The effects of hallucinogenic drugs on maze exploration in the rat over a 24 hour period

Davies, John A.; Redfern, P. H.

doi:10.1111/j.1476-5381.1973.tb08274.x

Cited by 12 publications

(3 citation statements)

References 15 publications

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“…Similar findings to ours were shown for 2,5-dimethoxy-4-iodoamphetamine (DOI) in a special water maze, where this compound worsened the performance during acute intoxication as well as when subsequently tested without the influence of the drug (Kant et al, 1998). Early studies with LSD and mescaline congruently found disruption of spatial navigation, exploration, and discrimination within different frameworks in T-maze/Y-maze (Castellano, 1971; Davies and Redfern, 1973; Molinengo et al, 1986; Koupilova et al, 1989, 1999). LSD and other hallucinogens also induced errors in swimming through an underwater maze and increased starting latency of swimming through the maze (Uyeno, 1969, 1986).…”

Section: Discussionmentioning

confidence: 92%

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

Rambousek

Páleníček²,

Valeš

et al. 2014

Front. Behav. Neurosci.

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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.

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Section: Discussionmentioning

confidence: 92%

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

Rambousek

Páleníček²,

Valeš

et al. 2014

Front. Behav. Neurosci.

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“…Such a biphasic effect has also been described for other behavioural parameters induced by hallucinogens, especially locomotor activity (Davies and Redfern, 1973;Fantegrossi et al, 2008;Palenicek et al, 2008). The effect on wet dog shakes was also found in other studies where psilocin increased this particular behavioural pattern only up to a dose of 2.4 mg/kg (Vickers et al, 2001;.…”

Section: Females MD Females Pe Malesmentioning

confidence: 85%

Sex differences and serotonergic mechanisms in the behavioural effects of psilocin

Tylš

Páleníček

Kadeřábek

et al. 2016

Behavioural Pharmacology

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Psilocybin has recently attracted a great deal of attention as a clinical research and therapeutic tool. The aim of this paper is to bridge two major knowledge gaps regarding its behavioural pharmacology - sex differences and the underlying receptor mechanisms. We used psilocin (0.25, 1 and 4 mg/kg), an active metabolite of psilocybin, in two behavioural paradigms - the open-field test and prepulse inhibition (PPI) of the acoustic startle reaction. Sex differences were evaluated with respect to the phase of the female cycle. The contribution of serotonin receptors in the behavioural action was tested in male rats with selective serotonin receptor antagonists: 5-HT1A receptor antagonist (WAY100635 1 mg/kg), 5-HT2A receptor antagonist (MDL100907 0.5 mg/kg), 5-HT2B receptor antagonist (SB215505 1 mg/kg) and 5-HT2C receptor antagonist (SB242084 1 mg/kg). Psilocin induced dose-dependent inhibition of locomotion and suppression of normal behaviour in rats (behavioural serotonin syndrome, impaired PPI). The effects were more pronounced in male rats than in females. The inhibition of locomotion was normalized by 5-HT1A and 5-HT2B/C antagonists; however, PPI was not affected significantly by these antagonists. Our findings highlight an important issue of sex-specific reactions to psilocin and that apart from 5-HT2A-mediated effects 5-HT1A and 5-HT2C/B receptors also play an important role. These findings have implications for recent clinical trials.

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“…In humans, hallucinogens alter perception, cognition, and emotions, and induce psychotic‐like responses that resemble symptoms of schizophrenia. In rodents, hallucinogens affect sensorimotor gating, locomotor activity, social behavior, and cognitive behaviors including working memory (Castellano, ; Davies and Redfern, ; Hanks and Gonzalez‐Maeso, ). Serotonergic psychedelics may impair the integrity of goal‐directed behaviors that are guided by visual cues.…”

Section: Introductionmentioning

confidence: 99%

Effect of a hallucinogenic serotonin 5‐HT_2A receptor agonist on visually guided, hippocampal‐dependent spatial cognition in C57BL/6J mice

2017

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By acting on serotonin 5-HT receptors (5-HT Rs), serotonergic psychedelic drugs induce perceptual and visual hallucinations by increasing neuronal excitability and altering visual-evoked neuronal responses. The present study was designed to examine whether the perceptual alterations induced by a serotonergic psychedelic drug would affect the integrity of hippocampal-dependent, visually guided spatial cognition. phenylalkylamine hallucinogen TCB-2 is a selective agonist of 5-HT Rs. Mice received TCB-2 (1.0 mg kg , i.p.), and spatial behaviors and hippocampal electrophysiological responses were measured with water maze tasks and in vivo single-unit recording, respectively. TCB-2 did not affect visual cue approach behavior in the visible platform water maze, but increased the latency of trained mice to initiate goal-directed swimming during a probe test in the hidden platform Morris water maze, which could be prevented by 5-HT R antagonist MDL 11,939. Interestingly, TCB-2 did not affect the efficiency of the swim path or the proper use of distal visual cues during the probe test. Hippocampal place cell activity is considered to represent spatial and context-specific episodic memory. Systemic TCB-2 did not affect previously established place fields of CA1 neurons in mice exploring a familiar environment, or the remapping of place cells when the mice explored a novel environment. However, TCB-2 impaired the long-term stability of place fields for the novel environment initially encoded under the influence of TCB-2, which could be prevented by 5-HT R antagonist MDL 11,939. Our data indicate that hallucinogenic 5-HT R agonist delays the initiation of spatial search behavior, but does not impair the use of visual cues to guide goal-directed spatial behavior. Moreover, activation of 5-HT Rs does not impair the coding and retrieval of spatial information, but impairs the long-term stability of new formed place fields of CA1 neurons. © 2017 Wiley Periodicals, Inc.

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The effects of hallucinogenic drugs on maze exploration in the rat over a 24 hour period

Cited by 12 publications

References 15 publications

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

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

Sex differences and serotonergic mechanisms in the behavioural effects of psilocin

Effect of a hallucinogenic serotonin 5‐HT_2A receptor agonist on visually guided, hippocampal‐dependent spatial cognition in C57BL/6J mice

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The effects of hallucinogenic drugs on maze exploration in the rat over a 24 hour period

Cited by 12 publications

References 15 publications

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

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

Sex differences and serotonergic mechanisms in the behavioural effects of psilocin

Effect of a hallucinogenic serotonin 5‐HT2A receptor agonist on visually guided, hippocampal‐dependent spatial cognition in C57BL/6J mice

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Effect of a hallucinogenic serotonin 5‐HT_2A receptor agonist on visually guided, hippocampal‐dependent spatial cognition in C57BL/6J mice