Beta-amyloid treatment sensitizes mice to amphetamine-induced locomotion but reduces response to caffeine

Psychosis frequently occurs in Alzheimer's disease (AD), being associated with more severe cognitive decline, but the underlying mechanisms are unknown.

To investigate the effect of centrally administered beta-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.

Mice were intracerebroventricularly injected with beta-amyloid (25-35), and after 1 week they were tested in the passive avoidance, spontaneous alternation and locomotor tasks.

Besides impaired performance in inhibitory avoidance and spontaneous alternation tasks, beta-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.

These results are compatible with the hypothesis that beta-amyloid peptide may predispose to psychotic symptoms of AD by increasing sensitivity of the dopaminergic system, possibly related to a decreased adenosinergic inhibitory tone.