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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Dall'Igna
Oscar P
OP
Departamento de Bioquímica, Instituto de Ciencias Basicas da Saude, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. oscar.dalligna@ufrgs.br
Hoffmann
Anselmo
A
da Silva
Adriana L
AL
Souza
Diogo O
DO
Lara
Diogo R
DR
D000241:Adenosine / Q000378:metabolism; D018663:Adrenergic Agents / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000150:complications / Q000503:physiopathology; D000661:Amphetamine / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005973:Glutamine / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D011618:Psychotic Disorders / Q000209:etiology / Q000503:physiopathology
D018663:Adrenergic Agents; D016229:Amyloid beta-Peptides; D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D005973:Glutamine; D002110:Caffeine; D016291:Dizocilpine Maleate; D000661:Amphetamine; D000241:Adenosine; D004298:Dopamine