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Catalepsy - an immobile state in which individuals fail to change imposed postures - can be induced by haloperidol. In rats, the pattern of haloperidol-induced catalepsy is very similar to that observed in Parkinson's disease (PD). As some PD symptoms seem to depend on the patient's emotional state, and as anxiety disorders are common in PD, it is...
Citations
... The apparatus and testing procedures used for the catalepsy test have been described in detail elsewhere (Colombo et al., 2013;Barroca et al., 2019;Waku et al., 2022). Briefly, a horizontal acrylic bar (30 cm in length and 1 cm in diameter) was positioned 8 cm above the floor of a standard polypropylene box (40 × 33 × 26 cm). ...
Introduction: Dopamine has been increasingly recognized as a key neurotransmitter regulating fear/anxiety states. Nevertheless, the influence of sex and estrous cycle differences on the role of dopamine in fear responses needs further investigation. We aimed to evaluate the effects of sulpiride (a dopaminergic D2-like receptor antagonist) on contextual fear conditioning in females while exploring the influence of the estrous cycle.
Methods: First, using a contextual fear conditioning paradigm, we assessed potential differences in acquisition, expression, and extinction of the conditioned freezing response in male and female (split in proestrus/estrus and metestrus/diestrus) Wistar rats. In a second cohort, we evaluated the effects of sulpiride (20 and 40 mg/kg) on contextual conditioned fear in females during proestrus/estrus and metestrus/diestrus. Potential nonspecific effects were assessed in motor activity assays (catalepsy and open-field tests).
Results: No sex differences nor estrous cycle effects on freezing behavior were observed during the fear conditioning phases. Sulpiride reduced freezing expression in female rats. Moreover, females during the proestrus/estrus phases of the estrous cycle were more sensitive to the effects of sulpiride than females in metestrus/diestrus. Sulpiride did not cause motor impairments.
Discussion: Although no sex or estrous cycle differences were observed in basal conditioned fear expression and extinction, the estrous cycle seems to influence the effects of D2-like antagonists on contextual fear conditioning.
... Investigações histopatológicas revelaram alterações na expressão hipocampal de parvalbumina, óxido nítrico sintase neuronal (nNOS) e cFos semelhantes às encontradas na esquizofrenia humana. Foi sugerido que o Na literatura, não encontramos nenhum artigo afirmando que a dose de 0,2 mg/kg por três dias induziu síndrome extrapiramidal em ratos Wistar.Barroca et al. (2019) demonstraram que o haloperidol 0,5 e 1 mg/kg causou catalepsia significativa de 30 minutos até 75 minutos após o tratamento, sendo dose-dependente. O haloperidol 0,5 mg/kg, embora cause catalepsia da mesma forma que o haloperidol 1,0 mg/kg a partir de 45 minutos de administração, tem latência maior para atingir seu efeito de pico, exerc ...
Objective
The objective of this study was to analyze in rats models of schizophrenia, induced by the administration of ketamine, the possibility of the beneficial effects of ascorbic acid in schizophrenia, through the behavioral test.
Methods
This preliminary study was simple blind and randomized. The ketamine psychosis protocol was carried out in 24 Wistar rats, which were subsequently submitted to behavioral analysis. The first group was supplied with: water and ketamine; the second: ascorbic acid and ketamine; the third: antipsychotic, ascorbic acid and ketamine; the fourth: antipsychotic, water and ketamine. Behavioral analysis was performed using the Open Field Test, considered the standard method for assessing behavior in animal models of schizophrenia. Statistical analysis was performed by the IBM-SPSS software, using the Generalized Linear Models.
Results
Treatment in haloperidol monotherapy (Quadrant Average: 44.5 ± 15.8; CI: 13.54-75.46/Center Average: 2.67 ± 0.67; CI: 1.63-4.35) and combined with vitamin C (Quadrant Average: 38.67 ± 15.8; CI: 7.71-69.52/Center Average: 2.00 ± 0.58; CI: 1.14-3.52), demonstrated benefits in the animal model of schizophrenia induced by ketamine (Quadrant Average: 108.5 ± 15.8; CI: 77.54-139.46/Center Average: 11.33 ± 1.37; CI: 8.94- 14.37) (p < 0.001). The isolated treatment with vitamin C did not show a significant result (Quadrant Average: 62.00 ± 15.8; CI: 31.04-92.96/Mean Average: 7.00 ± 1.08; CI: 5.17-9.47).
Conclusion
The association of antipsychotic and vitamin C and only the antipsychotic demonstrated a therapeutic effect respecting to controls. Vitamin C manage separately had no benefit.
Schizophrenia; ascorbic acid; behavioral research
... In rodents, haloperidol can induce catalepsy, a state of immobility similar to Parkinson's disease (PD) bradykinesia and akinesia (De Ryck et al., 1980;Lorenc-Koci et al., 1996;Wadenberg et al., 2001;Kulkarni et al., 2009). The degree of catalepsy is commonly evaluated by the catalepsy bar test, which quantifies the time it takes for the animal to correct an externally imposed posture (Sanberg et al., 1988;Melo et al., 2010;Colombo et al., 2013;Barroca et al., 2019). Given the simplicity and ease of use of the test, haloperidol-induced catalepsy often serves as a useful animal model for the study of parkinsonism and screening of potential antiparkinsonian compounds (Waku et al., 2021). ...
