Effect of eugenol on lithium-pilocarpine model of epilepsy: behavioral, histological, and molecular changes

Objective(s): Epilepsy establishment gives rise to biochemical and morphological changes in the hippocampus. Oxidative stress, morphological changes, and mossy fiber sprouting (MFS) in the hippocampus underpin the epilepsy establishment. Eugenol is the main component of the essential oil extracted from cloves with the potential to modulate neuronal excitability. Therefore, we investigated the effect of eugenol on convulsive behavior, oxidative stress, and histological changes of the hippocampus in lithium- pilocarpine model of epilepsy. Materials and Methods: Male Wistar rats weighing 220–250 g were divided into 4 groups; Control, Pilocarpine, Eugenol-Pilocarpine, and Eugenol. Oxidative stress markers were assayed by a biochemical method. Nissl and Timm staining were used to show neuronal survival and MFS, respectively. Behavioral convulsions were evaluated using the modified Racine scale. Results: Eugenol decreased seizure stage and duration as well as mortality. Neuronal numbers were preserved by eugenol treatment in epileptic animals, while eugenol alone reduced the number by itself in all hippocampal sub-regions including DG, CA3, and CA1. Furthermore, eugenol alone increased MDA, GPx and SOD markers, while it increased MDA not only in combined treatment with pilocarpine but also in pilocarpine-treated animals.  In contrast to MFS enhancement in naïve animals, eugenol partially reversed the MFS enhancement induced by pilocarpine. Conclusion: Eugenol could prevent behavioral convulsions and show neuroprotective effects through increasing neuronal survival probably by decreasing MFS and increasing the GPx antioxidant marker

Intergenerational effects of maternal separation on cognitive abilities of adolescent rats

Early life adversity (ELA) is a predisposing factor for the development of behavioral and emotional disorders later in life. In humans, primates and rodents, interruption in the mother�infant relationships, and disorganized maternal care negatively influence appropriate behavioral responses and may cause cognitive deficits. Epidemiological studies suggest that ELA-induced behavioral alterations can be transmitted across generations. In this study, we investigated the cognitive abilities of male and female rats in the second filial (F2) generations whose mother, father, or both of their parents were undergoing a 180 min/day maternal separation (MS) paradigm during infancy (postnatal day (PND) 1-21). Cognitive abilities (in the open field, Morris water maze, and social interaction task) of F2 pups were tested during adolescence. Our results showed that although the mother-MS group of both sexes showed normal cognitive behavior, father-MS female pups showed more anxiety in the open field, and social interaction and spatial memory impaired in this group. These impairments were not pronounced in every detail in father-MS male pups. Moreover, rat pups that both parents experienced MS during infancy, showed normal cognitive behavior. Our data support the idea that MS-induced cognitive impairments could be transmitted across generations. Considerably, the experiences of one's parents could be inherited in the following generation in a sex-dependent manner. © 2020 International Society for Developmental Neuroscienc

Environmental enrichment and pain sensitivity; a study in maternally separated rats

Rodents are highly dependent on maternal care after birth. Maternal separation (MS) is an animal model for studying neglect and abuse. Depriving the pup of such care renders the animal with Hypothalamic�Pituitary�adrenal (HPA) dysfunction and these animals are more susceptible to anxiety and stress as well as poor cognition. These effects are due to abnormal brain development in these animals. We have tried to investigate how maternal separation can affect pain sensation and whether a non-pharmacological intervention such as enriched environment (EE) can restore an abnormal pain sensation. Animals were put into four groups MS, control (CTRL) and MS + EE and CTRL + EE groups that underwent EE after weaning until adulthood. These groups were tested for pain sensitivity with hot plate and tail flick for sensory pain and formalin for affect pain. The results showed that MS rats are more sensitive to pain in the hot plate test and formalin test, however, no significant difference was seen between groups for tail flick test. When MS rats experience EE their pain sensitivity is restored at the behavioral level. Further research is required to see how EE restores pain sensation in MS rats. © 2020 International Society for Developmental Neuroscienc

Intranasal oxytocin administration facilitates the induction of long-term potentiation and promotes cognitive performance of maternally separated rats

