Lifelong dietary Omega-3, -6, and -9 ratios shape adult behavior and response to adolescent THC exposure in rats.
Ariel Frajerman, Aude Marzo, Boris Chaumette, Thérèse M. Jay, Fanny Demars, Antonin Lamazière, Oussama Kébir, Marie-Odile Krebs, Gwenaëlle Le Pen
Pharmacology, biochemistry, and behavior November 2025 DOI: 10.1016/j.pbb.2025.174086 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 164 |
| Population | Sprague Dawley rats, male and female, exposed from conception to specific diets and tested in adulthood |
| Interventions | Omega-3-enriched diet Delta-9-tetrahydrocannabinol (THC) |
| Duration | From conception through adulthood |
| Topics | Cannabis |
| Keywords | Brain maturation Cannabinoids Omega-3 Omega-6 Psychosis Schizophrenia |
| Key findings | Dietary enrichment with omega-3, omega-6, or omega-9 fatty acids significantly influenced adult rat social interactions, locomotor activity, anxiety, cognitive flexibility, response inhibition, and impulse control. Omega-3-fed rats were less anxious and more impulsive than omega-6-fed rats. Adolescent THC exposure interacted with diet and sex to affect adult anxiety and impulsivity. |
Abstract
Alterations in membrane lipids are well established in schizophrenia, and diet could be an accessible, modifiable etiological factor. We examined the influence of Polyunsaturated fatty acids (PUFAs) intake throughout the lifespan on behaviour in adult rats. We further explored a possible interaction with adolescent exposure to delta-9-tetrahydrocannabinol (THC), the lipidic psychoactive compound responsible for cannabis's psychotic effects. Sprague Dawley rats (n = 164, male and female) were separated into 3 groups exposed from conception to specific diets enriched in omega 3, 6, or 9, controlled by gas chromatography, with ratios determined to stay close to physiological balance. They were explored in adulthood in tests acknowledged as modelling symptomatic dimensions of schizophrenia, including locomotor activity, short-term recognition memory, sensorimotor gating, social interactions, anxiety, impulsivity, response inhibition and attention. The effects of diet on social interactions, locomotor activity, anxiety, cognitive flexibility, response inhibition, and impulse control were significant. Omega-3-enriched diet rats were less anxious and more impulsive than those receiving an omega-6 diet. THC exposure in adolescence interacts with diet and gender to influence adult anxiety and impulsivity. The diet's impacts are difficult to compare with previous data because we used new ratios of PUFA to be more physiological. These results underline the importance of considering the relative influence of the 3 different families of Unsaturated Fatty acids and the importance of the omega-6/omega-3 ratio in controlled and balanced diets. The results could explain why omega-3 supplementation has only a moderate effect at high dosages and/or possibly only in patients with an initial alteration in lipid membrane composition.