The role of CA1 α-adrenoceptor on scopolamine induced memory impairment in male rats

Introduction: Similarities in the memory impairment between Alzheimer patients and scopolamine treated animals have been reported. In the present study, the possible role of α-adrenergic receptors of the dorsal hippocampus on scopolamine state-dependent memory in adult male Wistar rats was evaluated. Methods: The animals were bilaterally implanted with chronic cannulae in the CA1 regions of the dorsal hippocampus, trained in a step-through type inhibitory avoidance task, and tested 24 h after training to measure step-through latency. Results: Post-training intra-CA1 administration of scopolamine (0.5 and 2μg/rat) dose-dependently reduced the step-through latency, showing an amnestic response. Amnesia produced by post-training scopolamine (2 μg/rat) was reversed by pre-test administration of the scopolamine (0.5 and 2 μg/rat) that is due to a state-dependent effect. Pre-test intra-CA1 injection of α1-adrenoceptor agonist, phenylephrine (0.25, 0.5 μg/rat) in the dose range that we used, could not affect memory impairment induced by post-training injection of scopolamine (2 μg/rat). However intra-CA1 pretest injection of α2-adrenoceptor agonist, clonidine (0.5 μg/rat) improved post-training scopolamine (2 μg/rat) intra-CA1 injection induced retrieval impairment. Furthermore, pre-test intra-CA1 microinjection of phenylephrine (0.25 and 0.5 μg/rat) or clonidine (0.25 and 0.5 μg/rat) with an ineffective dose of scopolamine (0.25 μg/rat), synergistically improved memory performance impaired by post-training scopolamine (2 μg/rat). Our results also showed that, pre-test injection of α1-receptor antagonist prazosin (1, 2 μg/rat) or α2-receptors antagonist yohimbine (1, 2 μg/rat) before effective dose of scopolamine (2 μg/rat) prevented the improvement of memory by pre-test scopolamine. Conclusion: These results suggest that α1- and α2-adrenergic receptors of the dorsal hippocampal CA1 region may play an important role in scopolamine-induced amnesia and scopolamine state-dependent memory

Involvement of dorsal hippocampal α-adrenergic receptors in the effect of scopolamine on memory retrieval in inhibitory avoidance task

The present study evaluated the possible role of α-adrenergic receptors of the dorsal hippocampus on scopolamine-induced amnesia and scopolamine state-dependent memory in adult male Wistar rats. The animals were bilaterally implanted with chronic cannulae in the CA1 regions of the dorsal hippocampus, trained in a step-through type inhibitory avoidance task, and tested 24. h after training to measure step-through latency. Results indicate that post-training or pre-test intra-CA1 administration of scopolamine (1 and 2μg/rat) dose-dependently reduced the step-through latency, showing an amnestic response. Amnesia produced by post-training scopolamine (2μg/rat) was reversed by pre-test administration of the scopolamine that is due to a state-dependent effect. Interestingly, pre-test intra-CA1 microinjection of α1-adrenergic agonist, phenylephrine (1 and 2μg/rat) or α2-adrenergic agonist, clonidine improved post-training scopolamine (2μg/rat)-induced retrieval impairment. Furthermore, pre-test intra-CA1 microinjection of phenylephrine (0.25, 0.5 and 1 μg/rat) or clonidine (0.25, 0.5 and 1 μg/rat) with an ineffective dose of scopolamine (0.25 μg/rat), synergistically improved memory performance impaired by post-training scopolamine. On the other hand, pre-test injection of α1-receptors antagonist prazosin (1 and 2 μg/rat) or α2-receptors antagonist yohimbine (1 and 2 μg/rat) prevented the restoration of memory by pre-test scopolamine. It is important to note that pre-test intra-CA1 administration of the same doses of prazosin or yohimbine, alone did not affect memory retrieval. These results suggest that α1- and α2-adrenergic receptors of the dorsal hippocampal CA1 regions may play an important role in scopolamine-induced amnesia and scopolamine state-dependent memory. © 2010 Elsevier Inc

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

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.

