The Effect of Psilocin on Memory Acquisition, Retrieval, and Consolidation in the Rat

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.

Psilocybin lacks antidepressant-like effect in the Flinders Sensitive Line rat

“…The route of administration was chosen to ensure reliable absorption and high bioavailability. Doses were chosen based on the published literature with psilocybin in rats (Davis and Walters, 1977;Geyer et al, 1979;Rambousek et al, 2014;Tyls et al, 2016) and therapeutic human doses (Carhart-Harris et al, 2016;Griffiths et al, 2016;Ross et al, 2016) converted using an allometric scaling factor of 6.2 from humans to rats (Nair and Jacob, 2016) (psilocybin 25 mg/70 kg × 6.2 = 2.2 mg/kg). Based on rat pharmacokinetics (Saito et al, 2004), 3 h was chosen as the earliest time point for behavioural testing to ensure that any behavioural effects would be due to persistent changes and not to the acute effects of the drug.…”

Memory deficits with intact cognitive control in the methylazoxymethanol acetate (MAM) exposure model of neurodevelopmental insult

“…This task is sensitive to dysfunction of multiple brain areas including dorsal hippocampus (Cimadevilla, Wesierska, Fenton, & Bures, 2001), basolateral amygdala (Serrano et al, 2008), retrosplenial cortex (Wesierska, Adamska, & Malinowska, 2009) and detects selective adult cognitive control deficits after neonatal ventral hippocampal lesion (NVHL), another schizophrenia-relevant rat model of a neurodevelopmental insult (Lee et al, 2012; O’Reilly, Kao, Lee, and Fenton, 2014). Task performance is also sensitive to psychotomimetics such as the NMDA receptor antagonist MK-801 (Stuchlik & Vales, 2005) and the hallucinogen psilocin (Rambousek, Palenicek, Vales, & Stuchlik, 2014).…”

Cognitive Deficits in Schizophrenia and Other Neuropsychiatric Disorders: Convergence of Preclinical and Clinical Evidence

“…A totally different serotonergic model of schizophrenia is presented by Rambousek et al ( 2014 ). The study shows effects of psilocin, an active serotonergic hallucinogen of Psylocibe mushrooms, on the acquisition, retrieval, and consolidation of memory in two spatial navigation tasks.…”