Dorsal hippocampal dopamine receptors are involved in mediating ethanol state-dependent memory

In the present study, the effects of bilateral injections of dopaminergic agents into the hippocampal CA1 regions (intra-CA1) on ethanol (EtOH) state-dependent memory were examined in mice. A single-trial step-down passive avoidance task was used for the assessment of memory retention in adult male NMRI mice. Pre-training intra-peritoneal (i.p.) administration of EtOH (0.25, 0.5 and 1 g/kg) dose dependently induced impairment of memory retention. Pre-test administration of EtOH (0.5 g/kg)-induced state-dependent retrieval of the memory acquired under pre-training EtOH (0.5 g/kg) influence. Intra-CA1 administration of the dopamine D1 receptor agonist, SKF 38393 (0.5, 1 and 2 g/mouse) or the dopamine D2 receptor agonist, quinpirole (0.25, 0.5 and 1 μg/mouse) alone cannot affect memory retention. While, pre-test intra-CA1 injection of SKF 38393 (2 μg/mouse, intra-CA1) or quinpirole (0.25, 0.5 and 1 μg/mouse, intra-CA1) improved pre-training EtOH (0.5 g/kg)-induced retrieval impairment. Moreover, pre-test administration of SKF 38393 (0.5, 1 and 2 μg/mouse, intra-CA1) or quinpirole (0.5 and 1 μg/mouse, intra-CA1) with an ineffective dose of EtOH (0.25 g/kg) significantly restored the retrieval and induced EtOH state-dependent memory. Furthermore, pre-training injection of the dopamine D1 receptor antagonist, SCH 23390 (4 μg/mouse), but not the dopamine D2 receptor antagonist, sulpiride, into the CA1 regions suppressed the learning of a single-trial passive avoidance task. Pre-test intra-CA1 injection of SCH 23390 (2 and 4 μg/mouse, intra-CA1) or sulpiride (2.5 and 5 μg/mouse, intra-CA1) 5 min before the administration of EtOH (0.5 g/kg, i.p.) dose dependently inhibited EtOH state-dependent memory. These findings implicate the involvement of a dorsal hippocampal dopaminergic mechanism in EtOH state-dependent memory and also it can be concluded that there may be a cross-state dependency between EtOH and dopamine. © 2006 Elsevier Inc. All rights reserved

Selective Cholinergic Depletion in Medial Septum Leads to Impaired Long Term Potentiation and Glutamatergic Synaptic Currents in the Hippocampus

Cholinergic depletion in the medial septum (MS) is associated with impaired hippocampal-dependent learning and memory. Here we investigated whether long term potentiation (LTP) and synaptic currents, mediated by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the CA1 hippocampal region, are affected following cholinergic lesions of the MS. Stereotaxic intra-medioseptal infusions of a selective immunotoxin, 192-saporin, against cholinergic neurons or sterile saline were made in adult rats. Four days after infusions, hippocampal slices were made and LTP, whole cell, and single channel (AMPA or NMDA receptor) currents were recorded. Results demonstrated impairment in the induction and expression of LTP in lesioned rats. Lesioned rats also showed decreases in synaptic currents from CA1 pyramidal cells and synaptosomal single channels of AMPA and NMDA receptors. Our results suggest that MS cholinergic afferents modulate LTP and glutamatergic currents in the CA1 region of the hippocampus, providing a potential synaptic mechanism for the learning and memory deficits observed in the rodent model of selective MS cholinergic lesioning

Involvement of central amygdala NMDA receptor mechanism in morphine state-dependent memory retrieval

In the current study, the effects of intra-central amygdala (CeA) administration of N-methyl-d-aspartate (NMDA) and its competitive antagonist, d-2-amino-5-phosphonopentanoic acid (D-AP5), on morphine state-dependent memory retrieval were investigated. Post-training subcutaneous (s.c.) administration of different doses of morphine (0.5, 2.5, 5 and 7.5. mg/kg) dose-dependently impaired memory. The response induced by post-training morphine (7.5. mg/kg) was reversed by pre-test administration of this drug (5 and 7.5. mg/kg), indicating morphine state-dependent memory retrieval. Pre-test intra-CeA administration of NMDA (0.01 and 0.05μg/rat) plus an ineffective dose of morphine (0.5. mg/kg, s.c.) restored memory impairment caused by post-training morphine (7.5. mg/kg). However, pre-test intra-CeA administration of NMDA (0.005-0.05μg/rat), alone, was ineffective on post-training morphine-induced amnesia. Furthermore, pre-test intra-CeA administration of the same doses of NMDA had no effect on memory retrieval. Pre-test intra-CeA administration of D-AP5 (0.1-1.0μg/rat) decreased morphine state-dependent memory retrieval. However, pre-test administration of D-AP5 (0.1-1μg/rat) alone decreased memory retrieval, but restored post-training morphine-induced amnesia. In conclusion, our results suggest which CeA may be potentially critical for morphine state-dependent memory retrieval and that CeA NMDA receptor mechanism(s) interact with the opiodergic system in the modulation of morphine state-dependent memory retrieval. © 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society

