Abstract
The involvement of the serotonin system in the pathophysiology of schizophrenia has been elucidated by experiments with hallucinogens. Application of a hallucinogen to humans leads to changes in perception, cognition, emotions, and induction of psychotic-like symptoms that resemble symptoms of schizophrenia. In rodent studies, their acute administration affects sensorimotor gating, locomotor activity, social behavior, and cognition including working memory, the phenotypes are considered as an animal model of schizophrenia. The complexity and singularity of human cognition raises questions about the validity of animal models utilizing agonists of 5-HT2A receptors. The present study thus investigated the effect of psilocin on memory acquisition, reinforced retrieval, and memory consolidation in rats. Psilocin is a main metabolite of psilocybin acting as an agonist at 5-HT2A receptors with a contribution of 5-HT2C and 5-HT1A receptors. First, we tested the effect of psilocin on the acquisition of a Carousel maze, a spatial task requiring navigation using distal cues, attention, and cognitive coordination. Psilocin significantly impaired the acquisition of the Carousel maze at both doses (1 and 4 mg/kg). The higher dose of psilocin blocked the learning processes even in an additional session when the rats received only saline. Next, we examined the effect of psilocin on reinforced retrieval and consolidation in the Morris water maze (MWM). The dose of 4 mg/kg disrupted reinforced retrieval in the MWM. However, the application of a lower dose was without any significant effect. Finally, neither the low nor high dose of psilocin injected post-training caused a deficit in memory consolidation in the MWM. Taken together, the psilocin dose dependently impaired the acquisition of the Carousel maze and reinforced retrieval in MWM; however, it had no effect on memory consolidation.
Highlights
Psilocybin (O-phosphoryl-4-hydroxy-N,N -dimethyltryptamine) and its active metabolite psilocin (4-hydroxy-N,N -dimethyltrypt amine) are the main psychoactive indolealkylamines contained in hallucinogenic mushrooms (Hasler et al, 1997; Passie et al, 2002; Tyls et al, 2013)
These results show that www.frontiersin.org a dose of 4 mg/kg of psilocin induced a decrease in locomotor activity but the locomotion of this group still increased with the training
These results show that the dose of 4 mg/kg of psilocin impaired locomotor activity in the Carousel maze, whilst the dose of 1 mg/kg did not affect it
Summary
Psilocybin (O-phosphoryl-4-hydroxy-N,N -dimethyltryptamine) and its active metabolite psilocin (4-hydroxy-N,N -dimethyltrypt amine) are the main psychoactive indolealkylamines contained in hallucinogenic mushrooms (Hasler et al, 1997; Passie et al, 2002; Tyls et al, 2013). Psilocybin attenuates neurocognitive parameters in humans (e.g., disrupted sustained attention and altered visual information processing) and disrupts sensorimotor processing (Tyls et al, 2013), effects that are typically disrupted in psychotic patients (Park and Holzman, 1992; Vollenweider et al, 1997, 1998; Geyer, 1998) Due to this phenomenological resemblance of acute intoxication with psychosis and its long history of safe clinical use (including psychiatric treatment) it is, nowadays, the most frequently used serotonergic model of psychosis in humans (Tyls et al, 2013). Despite the evidence of how psilocybin changes cognitive performance in humans, little is known about its effects on cognition in animals
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