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

Abstract

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.

Pimavanserin, a 5-HT2A receptor inverse agonist, reverses psychosis-like behaviors in a rodent model of Alzheimer’s disease

“…The data extend findings from a previous study that showed augmented amphetamine-induced activity in mice infused with Ab 25-35 (Dall'Igna et al, 2004), and suggest that the infusion of Ab 25-35 produced a behavioral phenotype that may be used to assess the potential antipsychotic efficacy of novel therapeutics targeting ADP. The data extend findings from a previous study that showed augmented amphetamine-induced activity in mice infused with Ab 25-35 (Dall'Igna et al, 2004), and suggest that the infusion of Ab 25-35 produced a behavioral phenotype that may be used to assess the potential antipsychotic efficacy of novel therapeutics targeting ADP.…”

“…Animal models, even those that recapitulate only some aspects of the human disorder, can be useful tools for the assessment of the potential therapeutic efficacy of novel therapeutics, but to date, only a relatively modest effort has been invested toward establishing an animal model of ADP (Dall'Igna et al, 2004). In the present study, to facilitate the evaluation of a potential new therapeutic approach for the treatment of ADP, we extended the initial efforts toward development of an animal model by characterizing psychosis-related behavioral endpoints in animals with an AD-like histopathology.…”

The Impact of Muscarinic Antagonism on Psychosis-Relevant Behaviors and Striatal [11C] Raclopride Binding in Tau Mouse Models of Alzheimer’s Disease

“…Cholinesterase inhibitors utilized in the cognitive treatment of AD have been shown to decrease the emergence of psychotic symptoms [ 43 , 44 , 45 ]. In the limited literature that exists on the use of pharmacology to model psychosis in AD, a psychotomimetic challenge in preclinical models has been accomplished with dopamine-promoting stimulants [ 12 , 15 , 46 ], rather than compounds that target the cholinergic system, as epidemiologic evidence would recommend. The antimuscarinic scopolamine has been used in AD, as an induction agent, in memory paradigms only [ 47 ], mimicking AD-like impairments in preclinical [ 48 ] and acute neurocognitive performance models of AD [ 49 ], but it has not previously been employed as an induction model of AD psychosis-relevant behaviors.…”