Previous findings indicate that the acquisition and consolidation of recognition memory involves dopaminergic activity. Although dopamine deregulation has been observed in Alzheimer's disease (AD) patients, the dysfunction of this neurotransmitter has not been investigated in animal models of AD. The aim of this study was to assess, by in vivo microdialysis, cortical and hippocampal dopamine, norepinephrine, and glutamate release during the acquisition of object recognition memory (ORM) in 5-and 10-mo-old triple-transgenic Alzheimer's disease mice (3xTg-AD) and to relate the extracellular changes to 24-h memory performance. Five-and 10-mo-old wild-type mice and 5-mo-old 3xTg-AD showed significant cortical but not hippocampal dopamine increase during object exploration. On a 24-h ORM test, these three groups displayed significant ORM. In contrast, 10-mo-old 3xTg-AD mice showed impaired dopamine release in the insular cortex during ORM acquisition, as well as significant impairment in ORM. In addition, cortical administration of a dopamine reuptake blocker produced an increase of dopamine levels in the 10-mo-old 3xTg-AD mice and attenuated the memory impairment. These data suggest that activation of the dopaminergic system in the insular cortex is involved in object recognition memory, and that dysfunction of this system contributes to the age-related decline in cognitive functioning of the 3xTg-AD mice.Alzheimer's disease (AD) is an age-related and progressive degenerative disorder generally characterized by two neuropathological features: deposits of amyloid-beta (Ab) peptides and neurofibrillary tangles, formed by the hyperphosphorylated microtubulebinding protein tau (Selkoe 2001). These neuropathological features are generally prominent in learning and memory-related brain regions, including the hippocampus, amygdala, and neocortex (Braak and Braak 1991;Nicholson et al. 2010). Because these pathologies are related to synaptic dysfunction leading to neurotransmitter deregulation including acetylcholine deficiency (Davis et al. 1999), several pharmacological therapies for AD focus on the restoration or modulation of cholinergic neurotransmission by acetylcholinesterase inhibitors and muscarinic agonists (Caccamo et al. 2009;Galluzzi et al. 2010). However, there is also evidence that these treatments may increase extracellular levels of dopamine (DA) (Shearman et al. 2006;Preda et al. 2008), suggesting that DA increase may contribute to the therapeutic effect. The possibility that the dopaminergic system may be involved in AD is suggested by evidence of decreased DA levels assessed in post-mortem brain tissue of AD patients (Winblad et al. 1985;Nazarali and Reynolds 1992;Storga et al. 1996), as well as changes in DA receptor distribution and density in several brain structures of the temporal lobe (Joyce et al. 1993(Joyce et al. , 1998Kemppainen et al. 2003;Kumar and Patel 2007).Transgenic models of AD are widely used to study the role of Ab accumulation and tau tangles in the cognitive alterations characteristi...

It has been postulated that memory consolidation process requires post-learning molecular changes that will support long-term experiences. In the present study, we assessed with in vivo microdialysis and capillary electrophoresis whether such changes involve the release of neurotransmitters at post-acquisition stages. Using conditioned taste aversion paradigm we observed spontaneous off-line (i.e. in absence of stimulation) dopamine and glutamate reactivation within the insular cortex about 45 min after the stimuli association. These increments did not appear in control groups that were unable to acquire the task, and it seems to be dependent on amygdala activity since its reversible inactivation by tetrodotoxin impaired cortical off-line release of both neurotransmitters and memory consolidation. In addition, blockade of dopaminergic D1 and/or NMDA receptors before the off-line activity impaired long-but not short-term memory. These results suggest that off-line extracellular increments of glutamate and dopamine have a significant functional role in consolidation of taste memory.

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Neural plasticity is an intrinsic and essential characteristic of the nervous system that allows animals “self-tuning” to adapt to their environment over their lifetime. Activity-dependent synaptic plasticity in the central nervous system is a form of neural plasticity that underlies learning and memory formation, as well as long-lasting, environmentally-induced maladaptive behaviors, such as drug addiction and overeating of palatable hyper-caloric (PHc) food. In western societies, the abundance of PHc foods has caused a dramatic increase in the incidence of overweight/obesity and related disorders. To this regard, it has been suggested that increased adiposity may be caused at least in part by behavioral changes in the affected individuals that are induced by the chronic consumption of PHc foods; some authors have even drawn attention to the similarity that exists between over-indulgent eating and drug addiction. Long-term misuse of certain dietary components has also been linked to chronic neuroimmune maladaptation that may predispose individuals to neurodegenerative conditions such as Alzheimer’s disease. In this review article, we discuss recent evidence that shows how consumption of PHc food can cause maladaptive neural plasticity that converts short-term ingestive drives into compulsive behaviors. We also discuss the neural mechanisms of how chronic consumption of PHc foods may alter brain function and lead to cognitive impairments, focusing on prenatal, childhood and adolescence as vulnerable neurodevelopmental stages to dietary environmental insults. Finally, we outline a societal agenda for harnessing permissive obesogenic environments.

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