1. Introduction {#sec1} =============== The use of drugs is associated with the onset of side effects that may significantly contribute to the morbidity and mortality of patients. Therefore, it is extremely important to monitor the use of medications in terms of both adequate drug dosage and the occurrence of adverse effects. Drug therapy can be modified in order to avoid undesirable effects or to avoid the occurrence of adverse effects. Thus, it is important to establish the mechanism of action of the studied drug and to understand the underlying pathology. Phenothiazines are an important class of drugs widely used to treat schizophrenia, mania, psychotic depression, bipolar disorder, and anxiety \[[@B1]\]. The main mechanism of action of these drugs is due to a blocking of the postsynaptic dopamine receptor \[[@B2]\]. However, there are side effects and many disadvantages that limit the clinical use of this class of drugs, mainly based on their potentiating effect on the dopamine receptor type II and its association with the development of tardive dyskinesia \[[@B3], [@B4]\]. In spite of these side effects, the use of phenothiazines is justified based on their clinical efficiency in the control of several disorders. The effects of drug abuse can be classified as positive (including euphoria, decreased anxiety, and the appearance of a tonic of wakefulness) and negative (such as anxiety, dysphoria, or irritability) \[[@B5]\]. It has been reported that the chronic administration of sub-therapeutic doses of antihistaminics and phenothiazines is associated with the suppression of anxiety and depressive behaviors \[[@B6], [@B7]\]. This drug activity is thought to be associated with an antidepressive effect and a decrease in the production of cortisol and adrenocorticotrophic hormone, as well as with an increase in the secretion of GABAergic substances \[[@B8]\]. These are the same neurotransmitters that act as regulators of the sleep-wakefulness cycle \[[@B9]\]. The occurrence of sleep disorders induced by drugs can lead to several complications, including mood disorders, irritability, and even delirium \[[@B10]\]. The use of psychotropic drugs, such as clozapine or olanzapine, has been linked with insomnia in a significant number of cases \[[@B11], [@B12]\]. In this context, the study of the interaction between sleep and drug treatment, including the role of phenothiazines, is relevant to a better understanding of the mechanisms involved in the clinical effects of these agents. Furthermore, the occurrence of acute toxicity from these drugs can cause impairment in locomotor behavior and lethality \[[@B13]--[@B15]\]. Because phenothiazines are potent sedative drugs, the evaluation of sedative effects of phenothiazine drugs is an important strategy for the safe use of these agents. Pharmaco-physiological techniques have allowed the correlation between pharmacological models and animal behavior, and these methods have been applied to the study of the acute and chronic effects of drugs. Several behavioral models have been used for the study of sedative drugs, such as pentobarbital-induced sleep \[[@B16], [@B17]\], the immobility position \[[@B18]\], swim behavior, and the open-field test \[[@B19], [@B20]\]. The objective of this study was to determine the effects of diazepam, thioridazine, and chlorpromazine, on the sleep, sleep fragmentation, and locomotor activity of mice using the open-field test. 2. Methods {#sec2} ========== 2.1. Animals {#sec2.1} ------------ Male Swiss-Webster mice (*n* = 33; weight of 20--25 g) were used in this study. They were obtained from the central animal house (UNICAMP) and housed in groups of three mice each. Mice were maintained on a 12 : 12 h light : dark cycle (lights on at 06:00 h) under controlled temperature (25 ± 2°C) and humidity (60 ± 10%) with free access to food and water. All animal experiments were performed with the authorization of the Ethics Committee of State University of Campinas, Brazil (Process Number 3015--1). 2.2. Dose and Drug Administration {#sec2.2} --------------------------------- The doses of diazepam (0.01, 0.1, 1.0, 5.0, and 10 mg/kg), thioridazine (0.05, 0.1, 0.5, 1.0, and 5.0 mg/kg), and chlorpromazine (1.0, 5.0, and 10 mg/kg) were obtained from a previous study \[[@B21]\]. The doses of diazepam, thioridazine, and chlorpromazine were administered orally. The animals were divided into eight experimental groups: group 1 (control), diazepam at 5 mg/kg; group 2, diazepam at 1 mg/kg; group 3, diazepam at 0.5 mg/kg; group 4, thioridazine at 5 mg/kg; group 5, thioridazine at 1 mg/kg; group 6, thioridazine at 0.5 mg/kg; group 7, chlorpromazine at 5 mg/kg; and group 8, chlorpromazine at 1 mg/kg. All drugs were diluted in 5 mL of distilled water and were administered orally (2 mL) 15 min before the open-field test. 2.3. Open-Field Test {#sec2.3} -------------------- The open-field test was performed between 09:00 and 11:00 h on experimental days one, four, and six (24, 48, and 72 h, resp.). The open-field consisted of a circular arena (90 cm in diameter, 50 cm in height) surrounded by walls 40 cm high. The floor of the arena was divided into 12 equal squares. The number of line crossing was manually scored for 5 min during the light phase \[[@B22]\]. The total ambulation score (crossings and rearing), time (s), and distance traveled (m) were measured. The total ambulation score was measured as an indicator of activity. The time spent in each of the four quadrants was recorded. 2.4. Statistical Analysis {#sec2.4} ------------------------- The data are reported as the mean ± S.E.M. The statistical significance of the results was determined using ANOVA. Multiple comparisons were made by the Bonferroni test. Results were considered significant at *P* \< 0.05. 3. Results {#sec3} ========== 3.1. Diazepam and Thioridazine Induce Sedation {#sec3.1} ---------------------------------------------- To investigate the effects of diazepam, thioridazine, and chlorpromazine on mice sleep, we recorded behavioral alterations in terms of the number of crossed lines. ### 3.1.1. Diazepam {#sec3.1.1} The administration of diazepam (0.5, 1, and 5 mg/kg, i.p.), as shown in [Figure 1(a)](#fig1){ref-type="fig"}, increased the number of crossed lines when compared to the control group. Mice receiving diazepam at 0.5 and 1 mg/kg spent a greater time crossing the lines than the control group (data not shown). The administration of diazepam at doses of 0.5 and 1 mg/kg decreased the amount of ambulation in the open field (data not shown). When compared to the control group, the administration of diazepam at 5 mg/kg reduced the number of crossed lines and the amount of ambulation in the open field (Figures [1(b)](#fig1){ref-type="fig"} and [1(c)](#fig1){ref-type="fig"}). However, an increased number of the ambulation of the fore paws was observed ([Figure 1(d)](#fig1){ref-type="fig"}). This result suggests that diazepam induced a sedative-like activity. ### 3.1.2. Thioridazine {#sec3.1.2} The administration of thioridazine at doses of 0.5, 1, and 5 mg/kg reduced the number of crossed lines when compared to the control group ([Figure 2(a)](#fig2){ref-type="fig"}). Although a low dose of thioridazine (0.5 mg/kg) induced sedation ([Figure 2(b)](#fig2){ref-type="fig"}), none of the doses tested (0.1, 0.5, 1.0, and 5.0 mg/kg) reduced the ambulation in the open field ([Figure 2(c)](#fig2){ref-type="fig"}). ### 3.1.3. Chlorpromazine {#sec3.1.3} The administration of chlorpromazine did not induce changes in terms of the number of crossed lines and the ambulation in the open field ([Figure 3](#fig3){ref-type="fig"}). 3.2. Diazepam and Thioridazine Decrease Locomotor Activity {#sec3.2} ---------------------------------------------------------- Because the evaluation of motor performance can be influenced by a reduction in motor activity, we examined whether the doses of diazepam and thioridazine did