Advances in study of structures and functions of conantokins / 浙江大学学报·医学版

Conantokin is a distinct family of conotoxin superfamily. Its members share considerable overall sequence homology. Their defining attributes include a high relative content of gamma-carboxyglutamic acid (Gla). They are generally devoid of disufide-loop contrasted with other conotoxins (except for conantokin-R). Upon binding to metal ions, the content of alpha-helix conformation increases in different degrees. They inhibit NMDA (N-methyl-D-aspartate) receptors; moreover, different conantokin species present different NMDA receptor subunit specificity. It can induce sleep-like symptoms in young mice when delivered intracranially. Analysis of sequences and structures indicates that the high conserved residues of these peptides are determinative in their structures and functions. In this article, the relationships of their structures and functions are reviewed in detail.

Chronic morphine drinking establishes morphine tolerance, but not addiction in Wistar rats / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

<p><b>OBJECTIVE</b>Some animal models apply morphine in the drinking water to generate addiction, but related reports are not free of conflicting results. Accordingly, this study aimed to figure out if chronic consumption of morphine in the drinking water can induce morphine addiction in Wistar rats.</p><p><b>METHODS</b>For 3 weeks, the animals received a daily morphine dose of 35 mg/kg by offering a calculated volume of sugar water (5% sucrose) with morphine (0.1 mg/ml) to each rat; animals receiving just sugar water served as controls. Immediately after the treatment phase, the tail immersion test was used to check for morphine tolerance, and all animals were then kept on tap water for one week (withdrawal phase). Afterwards, all rats were allowed to choose their drinking source by offering two bottles, containing sugar water without and with morphine, simultaneously for two days (preference phase).</p><p><b>RESULTS</b>While the chronic consumption of morphine led to a reduction in body weight and to morphine tolerance, the morphine-treated Wistar rats did not show any preference for the opiate-containing sugar water.</p><p><b>CONCLUSION</b>Body weight loss and tolerance do not reveal a condition of drug craving, and current animal models should be re-evaluated regarding their potential to establish morphine addicted animals.</p>

Effect of glycine site/NMDA receptor antagonist MRZ2/576 on the conditioned place preference and locomotor activity induced by morphine in mice / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

<p><b>OBJECTIVE</b>To study the effect of glycine site/NMDA (N-methyl-D-aspartate) receptor antagonist MRZ2/576 on the conditioned place preference (CPP) and locomotor activity induced by morphine in mice.</p><p><b>METHODS</b>Different doses (1.25, 2.5 and 5 mg/kg, i.p.) of MRZ2/576 were used to evaluate the effect of MRZ2/576 on the acquisition and expression of CPP induced by morphine (5 mg/kg) in mice. In addition, we examined the locomotor activity of mice in conditioning and testing phase of CPP paradigm.</p><p><b>RESULTS</b>MRZ2/576 alone could not establish place preference, but a 5 mg/kg dose of MRZ2/576 could block both acquisition and expression of morphine-induced CPP. In testing phase of CPP, there was no statistical difference for locomotor activity between the groups; injection of MRZ2/576 showed a dose-dependent decrease of locomotor activity on both control and morphine-treated mice, especially 5 mg/kg of MRZ2/576 significantly suppressed the locomotor activity of mice.</p><p><b>CONCLUSION</b>Based on the present results, we assume that MRZ2/576 can antagonize the rewarding effect of morphine, suggesting that this glycine site/NMDA receptor antagonist could be used to treat addictions due to its light side effect profile.</p>

Changes of CREB in rat hippocampus, prefrontal cortex and nucleus accumbens during three phases of morphine induced conditioned place preference in rats / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

<p><b>OBJECTIVE</b>To investigate the changes in CREB (cAMP response element binding protein) in hippocampus, PFC (prefrontal cortex) and NAc (nucleus accumbens) during three phases of morphine induced CPP (conditioned place preference) in rats, and to elucidate the role of CREB during the progress of conditioned place preference.</p><p><b>METHODS</b>Morphine induced CPP acquisition, extinction and drug primed reinstatement model was established, and CREB expression in each brain area was measured by Western Blot methods.</p><p><b>RESULTS</b>Eight alternating injections of morphine (10 mg/kg) induced CPP, and 8 d saline extinction training that extinguished CPP. CPP was reinstated following a priming injection of morphine (2.5 mg/kg). During the phases of CPP acquisition and reinstatement, the level of CREB expression was significantly changed in different brain areas.</p><p><b>CONCLUSION</b>It was proved that CPP model can be used as an effective tool to investigate the mechanisms underlying drug-induced reinstatement of drug seeking after extinction, and that morphine induced CPP and drug primed reinstatement may involve activation of the transcription factor CREB in several brain areas, suggesting that the CREB and its target gene regulation pathway may mediate the basic mechanism underlying opioid dependence and its drug seeking behavior.</p>

Establishment of computer-based video-tracking conditioned place preference experiment system in mice / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To establish the computer-based video-tracking conditioned place preference (CPP) system in mice.</p><p><b>METHODS</b>The CPP system was composed of computer, camera, soundproof box, shuttle box and analytical software. The results of morphine-induced conditioned place preference were used to evaluate the experiment system. And the effect of morphine-induced locomotor activity in drug-paired compartment was studied in mice.</p><p><b>RESULTS</b>Low (1 mg/kg, i.p.), moderate (3 mg/kg, 5 mg/kg, i.p.) and high (10 mg/kg, i.p.) dose of morphine significantly prolonged the time mice spent in drug-paired compartment compared with saline, but there was no dose-response relation. Moderate and high dose of morphine significantly enhanced locomotor activity, among which 5 mg/kg and 10 mg/kg morphine induced behavior sensitization in drug-paired compartment during the conditioning sessions.</p><p><b>CONCLUSION</b>The computer-based video-tracking conditioned place preference experiment system in mice established successfully is reliable and stable.</p>