β-Amyloid Treatment Sensitizes Mice to Amphetamine-Induced Locomotion but Reduces Response to Caffeine

Backgroud: Psychosis frequently occurs in Alzheimer’s disease (AD), being associated with more severe cognitive decline, but the underlying mechanisms are unknown. Objective: To investigate the effect of centrally administered β-amyloid peptide, a model for AD, in the locomotor response to amphetamine, caffeine and MK-801, which are psychoactive drugs related to neurochemical changes occurring in psychosis. Methods: Mice were intracerebroventricularly injected with β-amyloid (25–35), and after 1 week they were tested in the passive avoidance, spontaneous alternation and locomotor tasks. Results: Besides impaired performance in inhibitory avoidance and spontaneous alternation tasks, β-amyloid-treated mice showed increased spontaneous locomotion, augmented response to amphetamine (1.5 mg/kg), blunted response to caffeine (30 mg/kg) and no difference in MK-801 (0.25 mg/kg)-induced locomotor activation when compared to its respective control. Conclusion: These results are compatible with the hypothesis that β-amyloid peptide may predispose to psychotic symptoms of AD by increasing sensitivity of the dopaminergic system, possibly related to a decreased adenosinergic inhibitory tone.