Neurobiology of learning and memory
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Over the past several years, drug addiction has increasingly been accepted to be a disease of the brain as opposed to simply being due to a lack of willpower or personality flaw. Exposure to addictive substances has been shown to create enduring changes in brain structure and function that are thought to underlie the transition to addiction. Specific genetic and environmental vulnerability factors also influence the impact of drugs of abuse on the brain and can enhance the likelihood of becoming an addict. ⋯ Therefore, the addict's behavior becomes increasingly directed towards obtaining and using drugs of abuse, while at the same time developing a poorer ability to stop using, even when the drug is less rewarding or interferes with functioning in other facets of life. In this review we will discuss the clinical evidence that addicted individuals have altered learning and memory and describe the possible neural substrates of this dysfunction. In addition, we will explore the pre-clinical evidence that drugs of abuse cause a progressive disorder of learning and memory, review the molecular and neurobiological changes that may underlie this disorder, determine the genetic and environmental factors that may increase vulnerability to addiction, and suggest potential strategies for treating addiction through manipulations of learning and memory.
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Neurobiol Learn Mem · Oct 2011
Post-training intra-basolateral amygdala infusions of norepinephrine block sevoflurane-induced impairment of memory consolidation and activity-regulated cytoskeletal protein expression inhibition in rat hippocampus.
Considerable evidence indicates that the noradrenergic system of the basolateral amygdala (BLA) participates in the consolidation of various types of emotionally arousing memories. We previously reported that administration of an anesthetic-dose of sevoflurane immediately after continuous multiple-trail inhibition avoidance (CMIA) training impaired memory consolidation. This experiment investigated whether posttraining noradrenergic activation of the BLA is sufficient to reverse the memory impairing effect of sevoflurane. ⋯ Norepinephrine produced a dose-dependent enhancement of memory consolidation on a 24-h retention test. The highest dose of NE tested (3.0 μg/0.5 μl) blocked sevoflurane-induced impairment of memory consolidation and reversed the inhibitory effect of sevoflurane on activity-regulated cytoskeletal protein (Arc) expression in the hippocampus 2h after training. These findings provide evidence that the mechanism mediating the memory-impairing effect of sevoflurane involves a network interaction between the BLA noradrenergic system and modulation of Arc protein expression in the hippocampus.
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Neurobiol Learn Mem · Oct 2011
Voluntary exercise ameliorates cognitive deficits in morphine dependent rats: the role of hippocampal brain-derived neurotrophic factor.
Chronic exposure to opiates impairs spatial learning and memory. Given the well-known beneficial effects of voluntary exercise on cognitive functions, we investigated whether voluntary exercise would ameliorate the cognitive deficits that are induced by morphine dependence. If an effect of exercise was observed, we aimed to investigate the possible role of hippocampal brain-derived neurotrophic factor (BDNF) in the exercise-induced enhancement of learning and memory in morphine-dependent rats. ⋯ Moreover, the voluntary exercise diminished the severity of the rats' dependency on morphine. This study demonstrates that voluntary exercise ameliorates, via a TrkB-mediated mechanism, the cognitive deficits that are induced by chronic morphine. Thus, voluntary exercise might be a potential method to ameliorate some of the deleterious behavioral consequences of the abuse of morphine and other opiates.
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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.