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

Interaction between Cannabinoidergic System and H2 Receptors in CA1 Region upon Anxiety-like Behaviors in Hole-Board Test

Background and Objectives: Cannabinoids produce a wide array of effects on different species and interact with different neurotransmitter systems in the brain. In the present study, the effects of histaminergic and cannabinoidregic systems as well as their interactions on anxiety-related behaviors were examined on mice.Methods: In this study, at first mice were anesthetized with intra-peritoneal injection of ketamine hydrochloride and xylazine. They were then placed in a stereotaxic apparatus. Two stainless-steel cannuale were placed one mm above CA1 regions of the dorsal hippocampus. After that, seventeen groups of animals were tested with hole board apparatus for measuring anxiety behavior. For the statistical analysis, One-way analysis of variance (ANOVA) and Dunnett's test were used.Results: Intra-CA1 injection of WIN55,212-2 (0.1, 0.5µg/mice) did not modify anxiety-related behaviors in mice. But administration of AM251 (25 and 50ng/mice), histamine or ranitidine (5µg/mice) induced anxiogenic-like response. Also, co-administration of WIN55, 212-2 with histaminergic agents, decreased the anxiogenic-like response of histamine, but not that of ranitidine. Co-administration of an ineffective dose of AM251 with histaminergic drugs did not alter the response induced by these drugs. In all the experiments, locomotor activity was not significantly changed. Conclusion: These results showed that there may be a partial interaction between the cannabinoidergic and the histaminergic systems of the dorsal hippocampus on anxiety-like behaviors

Mechanism of the Interaction of Cannabinoid System in Central Amygdale with Opioid System

Background and objectivesCannabinoids which are active compounds of marijuana show some pharmacological effects similar to the opioids. There are also functional interactions between both cannabinoid and opioid systems. In this study we investigated the role of cannabinoid receptors in central amygdala and its interaction with opioid system.MethodsIn the present study, we investigated the effects of intraperitoneal injection of opioid drugs on response-induced by intra-amygdala (intra-Amyg) microinjection of cannabinoid agents in rats, using elevated plus-maze test of anxiety. ResultsIntraperitoneal injection of morphine (3, 6 and 9 mg/kg) increased %OAT and %OAE, but not locomotor activity, showing an anxiolytic response. However, some doses of the opioid receptor antagonist, naloxone reduced %OAT and locomotor activity as well. Intra-Amyg administration of CB1 cannabinoid receptor agonist, ACPA (at the dose of 1.25 and 5 ng/rat) increased %OAT and %OAE but not locomotor activity, thus showing an anxiolytic response, which was increased by morphine (6 mg/kg, i.p.) without any interaction. Naloxone also reduced ACPA effects. Intra-Amyg administration of CB1 cannabinoid receptor antagonist, AM251 (2.5, 25 and 100 ng/rat) did not alter %OAT and %OAE but higher doses of drug (25 and 100 ng/rat) reduced locomotor activity. However, the drug in combination of morphine anxiolytic response and with naloxone decreased anxiety.ConclusionThe results may indicate an anxiolytic for CB1 cannabinoid. Our results also showed that opioid system may have interaction with cannabinoid receptor in the amygdale. Keywords: Cannabinoids, Morphine; Naloxone, Anxiety, Elevated Plus-Maz

The interaction between harmane and nicotinic receptors of dorsal hippocampus in a hole-board test of anxiety in mice

Background: β-carboline alkaloids, such as harmane, are found in common plant-derived foodstuffs and plant-derived inhalation components of tobacco. In the present study, the involvement of dorsal hippocampus nicotinic receptor in the harmane effects on anxiety behavior has been evaluated. Materials and Methods: Mice were anesthetized with an intra-peritoneal injection of ketamine hydrochloride plus xylazine and then placed in a stereotaxic apparatus. Cannual were bilaterally implanted in the CA1 region of hippocampus. All animals were allowed to recover for 1 week before the beginning of the behavioral testing. The hole-board test was used to evaluate the anxiety-like behaviors. One-way analys was of variance so that Dunnett’s test was used to analyse data. All experiments were performed in accordance with institutional guidelines for animal care and use. Results: Intraperitoneal injection of harmane decreased the number of head dip and locomotion (P0.05). Conclusion: harmane and nicotine not only display anxiogenic effects but also demonstrate a complex interaction. The findings also indicated that harmane induces anxiety via non-nicotinic receptors

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