is aimed to discuss the similarities and differences between the natural and drug-induced rewarding in an attempt to block the latter without affecting the former.

Animals↗

PubMed2004

Involvement of ionotropic glutamate receptors in low frequency electroacupuncture analgesia in rats.

The present study was conducted to determine whether blockage of both N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid/kainate (AMPA/KA) receptors influences the induction of low frequency electroacupuncture (EA) analgesia. Although neither intrathecal injection of NMDA antagonist D-2-amino-5-phosphonopentanoic acid (D-AP-5) or AMPA/KA antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonami-de (NBQX) disodium alone had an effect on analgesia, spinal application of D-AP-5 and NBQX disodium significantly prevented analgesia induced by 2 Hz EA. The intrathecal injection of the excitatory amino acid NMDA produced analgesia for several minutes after intrathecal injection, as did EA stimulation. These results suggest that ionotropic glutamate receptors may be involved in the induction of 2 Hz EA analgesia.

Analgesia↗

PubMed2004

Ketamine enhances the efficacy to and delays the development of tolerance to electroacupuncture-induced antinociception in rats.

Our previous studies have shown that 100 Hz electroacupuncture (EA) produced antinociception through the release of endogenous opioids (mainly dynorphin) and the activated kappa-opioid receptors in normal rats. Acupuncture is an effective treatment in relieving pain, but it develops tolerance after repeated administration. It has been reported that N-methyl-D-aspartate (NMDA) receptor antagonists could increase the antinociceptive effects induced by morphine and delay the development of tolerance to morphine but nothing has yet been described to reduce EA tolerance. Here we test whether ketamine, a non-competitive NMDA receptor antagonist, would enhance 100 Hz EA antinociception as well as prevent or delay the development of chronic tolerance to 100 Hz EA in normal rats. The results are as follows: (1) ketamine injected intraperitoneally (i.p.) 15 min prior to EA enhanced the antinociceptive effects of 100 Hz EA at a dose of 5.0 mg/kg, but not 0.2 or 1.0 mg/kg. However, ketamine at either dose did not affect the basal nociceptive threshold (represented by tail-flick latency). (2) Ketamine at a dose of 5.0 mg/kg delayed the development of chronic tolerance to 100 Hz EA antinociception. We conclude that ketamine can enhance antinociception of 100 Hz EA and delay the tolerance to 100 Hz EA in rats. These results suggest that the development of 100 Hz EA tolerance to antinociception was mediated, at least in part, through peripheral NMDA receptors, which may be useful in improving the therapeutic effects of EA in the treatment of pain when EA tolerance occurs.

Adaptation, Physiological↗