Maternal separation (MS) is known to induce permanent changes in the central nervous system and is associated with increased levels of anxiety and cognitive impairments. The neuropeptide oxytocin (OT) has been implicated in a broad spectrum of social and nonsocial and behaviors. Since it plays a significant role in learning and memory and enhances synaptic plasticity, we hypothesized that OT may affect MS-induced changes in synaptic plasticity and cognitive performance. Rat pups underwent MS protocol for 180 min/day from postnatal day (PND) 1�21. OT was administered intranasally (2 μg/μl, 7 days) to control and MS groups from PND 22�34. Plasma corticosterone (CORT) levels, anxiety-like behavior, sociability, learning and memory were measured in adolescent rats. In addition, extracellular evoked field excitatory postsynaptic potentials (fEPSP) were also recorded from hippocampal slices. MS induced higher plasma CORT levels and impaired social interaction, learning and memory. Moreover, MS reduced locomotor activity and increased anxiety-like behavior. Intranasal OT could overcome MS-induced deficits and promoted sociability, learning and memory of MS rats. OT also enhanced locomotor activity in the open field and decreased anxiety-like behavior. Obtained results showed that long term potentiation (LTP) was not induced in MS animals. However, OT injection overcame the MS-induced impairment in LTP generation in CA1 area of the hippocampus. © 2020 Elsevier Lt

Effect of 4-Fluoro-N-(4-sulfamoylbenzyl) Benzene Sulfonamide on cognitive deficits and hippocampal plasticity during nicotine withdrawal in rats

Withdrawal from chronic nicotine has damaging effects on a variety of learning and memory tasks. Various Sulfonamides that act as carbonic anhydrase inhibitors have documented role in modulation of various cognitive, learning, and memory processing. We investigated the effects of 4-Fluoro-N-(4-sulfamoylbenzyl) Benzene Sulfonamide (4-FBS) on nicotine withdrawal impairments in rats using Morris water maze (MWM), Novel object recognition, Passive avoidance, and open field tasks. Also, Brain-derived neurotrophic factor (BDNF) profiling and in vivo field potential recording were assessed. Rats were exposed to saline or chronic nicotine 3.8 mg/kg subcutaneously for 14 days in four divided doses, spontaneous nicotine withdrawal was induced by quitting nicotine for 72 h (hrs). Animals received 4-FBS at 20, 40, and 60 mg/kg after 72 h of withdrawal in various behavioral and electrophysiological paradigms. Nicotine withdrawal causes a deficit in learning and long-term memory in the MWM task. No significant difference was found in novel object recognition tasks among all groups while in passive avoidance task nicotine withdrawal resulted in a deficit of hippocampus-dependent fear learning. Anxiety like behavior was observed during nicotine withdrawal. Plasma BDNF level was reduced during nicotine withdrawal as compared to the saline group reflecting mild cognitive impairment, stress, and depression. Withdrawal from chronic nicotine altered hippocampal plasticity, caused suppression of long-term potentiation (LTP) in the CA1 area of the hippocampus. Our results showed that 4-FBS at 40 and 60 mg/kg significantly prevented nicotine withdrawal-induced cognitive deficits in behavioral as well as electrophysiological studies. 4-FBS at 60 mg/kg upsurge nicotine withdrawal-induced decrease in plasma BDNF. We conclude that 4-FBS at 40 and 60 mg /kg effectively prevented chronic nicotine withdrawal-induced impairment in long term potentiation and cognitive performance. © 202

What are the consequences of Methylphenidate exposure for maternally separated rats?

Methylphenidate (MPH) abuse is prevalent among youth. Drug abuse results in pain perception. We sought to investigate whether Maternal separation (MS) prone to MPH addiction. The next question was whether MPH abusers with MS differ in pain perception. We investigated the impact of MS on addiction and drug reward as well as pain perception following 5 days of MPH injection in males and females rats. Initially, rats underwent MS protocol of 3 hr daily for 21 days. Conditioned place preference (CPP) test was an attempt to investigate whether MS rats experience more reward with MPH. The protocol consisted of 10 min habituation on Day 1, conditioning on Day 2�Day 6 (5 mg per kg MPH injection in drug compartment and saline in saline compartment with 4 hr gap between injections) and 10 min test on Day 7. Furthermore, using another group, differences in pain perception were investigated after 5 days of daily MPH injection with 5 mg per kg. Sensory pain sensitivity was tested on PND 39 using tail flick and hotplate in MS and control groups with and without MPH exposure. Results indicated that female rats are equally prone to addiction in CPP. On the other hand, MS males experience a higher reward in CPP. In tail flick test, female MS rats exposed to MPH show a lower sensory pain threshold with similar MPH exposure. Experiencing MPH similarly declined hotplate pain perception in MS and controls in the females. Males, on the other hand, did not show any difference in sensory pain tests. According to results one can argue MS is detrimental. MS males experience more reward with MPH, females are equally addiction prone and MS females experience more pain in tail flick. On the other hand pain threshold can decline in hotplate test for both control and MS females that received MPH. © 2020 International Society for Developmental Neuroscienc