Ketamine-induced behavioural responses in an animal model for schizophrenia: new data after early inactivation of the prefrontal cortex - Archive ouverte HAL Accéder directement au contenu
Poster De Conférence Année : 2023

Ketamine-induced behavioural responses in an animal model for schizophrenia: new data after early inactivation of the prefrontal cortex

Résumé

Schizophrenia is a very complex and disabling neuropsychiatric disease, the aetiology of which still remains unknown. According to several recent proposals, the psychic disintegration characteristic of this disease would result from a defective connectivity between various integrative regions having a neurodevelopmental origin. Various abnormalities reminiscent of early brain development disturbances have been observed in the patients' left prefrontal cortex (PFC) [1]. In other respects, psychomimetic drugs such as the non-competitive NMDA/glutamate antagonist ketamine, can induce psychotic symptoms in healthy humans and exacerbate these symptoms in patients with schizophrenia. In the context of animal modelling of schizophrenia locomotor hyperactivity and repetitive behavioural responses induced by ketamine administration in rats are generally used to assess the validity of the considered model [2]. The present study was designed to precisely investigate the effects of ketamine in adult rats on behavioural responses, following a neonatal blockade of the left PFC (infralimbic/prelimbic region). During the neurodevelopmental period, impulse electrical activity appears to be crucial for shaping connections once developing axons reach the target structure. Therefore, functional inactivation of the left PFC was carried out by local Tetrodotoxin (TTX) microinjection in 8-day-old (PND8) rats. Then in adult male rats (11weeks), locomotor activity and repetitive behaviours (left and right rotation, head weaving, intense sniffing, self-grooming) were investigated after ketamine was administred sc with different doses (5mg/kg; 10mg/kg; 20mg/kg). Control animals receveid NaCl 0.9%. Behavioural changes were monitored using a small infrared-camera placed in the top of the experimental cage (24cm wide x 27 cm long x 44 cm high). The animals were given about one hour of habituation to the cage. Then, the animals received at random the sc injection of either NaCl 0.9% or one of the 3 doses of ketamine. The floor of the cage was divided into 4 virtual parts, all with the same surface area. To quantify locomotor activity, the number of times the animal moved from one quadrant to another (by engaging at least the head), as visually observed, was counted for 10-mins periods. The repetitive behaviours were measured as the time per 10-mins period spent in repetitive behaviour; rotation was defined as 4 consecutive 1/4 turns in the same direction. Behavioural parameters were analyzed before and after the ketamine administration. The main significant results obtained during 1 hour after sc injection of ketamine were the following : 1) A clear dose-effect was observed for the two conditions (PBS and TTX microinjected at PND8) for locomotor activity, left and right rotation, head-weaving+sniffing, and self-grooming ; 2) Increases in locomotor activity and left-rotation were more elevated in TTX animals compared to PBS animals. Results obtained with the two latter indexes strongly support the view that animals microinjected with TTX in the left PFC at PND8 present higher reactivity to ketamine, than PBS animals. To conclude, these findings may provide new insights for the animal modelling of the pathophysiology of schizophrenia, involving early functional disturbance of the prefrontal cortex. Acknowlegdments to N.Rusnac and Y.Usun for their help in experiments. REFERENCES: [1] N. M.J. van Veelen et al., Schizophrenia Research 123, 22–29 (2010) [2] M.A., Geyer. and B. Moghaddam, in Neuropsychopharmacology: The fifth generation of progress. 689-701 (2002)
Fichier non déposé

Dates et versions

hal-04165377 , version 1 (18-07-2023)

Identifiants

  • HAL Id : hal-04165377 , version 1

Citer

Séverine Heintz, Alain Louilot. Ketamine-induced behavioural responses in an animal model for schizophrenia: new data after early inactivation of the prefrontal cortex. CRBSDays-2023, Strasbourg, France, July 06-07, 2023, Jul 2023, Strasbourg, France. 2023. ⟨hal-04165377⟩

Collections

SITE-ALSACE
25 Consultations
0 Téléchargements

Partager

Gmail Facebook X LinkedIn More