... The dopaminergic modulation of adaptive responses to stressful situations is, however, less studied in the context of catalepsy. Therefore, it is of great interest to study the interplay between catalepsy and emotional states (Melo et al., 2010;Colombo et al., 2013;Melo-Thomas and Thomas, 2015;Barroca et al., 2019;Ihme et al., 2020). ...
... We have demonstrated that haloperidol reduces alarm calls emission during re-exposure to an aversive context but not to footshocks, nor during the catalepsy or open field tests, implicating heterogeneous participation of dopaminergic mechanisms contingent on the nature of the aversive stimulus (Colombo et al., 2013). Next, we verified that exposure to aversive stimuli such as open field, elevated plus-maze, and footshocks does not affect, while contextaversive conditioning seems to potentiate catalepsy (Barroca et al., 2019). Once again, the results suggest that different aversive situations, unconditioned or conditioned, seem to influence differently the cataleptic state caused by haloperidol (Barroca et al., 2019). ...
In animal models, the administration of the dopaminergic D2 antagonist haloperidol affects the nigrostriatal pathway, inducing catalepsy, a state of immobility similar to Parkinson’s disease (PD) bradykinesia and akinesia. In PD, the motor impairments are due to difficulties in selecting and executing motor actions, associated with dopamine loss in basal ganglia and cortical targets. Motor and affective limbic networks seem to be integrated via a striato-nigro-striatal network, therefore, it is not surprising that the motor impairments in PD can be influenced by the patient’s emotional state. Indeed, when exposed to aversive stimuli or life-threatening events, immobile patients are capable of performing sudden movements, a phenomenon known as paradoxical kinesia. Thus, the present study investigated the effects of unconditioned and conditioned aversive stimulation on haloperidol-induced catalepsy in rats. First, male Wistar rats received intraperitoneal administration of saline or haloperidol (1 or 2 mg/kg) and were evaluated in the catalepsy bar test to assess the cataleptic state induced by the different doses of haloperidol over time. Next, we evaluated the effects of two types of unconditioned aversive stimuli–100 lux light (1 and 20 s) or 0.6 mA footshock (1 s)–on the catalepsy. Finally, we evaluated the effects of light conditioned stimuli (Light-CS), previously paired with footshocks, on the cataleptic state. Catalepsy was observed following haloperidol 1 and 2 mg/kg administration. Exposure to footshocks, but not to light, significantly reduced step-down latency during the catalepsy test. Although unconditioned light did not affect catalepsy, paired Light-CS did reduce step-down latency. Here, we have provided evidence of face validity for the study of paradoxical kinesia. In addition to demonstrating that immediate exposure to an aversive stimulus is capable of disrupting the cataleptic state, our findings show that haloperidol-induced catalepsy seems to be differently influenced depending on the modality of aversive stimulation. Our data suggest that the selective recruitment of threat response systems may bypass the dysfunctional motor circuit leading to the activation of alternative routes to drive movement.
... Haloperidol-induced catalepsy model of neuroleptic-induced Parkinsonism was used in the present study to assess the nigrostriatal function in rodents. Haloperidol being a dopaminergic antagonist, induces cataleptic immobility in the mice (19). ...
... The time at which the animals fall was considered as cataleptic time (sec). This test was carried out on the 7th, 14th and 21st day of the study [73,74]. ...
... The gauze was ascended 20 cm overhead a solid surface, to depress the falling but not become the cause of any injury if the rat falls. The reading was taken on a stopwatch after 30 sec when the rats fell [74]. ...
... The freezing reactions which are induced either in nature, or as the result of direct brain stimulations could be related to abnormal brain state-catalepsy. The cataleptic state induced by haloperidol (modulating dopamine transmission) was shown to be sensitive to aversive stimulations [50], and this type of cataleptic reactions could be modulated by changes in glutamatergic transmission in IC [51]. This could be regarded as the indication that cataleptic muscle tone pattern has probably some common links with the brain stem defense circuits. ...
... Flight behavior and panic reaction The involvement of colliculi inferior in both states (AE and defense behavior) [2,25,[31][32][33][34]36] Behavioral freezing Cataleptic states [48][49][50][51][52] The specific neurochemicalstate in brain stem nuclei ...
The review presents data which provides evidence for the internal relationship between the stages of rodent audiogenic seizures and post-ictal catalepsy with the general pattern of animal reaction to the dangerous stimuli and/or situation. The wild run stage of audiogenic seizure fit could be regarded as an intense panic reaction, and this view found support in numerous experimental data. The phenomenon of audiogenic epilepsy probably attracted the attention of physiologists as rodents are extremely sensitive to dangerous sound stimuli. The seizure proneness in this group shares common physiological characteristics and depends on animal genotype. This concept could be the new platform for the study of epileptogenesis mechanisms.