The time profile of morphine effect on different phases of inhibitory avoidance memory in rat

Backgrounds: The amnesic effect of morphine is well known in the laboratory animals. But, it is unclear that morphine at what times can exactly affect different phases of memory, including acquisition, consolidation, and retrieval. Therefore, we investigated the time profile of morphine's amnesic effect on passive (inhibitory) avoidance learning and memory in male Wistar rats. Methods: In order to evaluate the outcomes of pre- and post-training administrations of morphine, the animals were trained in a stepthrough type of passive avoidance task at various time points, and were tested 24 h after training to measure memory retrieval. Results: The results showed that acquisition of memory was impaired in the animals that received a dose of 7.5 mg/kg of morphine (Intraperitoneally) at 0, 30 min, and 1 h before training, as evidenced by a decrease in step-through latency on the test day. Post-training administrations of morphine at 30 min and 1h, 4h except for the time immediately after training, did not impair memory consolidation. The results also showed that pre-test administrations of morphine at 0 and 30 min before the test, impaired retrieval of inhibitory avoidance memory. Conclusion: Taken together, the results suggest that morphine, when injected at different time points before training, after training, or before testing affects different phases of inhibitory avoidance memory. With regard to the time of injections related to each phase, other experiments can be designed to investigate molecular mechanisms involved in the impairing effect of morphine in each phase

The Effects of Histaminergic Agents in the Nucleus ccumbens of Rats in the Elevated Plus-Maze Test of Anxiety

"n Objective: "n The nucleus accumbens (NAc) receive histaminergic neurons from tuberomammillary nuclei. There are reports indicating that central histamine systems are involved in many physiological behavioral processes, including anxiety. The aim of the present study was to assess whether the histaminergic system of the NAc is involved in anxiety-related behaviors. Methods: Rats were anesthetized with intra-peritoneal injection of ketamine hydrochloride, plus xylazine and then were placed in a stereotaxic apparatus. In addition, two stainless-steel cannuale were placed 2 mm above the nucleus accumbens shell. Seven days after recovery from surgery, the behavioral testing was started. As a model of anxiety, the elevated plus maze which is a useful test to investigate the effects of anxiogenic or anxiolytic drugs in rodents, was used in male Wistar rats.  "nResults: Intra-NAc administration of histamine (0.01, 0.1 and 1 µg/rat) increased the percentage of open arm time (%OAT) and open arm entries (%OAE) ,but not locomotor activity, indicating an anxiolytic response. Furthermore, bilateral  microinjections of different doses of the H1 receptor  antagonist pyrilamine (0.001, 0.01, 0.1 and 1 µg/rat) or the H2 receptor antagonist ranitidine (0.001, 0.01, 0.1 and 1 µg/rat) into the NAc increased %OAT and %OAE , but not locomotor activity. However, both histamine and histamine receptor antagonists showed an anxiolytic-like effect ; the antagonists (1 µg/rat) also decreased the histamine response. "n "n Conclusion: The results may indicate a modulatory effect for the H1 and H2 histamine receptors of nucleus accumbens in the anxiety behavior of rats

A move blocking based direct voltage model predictive control to enhance the dynamic performance of DC microgrids containing constant power loads

