Western Diet Chow Consumption in Rats Induces Striatal Neuronal Activation While Reducing Dopamine Levels without Affecting Spatial Memory in the Radial Arm Maze.

Rats fed high fat diets have been shown to be impaired in hippocampal-dependent behavioral tasks, such as spatial recognition in the Y-maze and reference memory in the Morris water maze (MWM). It is clear from previous studies, however, that motivation and reward factor into the memory deficits associated with obesity and high-fat diet consumption, and that the prefrontal cortex and striatum and neurotransmitter dopamine play important roles in cognitive performance. In this series of studies we extend our research to investigate the effect of a high fat diet on striatal neurochemistry and performance in the delayed spatial win-shift radial arm maze task, a paradigm highly reliant on dopamine-rich brain regions, such as the striatum after high fat diet consumption. Memory performance, neuronal activation and brain dopaminergic levels were compared in rats fed a "Western" (21% fat, 0.15% cholesterol) chow diet compared to normal diet (6% fat, 0.15% cholesterol)-fed controls. Twelve weeks of dietary manipulation produced an increase in weight in western diet-fed rats, but did not affect learning and performance in the delayed spatial win-shift radial arm maze task. Concurrently, there was an observed decrease in dopamine levels in the striatum and a reduction of dopamine turnover in the hippocampus in western diet-fed rats. In a separate cohort of rats Fos levels were measured after rats had been placed in a novel arena and allowed to explore freely. In normal rats, this exposure to a unique environment did not affect neuronal activation. In contrast, rats fed a western diet were found to have significantly increased Fos expression in the striatum, but not prefrontal cortex or hippocampus. Our study demonstrates that while western diet consumption in rats produces weight gain and brain neuronal and neurotransmitter changes, it did not affect performance in the delayed spatial win-shift paradigm in the radial arm maze. We conclude that modeling the cognitive decline-obesity relationship is complex with considerations, of type of memory, behavioral task and dietary intervention (fat, fat and sugar, sugar, and cafeteria diets) all adding to our overall understanding.

Obesity and cognitive decline: role of inflammation and vascular changes.

The incidence of obesity in middle age is increasing markedly, and in parallel the prevalence of metabolic disorders including cardiovascular disease and type II diabetes is also rising. Numerous studies have demonstrated that both obesity and metabolic disorders are associated with poorer cognitive performance, cognitive decline, and dementia. In this review we discuss the effects of obesity on cognitive performance, including both clinical and preclinical observations, and discuss some of the potential mechanisms involved, namely inflammation and vascular and metabolic alterations.

Effect of low-intensity treadmill exercise on behavioural measures and hippocampal parvalbumin immunoreactivity in the rat.

Exercise has been demonstrated to have positive effects on both the body and brain. The present study aimed to determine the behavioural and morphological consequence of low-intensity running. Rats were exercised on a treadmill for a total of 30 days, 30 min/day. Social interaction, locomotor activity and behaviour on an elevated plus maze were assessed post-treatment. Exercised animals demonstrated more passive interaction and less time not interacting than control animals that were not exercised. Conversely, locomotor and anxiety measures showed no effect of exercise. Analysis of brains demonstrated an increase in expression of parvalbumin immunoreactive neurons in the hippocampus localised to the CA1 and CA2/3 regions. These results demonstrate that low-intensity exercise leads to changes in social behaviour as well as neuroplastic morphological changes within the hippocampus.

The basolateral amygdala is critical for learning about neutral stimuli in the presence of danger, and the perirhinal cortex is critical in the absence of danger.

The perirhinal cortex (PRh) and basolateral amygdala (BLA) appear to mediate distinct aspects of learning and memory. Here, we used rats to investigate the involvement of the PRh and BLA in acquisition and extinction of associations between two different environmental stimuli (e.g., a tone and a light) in higher-order conditioning. When both stimuli were neutral, infusion of the GABAA, muscimol, or the NMDA receptor (NMDAR) antagonist ifenprodil into the PRh impaired associative formation. However, when one stimulus was neutral and the other was a learned danger signal, acquisition and extinction of the association between them was unaffected by manipulations targeting the PRh. Temporary inactivation of the BLA had the opposite effect: formation and extinction of an association between two stimuli was spared when both stimuli were neutral, but impaired when one stimulus was a learned danger signal. Subsequent experiments showed that the experience of fear per se shifts processing of an association between neutral stimuli from the PRh to the BLA. When training was conducted in a dangerous environment, formation and extinction of an association between neutral stimuli was impaired by BLA inactivation or NMDAR blockade in this region, but was unaffected by PRh inactivation. These double dissociations in the roles of the PRh and BLA in learning under different stimulus and environmental conditions imply that fear-induced activation of the amygdala changes how the brain processes sensory stimuli. Harmless stimuli are treated as potentially harmful, resulting in a shift from cortical to subcortical processing in the BLA.

