Neurobiology of learning and memory
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Neurobiol Learn Mem · Sep 2011
Two novel 5-HT6 receptor antagonists ameliorate scopolamine-induced memory deficits in the object recognition and object location tasks in Wistar rats.
The 5-hydroxytryptamine(6) (5-HT(6)) receptor has been suggested to play an important role in the regulation of memory and cognition. In the present study, our aim was to investigate whether the novel, selective 5-HT(6) antagonists compound (CMP) X and CMP Y and the reference 5-HT(6) antagonist GSK-742457 could ameliorate impairments in episodic memory in 3-months-old male Wistar rats. The acetylcholinesterase inhibitor (AChEI) donepezil (Aricept®, approved for symptomatic treatment of Alzheimer's disease, AD) was used as a positive reference compound. ⋯ In conclusion, the 5-HT(6) antagonists were found to clearly improve episodic memory deficits induced by scopolamine. In addition, co-administration of the 5-HT(6) receptor antagonists CMP X and CMP Y with the AChEI donepezil to cognitively impaired rats also resulted in potentially additive enhancing effects on cognition. This suggests that these compounds could have potential as monotherapy, but also as adjunctive therapy in patients with AD treated with common treatments such as donepezil.
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Neurobiol Learn Mem · Sep 2011
Role of amygdala-prefrontal cortex circuitry in regulating the expression of contextual fear memory.
The basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) are inter-connected regions involved in fear memory expression. The reciprocal nature of projections between these areas differs along the rostrocaudal extent of BLA. This study investigated the role of functional interactions between BLA and the prelimbic (PL) subregion of mPFC in mediating contextual fear memory. ⋯ Bupivacaine infusion did not affect behavior in the open field, likely ruling out non-specific effects of inactivation on innate fear and locomotor activity. These results demonstrate different roles for rostral and caudal BLA in mediating the expression of contextual fear memory. They also raise the possibility that pBLA-PL circuitry is involved in subserving fear memory expression via complex processing mechanisms, although further research is needed to confirm this preliminary finding.
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Neurobiol Learn Mem · Sep 2011
Gami-Chunghyuldan ameliorates memory impairment and neurodegeneration induced by intrahippocampal Aβ 1-42 oligomer injection.
Soluble oligomeric forms of amyloid beta (AβO) are regarded as a main cause of synaptic and cognitive dysfunction in Alzheimer's disease (AD) and have been a primary target in the development of drug treatments for AD. The present study utilized a mouse model of AD induced by intrahippocampal injection of AβO (10 μM) to investigate the effects of Gami-Chunghyuldan (GCD), a standardized multi-herbal medicinal formula, on the presentation of memory deficits and neurohistological pathogenesis. ⋯ In addition, GCD prevented AβO-triggered synaptic disruption and cholinergic fiber loss. These results suggest that GCD may be useful in the prevention and treatment of AD.
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Neurobiol Learn Mem · Sep 2011
Activation of cannabinoid CB1 receptors in the central amygdala impairs inhibitory avoidance memory consolidation via NMDA receptors.
In the present study, we investigated the influence of bilateral intra-central amygdala (intra-CeA) microinjections of N-methyl-D-aspartate (NMDA) receptor agents on amnesia induced by a cannabinoid CB1 receptor agonist, arachydonilcyclopropylamide (ACPA). This study used a step-through inhibitory (passive) avoidance task to assess memory in adult male Wistar rats. The results showed that intra-CeA administration of ACPA (2 ng/rat) immediately after training 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. ⋯ Although post-training intra-CeA administration of the NMDA receptor antagonist, D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5; 0.01, 0.05 and 0.1 μg/rat) alone had no effect, its co-administration with an ineffective dose of ACPA (1 ng/rat) impaired IA memory consolidation. Post-training intra-CeA microinjection of an ineffective dose of D-AP5 (0.01 μg/rat) prevented an NMDA response to the impaired effect of ACPA. These results suggest that amnesia induced by intra-CeA administration of ACPA is at least partly mediated through an NMDA receptor mechanism in the Ce-A.