Behavioural brain research
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Cognitive deficits are a major clinical unmet need in schizophrenia. The psychotomimetic drug phencyclidine (PCP) is widely applied in rodents to mimic symptoms of schizophrenia, including cognitive deficits. Previous studies have shown that sub-chronic PCP induces an enduring episodic memory deficit in female Lister Hooded rats in the novel object recognition (NOR) task. ⋯ Female Lister hooded rats were treated sub-chronically with either vehicle (0.9% saline) or PCP (2mg/kg two doses per day for 7 days), followed by a 7 days washout period. 30 min prior to the acquisition trial of the NOR task animals were dosed with either vehicle, CX546 (10, 40 or 80 mg/kg) or CX516 (0.5, 2.5, 10, 40 or 80 mg/kg). Our results show that sub-chronic PCP treatment induced a significant decrease in the discrimination index (DI) and both ampakines CX546 and CX516 were able to reverse this disruption of object memory in rats in the novel object recognition task. These data suggest that positive AMPAR modulation may represent a mechanism for treatment of cognitive deficits in schizophrenia.
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Co-infusion of ultra-low dose naloxone and morphine attenuates morphine tolerance through the prevention of mu opioid receptor-Gs protein coupling. We previously demonstrated that chronic intrathecal infusion of morphine leads to tolerance and spinal neuroinflammation. The aim of present study was to examine the possible mechanisms by which ultra-low dose naloxone modulates spinal neuroinflammation, particularly the role of anti-inflammatory cytokine interleukin 10 (IL-10). ⋯ The increase of IL-10 protein and mRNA were 1.5- and 3-fold, respectively, compared to that in morphine-infused rat spinal cords. A combination of daily rrIL-10 (1 microg) injection with morphine infusion produced, in a less potent, preservative antinociception and inhibited pro-inflammatory cytokine production compared to ultra-low dose naloxone co-infusion, and the effect of ultra-low dose naloxone co-infusion was inhibited by daily intrathecal anti-rat IL-10 antibody injection. These results demonstrate that IL-10 contributes to the attenuation of pro-inflammatory cytokine expression caused by ultra-low dose naloxone/morphine co-infusion and thus the attenuation of morphine tolerance.
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Nitric oxide (NO) is sought to be an intracellular messenger in the central nervous system and its implication in learning and memory is well documented. Compounds that inhibit nitric oxide synthase (NOS), the key synthesizing enzyme, block cognition, though discrepant findings, in this context, have also been reported. The present study was designed to investigate in the rat: (a) the effects on recognition memory exerted by low doses of the NOS inhibitor L-NAME and (b) the ability of this compound in modulating different mnemonic processes (acquisition, storage and retrieval). ⋯ In a first study, pre- or post-training systemic administration of L-NAME (1, 3 and 10mg/kg, i.p.) did not disrupt animals' performance in this recognition memory paradigm. Subsequently, L-NAME (1 and 3, but not 10mg/kg, i.p.) antagonized delay-dependent deficits in the object recognition task suggesting that L-NAME affected acquisition, storage and retrieval of information. These results indicate that the NOS inhibitor L-NAME may modulate different aspects of memory.