Maternal metformin (MT) treatment improves the metabolic phenotype of high-fat (HF) diet-exposed offspring, but its effect on offspring’s palatable food preference remains unclear. We assessed HF diet and sucrose preferences in adult offspring from Sprague–Dawley rat dams fed a control diet, an HF diet with or without MT treatment. Additionally, we measured the mRNA expression of sweet taste perception-related genes in taste buds and dopamine- and opioid-related genes in the central reward system. In adult males, maternal HF diet increased HF food preference and decreased dopamine-related gene expression in the reward system. Furthermore, maternal MT treatment decreased low-concentration sucrose preference, and reduced opioid-related gene expression in the reward system. Maternal HF diet elevated sweet taste perception-related gene expression in taste buds, while maternal MT treatment reversed these changes. In adult females, neither maternal HF diet nor MT treatment affected HF food preference. However, maternal HF diet decreased low-concentration sucrose preference and reduced the expression of sweet taste perception-related genes, while maternal MT treatment did not reverse it. At weaning, maternal MT treatment generally decreased dopamine- and opioid-related gene expression in the central reward system across both sexes. Notably, this early-life central reward transcriptional suppression persisted into adulthood in males but not in females. Our results indicate that maternal HF diet and MT treatment influence HF diet and low-concentration sucrose preferences in adult offspring in a sex-specific manner, which may be associated with altered gene expression in the central reward system and the peripheral taste perception pathways.
Methamphetamine (METH) is a potent stimulant drug that significantly alters the function of the central nervous system (CNS). METHS’s abuse may be linked with a variety of psychiatric disorders, primarily by affecting the reward system. Cannabidiol (CBD), a primary cannabinoid component of the Cannabis plant, has been shown to affect the reward system, suggesting it for modulating addictive behaviors. On the other hand, deep brain stimulation (DBS) of the nucleus accumbens (NAc), one of the most significant brain regions implicated in mediating rewards, is effective in alleviating drug-seeking behaviors. The present research aimed to evaluate the effects of low-frequency DBS, CBD, and a combination of both on the extinction and reinstatement of METH-induced conditioned place preference (CPP). CBD was injected into the lateral ventricle at doses of 2.5, 5, and 10 μg/5 μL, and low-frequency DBS (10 Hz, for 30 min) was administered to the NAc, both during the extinction phase. The results showed CBD (10 µg/5 µL) or DBS facilitated extinction. DBS decreased mean extinction latency but did not differ significantly from CBD (10 µg/5 µL) alone. The combination groups at all tested CBD doses showed reduced mean extinction latency compared with the control groups; only the 10 µg/5 µL combination group differed significantly from DBS alone. However, neither CBD (10 µg/5 µL) alone nor DBS altered the CPP score on the reinstatement day. Combination of DBS and CBD administration (at all doses) significantly decreased the CPP score on the reinstatement day. In conclusion, it can be suggested that CBD may be beneficial for alleviating METH-induced reinstatement in combination with DBS, while both alone had no effect.
Personality fundamentally shapes language processing, yet the neurocognitive mechanisms underlying this relationship remain poorly understood. Openness to experience (Openness), as measured by the NEO Five-Factor Inventory (NEO-FFI), has been associated with enhanced creativity and engagement with novel semantic information. This study examined how openness modulates the neural dynamics of semantic processing using event-related potentials (ERPs) during a semantic category verification task. Participants evaluated category relatedness across the four levels of semantic structure, including high typicality (HT), low typicality (LT), related violations (RV), and nonrelated violations (NRV). Neural responses exhibited the expected graded pattern, with N400 amplitudes becoming more negative as semantic relatedness decreased. Critically, higher Openness was associated with greater N400 differentiation between related and nonrelated violations, an effect uniquely predicted by Openness beyond the remaining four personality traits. Follow-up analyses revealed that this differentiation was primarily driven by enhanced N400 responses to nonrelated violations rather than by reduced responses to related violations. This pattern is inconsistent with a simple facilitation account in which higher Openness uniformly eases semantic processing. Instead, it suggests that Openness is associated with heightened sensitivity to semantic mismatch or more sustained semantic evaluation when incoming information is incompatible with an activated context. Behavioral performance was comparable across participants; the observed neural differences were not accompanied by detectable differences in task success. Together, these findings establish that Openness is systematically related to variation in the neural dynamics of semantic processing, while highlighting the need to clarify the underlying cognitive mechanisms and contributions of other individual differences.
Athletes have to cope with psychosocial and physiological stressors, requiring recovery to ensure subsequent performance. According to the undoing-hypothesis, positive emotions (PE) may enhance psychophysiological recovery. The present two studies investigated the undoing hypothesis and its benefits for athletes’ cognitive (Study 1; n = 60) and motor (Study 2; n = 30) performance. After a combined psychosocial-physiological stressor, participants either completed a five-minute PE induction (music; imagination exercise) or were assigned to a resting condition. Emotions, perceived stress-recovery, and physiological parameters (e.g., heart rate, heart rate variability, cortisol) were assessed. In Study 1, inhibition and cognitive flexibility were measured once. In Study 2, hand force and jump height were measured using a pre-posttest design. Due to the lack of psychological stress responses and successful PE induction, no conclusions could be drawn regarding the undoing hypothesis. Nevertheless, the present study provides valuable methodological insights into the challenges of testing the undoing hypothesis in athletes. These insights can inform the design and implementation of future studies and thereby contribute to advancing research on the undoing hypothesis in athletic populations.
Background Liver-expressed antimicrobial peptide 2 (LEAP2) is an endogenous GHSR inverse agonist that antagonizes ghrelin-mediated signaling, thereby opposing several of the physiological actions elicited by ghrelin. Evidence indicates that GHSR participates in autonomic, cardiovascular, renal, and psychogenic regulation, interacts with dopaminergic signaling and interplays with adrenergic pathways during sympathetically driven hypertension. Here, we investigated whether catecholaminergic mechanisms mediate behavioral and thermometabolic effects evoked from central GHSR inverse agonism by a LEAP2 analog. Methods Adult male Wistar rats were systemically pretreated with either the tyrosine hydroxylase inhibitor α-methyl-para-tyrosine (AMPT; 200 mg/kg) or the non-selective dopamine receptor antagonist chlorpromazine (CLP; 2 mg/kg) and then centrally pretreated with LEAP2 analog (6 nmol) or vehicle. Rats were evaluated across a range of paradigms, including anxiety- and panic-like behaviors, open-field exploration, ingestive activity, treadmill performance with VO₂ recorders and infrared thermography of caudal heat dissipation. Results Central LEAP2 analog impaired the expression of anxiety- and panic-like responses and attenuated heat-conservation mechanisms triggered by aversion. Behavioral and food ingestive effects were largely dependent on dopaminergic receptor signaling, whereas thermoregulatory responses during exercise required the entire catecholaminergic pathways inhibited by AMPT. Conclusion LEAP2 analog regulates specific behavioral and thermometabolic responses through neurobiological mechanisms involving catecholaminergic pathways and dopamine receptors, highlighting central GHSR as a potential pharmacological target for neuroendocrine defense mechanisms.
