Acquisition Of Water Maze Task Research Articles

Letrozole delays acquisition of water maze task in female BALB/c mice: Possible involvement of anxiety

Letrozole, an aromatase inhibitor preventing estrogen synthesis from testosterone, is used as an adjuvant therapy in estrogen receptor-positive breast cancer patients. However, like other aromatase inhibitors, it induces many side effects, including impaired cognition. Despite its negative effect in humans, results from animal models are inconsistent and suggest that letrozole can either impair or improve cognition. Here, we studied the effects of chronic letrozole treatment on cognitive behavior of adult female BALB/c mice, a relevant animal model for breast cancer studies, to develop an appropriate animal model aimed at testing therapies to mitigate side effects of letrozole. In Morris water maze, letrozole 0.1 mg/kg impaired reference learning and memory. Interestingly, most of the letrozole 0.1 mg/kg-treated mice were able to learn the new platform position in reversal training and performed similar to control mice in a reversal probe test. Results of the reversal test suggest that letrozole did not completely disrupt spatial navigation, but rather delayed acquisition of spatial information. The delay might be related to increased anxiety as suggested by increased thigmotactic behavior during the reference memory training. The learning impairment was water maze-specific since we did not observe impairment in other spatial tasks such as in Y-maze or object location test. In contrast, the dose of 0.3 mg/kg did not have effect on water maze learning and facilitated locomotor habituation and recognition in novel object recognition test. The current study shows that letrozole dose-dependently modulates behavioral response and that its effects are task-dependent.

Effects of St-587 and prazosin on water maze and passive avoidance performance of scopolamine-treated rats

The present experiments were designed to investigate whether the alpha-1 adrenergic and muscarinic cholinergic systems interact in the regulation of spatial navigation behavior in the Morris water maze test and passive avoidance performance. Pretraining administration of scopolamine, a muscarinic antagonist, markedly impaired the acquisition of water maze task (a hidden platform version) as well as retention of this task. The drug also impaired slightly navigation to a visible platform. Pretraining subcutaneous administration of St-587 (alpha-1 agonist) at 2000 μg/kg slightly improved the water maze navigation to a hidden platform in control rats, but its effect was not augmented in scopolamine-treated rats. Pretraining administration of prazosin (alpha-1 antagonist) 1000 μg/kg or 2000 μg/kg did not significantly potentiate the scopolamine (muscarinic cholinergic antagonist)-induced (doses 200 μg/kg and 100 μg/kg, pretraining intraperitoneal injection) deficit in water maze navigation. Pretraining administration of prazosin at doses 1000 μg/kg and 2000 μg/kg or St-587 at doses 1000 μg/kg and 2000 μg/kg did not have any significant influence on scopolamine-induced (200 μg/kg or 400 μg/kg) disruption in passive avoidance performance. These findings suggest that alpha-1 adrenergic mechanisms do not participate or are not the most important component of the noradrenergic system in the interaction between noradrenaline and muscarinic receptors in the modulation of learning and memory. The analysis of results indicates that activation of alpha-1 adrenoceptors might facilitate the acquisition of water maze task in its initial phase, for instance, switching from wall hugging strategy to an active exploration strategy. Furthermore, the present data suggest that muscarinic cholinergic blockade may affect both mnemonic and nonmnemonic processes in rats.

Spatial Learning and Noradrenaline Content in the Brain and Periphery of Young and Aged Rats

The present experiment studied whether a dysfunction of the noradrenergic neurons is related to spatial learning impairment by investigating the levels of noradrenaline in the brain and periphery as well as the acquisition of water maze task in saline-pretreated young rats, in noradrenergic neurotoxin (DSP-4)-pretreated young rats and in saline-pretreated aged rats. Aged rats, which had an increased escape latency onto the hidden platform, revealed a decreased noradrenaline content in the heart, but not in the hippocampus, striatum, or hypothalamus, whereas DSP-4-pretreated rats had decreased noradrenaline content in the brain; the acquisition of water maze task was not impaired. These results suggest that the peripheral noradrenergic system can show age-related changes different from those in the central noradrenergic system, and they failed to provide support for the hypothesis that decreased activity of the central noradrenergic nerves is related to impairment in the acquisition of the water maze task.