RESUMEN
Ring-substituted phenethylamines are believed to induce psychedelic effects primarily by interacting with 5-hydroxytryptamine 2 (5-HT2A) receptors in the brain. We assessed the effect of the psychedelic substances 25H-NBOMe and 25H-NBOH on the depressive-like behavior of male adult rats. Naive Wistar rats were divided into groups to assess the effects of different doses (0.1 mg/kg, 1 mg/kg, and 3 mg/kg) of 25H-NBOMe and 25H-NBOH. The substances were administered intraperitoneally and the hallucinogenic properties were evaluated using the head twitch response test (HTR). Additionally, we assessed their locomotor activity in the open field test (OFT) and depressive-like behavior in the forced swimming test (FST). Our data demonstrated that all doses of synthetic psychedelic substances evaluated exhibited hallucinogenic effects. Interestingly, we observed that both 25H-NBOMe and 25H-NBOH produced a significantly greater motivation to escape in the FST, compared to the control group. Furthermore, we found no significant differences in locomotor activity during the OFT, except for the dose of 3 mg/kg, which induced a reduction in locomotion. This study provides new insights into a potential psychedelic substance, specifically by demonstrating the previously unknown antidepressant properties of a single dose of both 25H-NBOMe and 25H-NBOH. These findings contribute to the ongoing progress of experimental psychiatry toward developing safe and effective clinical practices in the field of psychedelics research.
Asunto(s)
Alucinógenos , Ratas , Masculino , Animales , Alucinógenos/farmacología , Ratas Wistar , Antidepresivos/farmacología , Fenetilaminas/farmacología , NataciónRESUMEN
AIMS: We assessed the influence of maternal overweight on the behavioral neurodevelopment of male and female offspring in prepubertal age by reducing the litter size. MAIN METHODS: To reduce litter size in Wistar rats, the offspring of generation 0 (G0) were culled for 12 pups (6 males and 6 females: normal litter, NL-G1) or 4 pups (2 males and 2 females: small litter, SL-G1). In G1 dams, overweight was characterized, maternal behavior and locomotor activity were assessed. At G2, we quantified the ultrasonic vocalizations in post-natal day 5 (PND5); we evaluated olfactory discrimination in the homing behavior test on PND13; and in PND28-32 (prepubertal age), we performed the following tests: social play behavior, hole board, object recognition, and open field. At the end of the experiments, hippocampus and prefrontal cortex were dissected to quantify the synaptophysin by western blotting. KEY FINDINGS: Our data demonstrated that a reduction in litter size was able to induce maternal overweight without altering the parameters related to overweight in the offspring. The SL-G2 offspring showed deficits in early social communication, olfactory discrimination, social play behavior, and the exploration of objects, in addition to increasing repetitive and stereotyped movements. There were also changes in the synaptophysin levels in the hippocampus and prefrontal cortex of the offspring from reduced litter dams. In conclusion, maternal overweight caused by litter reduction impairs behavioral neurodevelopment, inducing autism-like symptoms in the offspring. SIGNIFICANCE: This study alerts the public about the negative consequences of maternal overweight in the descendants.
Asunto(s)
Conducta Materna/fisiología , Trastornos del Neurodesarrollo/etiología , Sobrepeso/fisiopatología , Animales , Animales Recién Nacidos , Peso Corporal , Encéfalo/metabolismo , Femenino , Hipocampo/metabolismo , Tamaño de la Camada/fisiología , Masculino , Trastornos del Neurodesarrollo/fisiopatología , Fenómenos Fisiológicos de la Nutrición/fisiología , Embarazo , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Ratas , Ratas WistarRESUMEN
Several studies have investigated the effects of artificial litter size adjustment on offspring development. Social play behavior is important for neurobehavioral development and is impaired in several developmental psychiatric disorders. This study therefore investigated the effect of litter size on play behavior in adolescent rats. On postnatal day (PND) 2, litters were adjusted to a small litter (SL) size of 3 pups per dam or normal litter (NL) size of 12 pups per dam. Maternal behaviors scored daily during the first week of lactation (PND2-8) revealed that arched nursing and pup licking behaviors were increased in dams with SLs versus those with NLs. SL offspring exhibited accelerated weight gain and advanced development of physical landmarks and reflexes, possibly due to overnutrition. Social isolation lasting 3.5h prior to social play behavioral testing produced a higher frequency and duration of pouncing, pinning, sniffing, and grooming in both male and female offspring. However, male SL offspring exhibited a lower frequency of pouncing and pinning when compared with male NL offspring, while no litter size-dependent differences were observed in social behaviors unrelated to play (sniffing and grooming). These findings identify a possible sexually dimorphic influence of litter size in the development of social behavior. Given that social behaviors such as play behavior are vital for normal cognitive and social development, these findings have important implications for developmental and neuropsychiatric research.