317. PSILOCYBIN DOES NOT INDUCE CONDITIONED PLACE PREFERENCE, BUT MODIFIES BEHAVIORAL PATTERNS IN SPRAGUE-DAWLEY RATS
Notice bibliographique
Résumé
Abstract Background Recent years have seen renewed scientific interest in psychedelics, including psilocybin, for their potential in treating neuropsychiatric disorders. However, the reward-related properties and behavioral impacts of a high dose of psilocybin remain insufficiently explored. Aims & Objectives Assessing the potential rewarding properties of a high dose of psilocybin (10 mg/kg i.p.) in the conditioned place preference (CPP) paradigm (McKendrick et al., Front. Behav. Neurosci., 2020) and analyze its effects on rat behavior. Method Twenty adult male Sprague Dawley rats (225–340 g) were subjected to CPP paradigm. On day 1, they were habituated to the apparatus, and on day 2, a preconditioning test assessed baseline compartment preference. Over 8 days, rats were conditioned (CT) by alternating between drug/vehicle conditioning on odd days (CT1,3,5,7) and vehicle conditioning on even days (CT2,4,6,8). After drug/vehicle administration, rats were confined to one CPP compartment. The potential rewarding effect of psilocybin was evaluated on the following day (postconditioning). Behavioral assessments, including head-twitch, dog-shaking, grooming, body licking, defecation, and rearing, were conducted during the CT sessions and on the postconditioning day. Results RM two-way ANOVA showed no significant difference in time spent in the psilocybin-paired compartment compared to vehicle, indicating that psilocybin did not produce rewarding effects in the CPP paradigm. Psilocybin administration led to modifications in the behavioral profile. Principal component analysis (explained variance>70%) indicated that head-twitching, dog-shaking, and defecation were more strongly associated with psilocybin, while grooming, body licking, and rearing were more characteristic of the vehicle group. For behavioral assessment, RM two-way ANOVA showed that on CT1, the psilocybin-treated group exhibited higher scores on head-twitching (p<0.0001), dog-shaking (p<0.05), and defecation (p<0.01), but lower scores on grooming (p<0.05), body licking (p<0.01), and rearing (p<0.01) compared to the vehicle group. These differences were even more pronounced on CT7 for head-twitching, dog-shaking, grooming, and body licking (p<0.0001), but not for rearing or defecation. Importantly, on the post-conditioning day (48 hours after the last psilocybin injection), the unpaired Student’s t-test revealed no behavioral differences. Discussion & Conclusions Our findings show that psilocybin is not linked to rewarding properties in the CPP paradigm. Psychedelics primarily act through serotonergic mechanisms, primarily via 5-HT2AR, with mild effects on 5-HT2CR. Activation of 5-HT2CR has been shown to mitigate drug craving and reduce dopamine-related reinforcing effects, suggesting a potential mechanism for their limited addiction liability (Canal et al., J Psychopharmacology, 2017).. Behavioral analysis revealed that psilocybin increased head-twitch and dog-shaking behaviors, key markers of psychedelic effects; but decreased grooming, rearing and body licking behaviors, which could reflect anxiolytic/anti-repetitive effects. No long-term behavioral changes were found, aligning with evidence that psychedelics do not cause physical dependence or withdrawal symptoms. These findings support the safety profile of psilocybin and its therapeutic potential, even if more studying assessing reward (i.e. self administration) should be conducted.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».