... A particularly interesting case in the field of Pavlovian conditioning using drugs as USs is conditioning produced by pairing a neutral stimulus (typically a new experimental context) with the effects of haloperidol. This antipsychotic drug produces extrapyramidal side effects such as parkinsonism, akinesia, and acute dystonia (Lanis and Schmidt, 2001;Oliveira et al., 2016) that are related to a decrease in dopamine transmission in the striatal areas caused by the blockade of D2 receptors (Klemm, 1989;Dias et al., 2012;Barroca et al., 2019). The complexity of the conditioning process using haloperidol as the US is shown in experiments in which opposing results appear depending on the dose of the drug and type of test used. ...
Repeated pairings of a neutral context and the effects of haloperidol give rise to conditioned catalepsy when the context is subsequently presented in a drug-free test. In order to confirm whether this response is based on Pavlovian processes, we conducted two experiments involving two manipulations that affect conditioning intensity in classical conditioning procedures: time of joint exposure to the conditioned and the unconditioned stimulus, and the length of the inter-stimulus interval (ISI). The results revealed that both an increase in the length of context-drug pairings during conditioning and a reduced ISI between drug administration and context exposure increased conditioned catalepsy. These results are discussed in terms of the temporal peculiarities of those procedures that involve drugs as the unconditioned stimulus along with the role of Pavlovian conditioning in context-dependent catalepsy.
... Rats received vehicle, sulpiride (40 mg/kg) or haloperidol (0.1 or 0.25 mg/kg) 15 min before the start of the experiments. The drugs, doses and injection times were based on previous studies (de Oliveira et al. 2006Colombo et al. 2013;de Souza Caetano et al. 2013; Barroca et al. 2019). The investigator was blind to the treatment condition of each rat. ...
... The experimental protocol for the catalepsy test was based on Colombo et al. (2013) and Barroca et al. (2019). The rats were tested for catalepsy 15 and 45 min after administrations. ...
... Under our present experimental conditions, haloperidol did not seem to influence the expression or extinction of cued or contextual conditioned freezing behavior. Although based on previous studies (Colombo et al. 2013;Barroca et al. 2019), we adjusted haloperidol doses in an attempt to avoid motor impairments, we noted that haloperidol induced some degree of catalepsy, increased immobility and reduced ambulation in the open field. Therefore, motor effects influencing freezing expression during the test session cannot be discarded. ...
Dopamine seems to mediate fear conditioning through its action on D2 receptors in the mesolimbic pathway. Systemic and local injections of dopaminergic agents showed that D2 receptors are preferentially involved in the expression, rather than in the acquisition, of conditioned fear. To further examine this issue, we evaluated the effects of systemic administration of the dopamine D2-like receptor antagonists sulpiride and haloperidol on the expression and extinction of contextual and cued conditioned fear in rats. Rats were trained to a context-CS or a light-CS using footshocks as unconditioned stimuli. After 24 h, rats received injections of sulpiride or haloperidol and were exposed to the context-CS or light-CS for evaluation of freezing expression (test session). After another 24 h, rats were re-exposed to the context-CS or light-CS, to evaluate the extinction recall (retest session). Motor performance was assessed with the open-field and catalepsy tests. Sulpiride, but not haloperidol, significantly reduced the expression of contextual and cued conditioned fear without affecting extinction recall. In contrast, haloperidol, but not sulpiride, had cataleptic and motor-impairing effects. The results reinforce the importance of D2 receptors in fear conditioning and suggest that dopaminergic mechanisms mediated by D2 receptors are mainly involved in the expression rather than in the extinction of conditioned freezing.
Several useful animal models for parkinsonism have been developed so far. Haloperidol‐induced catalepsy is often used as a rodent model for the study of motor impairments observed in Parkinson’s disease and related disorders and for the screening of potential antiparkinsonian compounds. The objective of this systematic review is to identify publications that used the haloperidol‐induced catalepsy model for parkinsonism and to explore the methodological characteristics and the main questions addressed in these studies. A careful systematic search of the literature was carried out by accessing articles in three different databases, Web of Science, PubMed, and SCOPUS. The selection and inclusion of studies were performed based on the abstract and, subsequently, on full‐text analysis. Data extraction included the objective of the study, study design, and outcome of interest. 255 articles were included in the review. Publication years ranged from 1981 to 2020. Most studies used the model to explore the effects of potential treatments for parkinsonism. Although the methodological characteristics used are quite varied, most studies used Wistar rats as experimental subjects. The most frequent dose of haloperidol used was 1.0 mg/kg and the horizontal bar test was the most used to assess catalepsy. The data presented here provide a framework for an evidence‐based approach to the design of preclinical research on parkinsonism using the haloperidol‐induced catalepsy model. This model has been used routinely and successfully and is likely to continue to play a critical role in the ongoing search for the next generation of therapeutic interventions for parkinsonism.