Abstract Here, a move blocking (MB) based direct voltage model predictive control (DVMPC) strategy is introduced to enhance the dynamic performance of a DC microgrid in presence of constant power loads (CPLs). For this aim, an automatic discrete dynamic model is first developed for a boost converter. Considering the CPL effects on the dynamic model of the boost converter, a model predictive control is then designed to directly regulate the output voltage of the converter. Move blocking strategy is finally integrated into DVMPC in order to extend the prediction horizon, and consequently, dealing with the non‐minimum phase characteristic of the boost converter. The dynamic performance of the boost converter with a CPL load in both continuous conduction mode (CCM) and discontinuous conduction mode (DCM) is evaluated using MB‐based DVMPC and traditional control strategies. The simulation results conducted using MATLAB/Simulink demonstrate that the proposed approach not only enhances the dynamic performance of the DC microgrid, but also reduces the computational burden on the processor. Moreover, experimental results have been performed to validate the proposed strategy. Finally, the stability analysis of the proposed direct voltage control is provided

Blockade of dorsal hippocampal dopamine receptors inhibits state-dependent learning induced by cannabinoid receptor agonist in mice

To clarify the interaction between cannabinnoid CB1 receptors and the dopaminergic system in memory processes, the effects of dopamine receptor agents on the state-dependent learning induced by the non-selective CB1/CB2 receptor agonist, WIN55,212-2 have been investigated in mice. Animals implanted with unilateral cannula at the CA1 region of the dorsal hippocampus and microinjected with WIN55,212-2 and/or dopaminergic agents, were tested using a single-trial step-down passive avoidance task. Intra-CA1 microinjections of WIN55,212-2 (0.1-1μg/mouse) immediately after training, decreased the step-down latency, indicating an amnesic effect of the drug. The amnesia was reversed by pre-test administration of the drug, suggesting state-dependent learning by the cannabinoid. Pre-test microinjection of apomorphine, a D1/D2 dopamine receptor agonist (0.1-0.3μg/mouse) into the CA1 region reversed the amnesia induced by post-training WIN55,212-2 (1μg/mouse). Moreover, pre-test co-administration of apomorphine with an ineffective dose of WIN55,212-2 (0.01μg/mouse), showed a reversion of the impairment on retention performance. Pre-test administration of the same doses of apomorphine did not show any response by itself. Pre-test intra-CA1 administration of a D1 dopamine receptor antagonist, SCH23390 (0.05-0.3μg/mouse) or D2 dopamine receptor antagonist, sulpiride (0.125-0.5μg/mouse) inhibited the expression of WIN55,212-2-induced state-dependent learning. Pre-test microinjection of the same doses of SCH23390 or sulpiride had no effect on WIN55,212-2-induced amnesia. Moreover, single injection of SCH23390 (0.2 and 0.3μg/mouse) or sulpiride (0.125μg/mouse) decreased memory retrieval. The results suggest that the dorsal hippocampal dopaminergic system participates in the modulation of WIN55,212-2-induced state-dependent learning. © 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society

Activation of dopamine D1 receptors in the medial septum improves scopolamine-induced amnesia in the dorsal hippocampus

In the present study, we investigated the influence of intra-medial septum (intra-MS) injections of dopamine D1 receptor agents on amnesia induced by intra-CA1 injections of a muscarinic acetylcholine receptor antagonist, scopolamine. This study used a step-through inhibitory (passive) avoidance task to assess memory in adult male Wistar rats. The results showed that in the animals that received post-training intra-MS injections of saline, intra-CA1 administrations of scopolamine (0.75, 1, and 2μg/rat) decreased inhibitory avoidance (IA) memory consolidation as evidenced by a decrease in step-through latency on the test day, which was suggestive of drug-induced amnesia. Post-training intra-MS injections of a dopamine D1 receptor agonist, SKF38393 at doses of 0.1, 0.15, and 0.3μg/rat had no effect, but at dose of 0.5μg/rat impaired IA memory consolidation. Interestingly, intra-MS injections of SKF38393 (0.15, 0.3 and 0.5μg/rat) significantly prevented amnesia induced by intra-CA1 injections of scopolamine (1μg/rat). Intra-MS injections of a dopamine D1 receptor antagonist, SCH23390 (0.5 and 0.75μg/rat) by itself impaired IA memory consolidation, and also at dose of 0.75μg/rat increased amnesia induced by intra-CA1 administrations of an ineffective dose of scopolamine (0.5μg/rat). Post-training intra-MS injections of ineffective doses of SCH23390 (0.1, 0.3 and 0.5μg/rat) prevented an effective dose of SKF38393 response to the impaired effect of scopolamine. These results suggest that dopamine D1 receptors in the MS via projection neurons to the hippocampus affect impairment of memory consolidation induced by intra-CA injections of scopolamine. © 2012 Elsevier B.V.