**1. Introduction**

Scorpions are terrestrial arthropods, which inhabit different biomes and are distributed worldwide, except in Antarctica [1].

Scorpionism is the main cause of accidents with venomous animals in Brazil having overcome snakebite since 2004 [2]. *Tityus serrulatus*, popularly known as yellow scorpion, has been described in 1922 by Lutz and Mello and is responsible for most of the serious accidents with scorpions in Brazil [3–5].

Scorpion accidents are classified according to symptoms into: mild, characterized by local signs such as edema, erythema, sweating, numbness and twitching; moderate, in which, in addition to the previous symptoms, vomiting, abdominal pain, tachypnea, tachycardia or bradycardia, hypertension, agitation, hypersalivation and priapism can also occur; and severe, in which the main symptoms are cardiovascular and pulmonary complications such as heart failure and pulmonary edema, and neurological symptoms such as encephalopathy, coma and convulsion [6].

The number of scorpion accidents has increased in the last few decades and most of the victims consist of people of reproductive age, so pregnant and lactating women are becoming possible targets [4,5]. In the state of São Paulo, between 2007 and 2019, pregnant women comprised 3% of female victims of scorpionism, with the majority during the

**Citation:** Barbosa, M.d.O.R.; de Paulo, M.E.F.d.V.; Nencioni, A.L.A. Scorpion Envenomation of Lactating Rats Decreases the Seizure Threshold in Offspring. *Toxins* **2021**, *13*, 853. https://doi.org/10.3390/ toxins13120853

Received: 15 October 2021 Accepted: 19 November 2021 Published: 30 November 2021

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second trimester of gestation [7]. However, there are no data on the number of lactating victims, and it is difficult to estimate the real proportion of victims in the perinatal period.

Experimentally, some effects of pre- or post-natal injection of Brazilian scorpion venoms in rats have been demonstrated. Prenatal injection of *T. serrulatus* venom in mothers increased the number of post-implantation losses, altered some reflex and physical parameters of the pups, and caused an increase in the weight of the placentas, liver and lungs of the pups [8–10]. Prenatal injection of *T. bahiensis* venom also increased the weight of some organs in the pups and altered physical and behavioral parameters both in childhood and in adulthood [11–13] and, when injected during lactation, it caused a delay in physical and reflex development in childhood, and reduced anxiety in adulthood [14].

Pregnancy and breastfeeding are very important for the adequate development of the pups, both from a physical and a behavioral point of view. Particularly, the quality of care offered to the newborns is important for the maturation of cerebral architecture, especially the hippocampal areas responsible for cognitive functions and stress responsiveness [15–17]. Clinical studies have demonstrated that adverse conditions such as stress early in life predispose the individual to developing several psychiatric disorders such as anxiety, depression, and epilepsy [18–20]. Experimentally, a relationship was observed between stress in perinatal period and a decrease in neurogenesis [21,22]. In addition, stress is relevant to the process of epileptogenesis, both in childhood and in adult life [23]. Hormones and neurotransmitters mediating the influence of early-life stress on excitability may create a permanent vulnerability for the development of epilepsy [20].

It is of utmost importance that the short and long term effects of scorpionism during pregnancy and lactation are well elucidated, in order to minimize the damage to the health of affected mothers and children.

Previous empirical observations conducted in our laboratory revealed a change in the pattern of care provided by mothers envenomed by scorpions during breastfeeding.

Maternal care is responsible for the proper development of the central nervous system [15,17]. Therefore, it is necessary to investigate whether the correct development of the offspring is affected by the envenomation of the mothers. We believe that the stress caused by a single dose of scorpion venom can cause changes in the behavior of the mothers, resulting directly or indirectly in altered development of the offspring.

Therefore, the present study aimed to evaluate the effect of moderate maternal envenoming on the development of the offspring's central nervous system, with particular attention paid to the susceptibility to seizures.

Pentylenetetrazole (PTZ), widely used as seizure-inducing drug, is a GABAA antagonist and suppresses the function of inhibitory synapses, leading to increased neuronal activity and consequently causes generalized seizures in animals [24]. In small doses, PTZ has been used as a model for absence seizures and in higher doses it produces convulsive seizures [25]. Here, it was used to test the convulsive threshold of the offspring of envenomed rats.

#### **2. Results**
