Adenosine has been proposed to contribute to the pathophysiology of schizoprenia and as a target for therapeutic intervention. In the lack of direct adenosine agonists, allopurinol may indirectly elevate adenosine levels by inhibiting degradation of purines. We report two cases of poorly responsive schizophrenic patients who improved considerably with add-on allopurinol 300 mg/day. Their clear clinical improvement warrant further investigation of allopurinol, as well as other purinergic strategies, for the treatment of schizophrenia.

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.