Behavioural brain research
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In the present study, the effects of subcutaneous (s.c.) injections of morphine, a mu-opioid receptor agonist and intra-dorsal hippocampal (intra-CA1) injections of naloxone, a mu-opioid receptor antagonist on muscimol 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-CA1 administration of a GABAA receptor agonist, muscimol (0.025, 0.05, 0.1 and 0.2 microg/mouse) dose dependently induced impairment of memory retention. ⋯ Pre-test intra-CA1 injection of naloxone (0.1 and 0.2 microg/mouse, intra-CA1) improved pre-training muscimol (0.1 microg/mouse)-induced retrieval impairment. Moreover, pre-test administration of naloxone (0.1 and 0.2 microg/mouse, intra-CA1) with an ineffective dose of muscimol (0.025 microg/mouse) significantly restored the retrieval and induced muscimol state-dependent memory. These findings implicate the involvement of a dorsal hippocampal mu-opioid receptor mechanism in muscimol state-dependent memory.
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Comparative Study
Alterations of NR2B and PSD-95 expression in hippocampus of kainic acid-exposed rats with behavioural deficits.
Temporal lobe epilepsy (TLE), characterized by spontaneous recurrent seizure (SRS), is associated with behavioural problems, but the underlying molecular mechanisms have not been clearly identified. In the present study, kainic acid (KA) was administered systemically in adult male Wistar rats to induce SRS. Behavioural performance analyses at 2, 4, and 6 weeks post-status epilepticus (post-SE) showed spatial learning memory deficit, anxiety and increased locomotor activity in rats with long-term SRS compared with rats without SRS after normal saline (NS) or KA-valproate (KA-VPA) treatment. ⋯ Furthermore, the decreased expression of NR2B and PSD-95 was correlated with the representatively behavioural deficit. These findings suggest that long-term SRS might decrease NR2B/PSD-95 expression in adult hippocampus and consequently cause behavioural deficits, including spatial learning memory deficit, anxiety and increased locomotor activity. Maintaining the expression of NR2B/PSD-95 might partially contribute to the normal behaviour in rats with long-term SRS.
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Memory impairment is considered to be one of the most prominent consequences of aging. Deterioration of memory begins in advance of old age in animals, including humans. Thus, it is extremely important to prevent memory decline for increasing healthy aging. ⋯ The efficacious effect of ginsenoside was manifested in the amelioration of memory impairment in aged mice by Morris water maze and step-down tests. Compared with aged control group, the plasticity-related proteins including phospho-N-methyl-d-aspartate receptor1 (NMDAR1), phospho-calcium-calmodulin dependent kinase II (CaMK II), phospho-PKA catalytic beta subunit (PKA Cbeta), phospho-cAMP-response element binding protein (CREB) and brain derived neurotrophic factor (BDNF) in hippocampus significantly increased in ginsenoside treated group. These findings suggest that ginsenoside is effective on the prevention of age-related memory impairment, and the up-regulation of plasticity-related proteins in hippocampus may be one of the mechanisms.
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Methotrexate (MTX) is a cytostatic agent used in adjuvant chemotherapy for treatment of breast cancer and is associated with cognitive impairment in a subgroup of patients. The aim of this paper is to test whether MTX can rapidly affect various brain structures resulting in decreased hippocampal cell proliferation and white matter damage. We also studied whether cell death occurs in the hippocampus following MTX. ⋯ In the Morris water maze, animals treated with MTX spent significantly less time in the correct quadrant compared to control animals during the probe trial which was performed 1 week after training and treatment. In contextual fear conditioning, animals treated with MTX showed significantly less freezing behavior compared to control animals, 4 weeks after training and treatment. These studies suggest that the negative effect of MTX on hippocampal cell proliferation and white matter density may be part of the mechanisms underlying the cognitive impairment observed as side effect after cytotoxic treatment in humans.