Effect of western and high fat diets on memory and cholinergic measures in the rat.

Recent evidence shows an association between obesity and cognitive decline. The present study aimed to determine whether a very high fat (60%) or western diet can affect working or spatial memory in rats and whether the diet-induced cognitive impairment is linked to the level of acetylcholine in the brain. Three groups of male Long Evans rats were fed either chow, western diet (21% fat, 0.15% cholesterol) or a high fat diet (60% fat) for 12 weeks (n=12 per group). Body weight, food intake and blood pressure were measured weekly. Behavioural testing, novel object recognition and Y-maze were carried out at 12 weeks. At the end of the study brain choline acetyltransferase and acetylcholinesterase levels were estimated. Results showed that consumption of a western diet for twelve weeks impaired a rat's spatial memory (p<0.05), and increased body weight, calorie intake, blood pressure and triglyceride levels. Conversely our high fat diet also impaired spatial memory (p<0.05) but this effect was independent of the rat's body weight or blood pressure. No significant changes in brain acetylcholine markers were observed. In conclusion, diets with higher fat content impaired hippocampal-dependant memory, even when hypertension and obesity are absent; however the mechanism is still unclear.

Lesions of the prelimbic prefrontal cortex prevent response conflict produced by action-outcome associations.

Rats with prelimbic (PL) cortex lesions were tested on a discrete-trial discrimination where food rewards were used as both discriminative cues and reinforcing outcomes. On incongruent trials, the discriminative cue food differed from the outcome food; on congruent trials they were the same. When cue and outcome foods differ, a conflict is created between the response directly promoted by the food as a cue (mediated by stimulus-response, S-R, associations) and the response indirectly promoted by the food as an outcome (mediated via action-outcome associations). No conflict is produced when cue and outcome foods are the same. Sham-lesioned rats acquired the discrimination more slowly for incongruent trials than for congruent trials, and incongruent trials were more susceptible to disruption by delay. In contrast there was no difference between congruent and incongruent trial types in PL-lesioned animals during acquisition or delay testing. Delays between cue and response had greater overall effects on lesioned than on sham-lesioned animals. These results are consistent with the behaviour of PL-lesioned animals being controlled by S-R associations with no response conflict due to interference from action-outcome associations.

Dopamine activity in the nucleus accumbens modulates blocking in fear conditioning.

Associative learning depends on the discrepancy between actual and predicted outcomes. The neurochemical mechanisms involved in regulating this discrepancy in Pavlovian fear conditioning in rats are unknown. We employed the blocking paradigm to show that this learning discrepancy is decreased by heightened activation of dopamine following an accumbal infusion of d-amphetamine, and increased by dopaminegic blockade following an accumbal infusion of cis-(z)-flupenthixol or by combined infusions of the D1 (SCH23390) and D2 (sulpiride) antagonists but not by infusion of either alone.

The effect of lesions of the basolateral amygdala on instrumental conditioning.

In three experiments, we assessed the effect of lesions of the amygdala basolateral complex (BLA) on instrumental conditioning in rats. In experiment 1, the lesion had no effect on the acquisition of either lever pressing or chain pulling in food-deprived rats whether these actions earned food pellets or a maltodextrin solution. The lesion did attenuate, however, the impact of outcome devaluation, induced by sensory-specific satiety, on instrumental performance both when assessed in extinction and when reward was delivered contingent on instrumental performance. In experiment 2, evidence was found to suggest that the lesioned rats differed from shams in their ability to encode the specific action-outcome contingencies to which they were exposed during training: lesioned rats failed to adjust their performance appropriately when the action-outcome contingency was degraded. These effects were not caused by an inability of BLA lesioned rats to discriminate the two instrumental actions; these rats were similar to shams in their acquisition of a heterogeneous instrumental chain involving lever pressing and chain pulling (experiment 3). In experiment 4, however, lesions of the BLA were found to produce a deficit in the ability of rats to use the specific properties of the instrumental outcomes used in the previous experiments to discriminate rewarded from unrewarded actions in a free operant discrimination situation. Together these results suggest that in instrumental conditioning, the BLA mediates outcome encoding, specifically relating the sensory features of nutritive commodities to the emotional consequences induced by their consumption.