Opposite effects of low versus high dose haloperidol treatments on spontaneous and apomorphine induced motor behavior: Evidence that at a very low dose haloperidol acts as an indirect dopamine agonist

Dias, Flávia Regina Cruz; Matos, Liana Wermelinger de; Sampaio, Maria de Fátima dos Santos; Carey, Robert J.; Carrera, Marinete Pinheiro

doi:10.1016/j.bbr.2011.12.042

Cited by 27 publications

(30 citation statements)

References 33 publications

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“…Of note, psychosis is among the known side effects of this agent, supporting the link between increased dopamine activity and psychosis [115]. Apomorphine has also been used in pharmacological studies to evaluate the success of drugs such as haloperidol and risperidone as antipsychotics [116, 117]. Specifically, apomorphine induces emesis in dogs through its dopamine agonist properties in the gastrointestinal system and therefore has been used as a behavioral measure of dopamine function [116].…”

Section: Manipulations To Neurotransmitter Systemsmentioning

confidence: 99%

“…Specifically, apomorphine induces emesis in dogs through its dopamine agonist properties in the gastrointestinal system and therefore has been used as a behavioral measure of dopamine function [116]. This model was instrumental in screening compounds that were able to reduce emesis in dogs as potential candidates to reduce psychosis in humans [116, 117]. Although emesis in dogs has very poor construct or face validity for psychosis in humans, its use as a means to assess drugs as in vivo dopamine antagonists was instrumental in developing what remains the only effective treatment approach for psychosis, namely dopamine receptor type 2 (DR D2) antagonists.…”

Section: Manipulations To Neurotransmitter Systemsmentioning

confidence: 99%

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Animal Models of Psychosis: Current State and Future Directions

Forrest

Coto

Siegel

2014

Curr Behav Neurosci Rep

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Psychosis is an abnormal mental state characterized by disorganization, delusions and hallucinations. Animal models have become an increasingly important research tool in the effort to understand both the underlying pathophysiology and treatment of psychosis. There are multiple animal models for psychosis, with each formed by the coupling of a manipulation and a measurement. In this manuscript we do not address the diseases of which psychosis is a prominent comorbidity. Instead, we summarize the current state of affairs and future directions for animal models of psychosis. To accomplish this, our manuscript will first discuss relevant behavioral and electrophysiological measurements. We then provide an overview of the different manipulations that are combined with these measurements to produce animal models. The strengths and limitations of each model will be addressed in order to evaluate its cross-species comparability.

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Section: Manipulations To Neurotransmitter Systemsmentioning

confidence: 99%

Section: Manipulations To Neurotransmitter Systemsmentioning

confidence: 99%

Animal Models of Psychosis: Current State and Future Directions

Forrest

Coto

Siegel

2014

Curr Behav Neurosci Rep

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“…In particular, a significant increase in conditioned locomotor responses has been observed on the test trial for the paired group in comparison with the unpaired group (29–34). Less consistent are the results that have been obtained when the US employed is the dopamine antagonist haloperidol (35,36), possibly due to the fact that, depending on the dose administered, haloperidol can result in both an increase as well as a decrease in locomotor activity. More specifically, when a low dose of haloperidol (less than 0.1 mg / kg) is administered repeatedly, a progressive increase in the locomotor response is observed, which has been interpreted as the result of a sensitization process due to the selective blockade of the presynaptic autoreceptors that results in dopamine levels rising, leading to an increase in locomotor activity (36).…”

Section: Introductionmentioning

confidence: 84%

“…On the basis of previous findings, we anticipate that, with the concentrations of the drug we have used, after pairing the context with a dopaminergic antagonist (haloperidol) it will be observed a conditioned decrease in general activity (9,36–38).…”

Section: Introductionmentioning

confidence: 85%

“…), both pre and post-synaptic receptors are blocked, resulting in a reduction in locomotor behavior. This can even induce a state of catalepsy, in which the animals maintain unusual postures for prolonged periods of time (36–38). When, after repeated administration of the dopaminergic antagonist, a drug-free test is carried out in the same context in which the drug was administered, different results emerge depending on the dose of drug given during the conditioning trials.…”

Section: Introductionmentioning

confidence: 99%

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Conditioned increase of locomotor activity induced by haloperidol

Casa

Cárcel

Ruiz-Salas

et al. 2018

Preprint

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25Dopamine antagonist drugs have profound effects on locomotor activity. In 26 particular, the administration of the D2 antagonist haloperidol produces a state that is 27 similar to catalepsy. In order to confirm whether the modulation of the dopaminergic 28 activity produced by haloperidol can act as an unconditioned stimulus, we carried out 29 two experiments in which the administration of haloperidol was repeatedly paired with 30 the presence of distinctive contextual cues that served as a Conditioned Stimulus.31 Paradoxically, the results revealed a dose-dependent increase in locomotor activity 32 following conditioning with dopamine antagonist (Experiments 1) that was susceptible of 33 extinction when the conditioned stimulus was presented repeatedly by itself after 34 conditioning (Experiment 2). These data are interpreted from an associative 35 perspective, considering them as a result of a classical conditioning process. 36 37 38 Keywords: Classical Conditioning; Haloperidol; Dopamine; Locomotor Activity 3 39 Introduction 40An inherent characteristic of nature is change and, throughout the process of 41 evolution, organisms endowed with a complex nervous system have developed 42 psychological mechanisms that allow for anticipating these changes and producing 43 responses that facilitate adaptation to the environment. One such mechanism is that of 44 classical or Pavlovian conditioning, which has been proposed as a fundamental process 45 to explain how organisms learn to respond adaptively in anticipation of the occurrence 46 of environmental events (1,2). In fact, there are numerous examples that illustrate the 47 relevance of classical conditioning in the field of the study of emotional processes (3,4),48 in the acquisition of eating habits (5,6) or its usefulness for the analysis and treatment of 49 certain pathologies (7,8), among many others. 50Another area in which the adaptive relevance of Pavlovian associations has been 51 demonstrated is related to the effects of repeatedly presenting a neutral stimulus 52 accompanied by the effects of a drug. This procedure has led to seemingly 53 contradictory results, since while in some cases the Conditioned Response (CR) that 54 appears has been similar to that produced by the drug (9,10), on other occasions the 55 CR has been of an opposite nature to that induced by the drugs (11,12). Eikelboom & 56 Stewart (1982) have proposed that the origin of these differences could be related to the 57 effect of the drug on the nervous system: whilst on some occasions the Conditional 58 Stimulus (CS) is associated with an Unconditioned Response (UR) dependent on the 59 central nervous system, at other times the CS is associated with a peripheral UR that 60 will appear to compensate for the central effects of the drug. In the first case, the 61 association between the drug and the CS would lead to the appearance of a CR similar 4 62 to the one that is produced by the drug, while in the second case, the CR would be 63 opposite to that produced by the drug at the centra...

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Residual dopamine receptor desensitization following either high- or low-dose sub-chronic prior exposure to the atypical anti-psychotic drug olanzapine

et al. 2012

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The equivalent attenuation of the apomorphine sensitization produced by both olanzapine doses indicates that this effect was unrelated to the direct effects of olanzapine upon locomotion. Furthermore, the persistence of the desensitization effects well after the termination of the olanzapine treatments is indicative of a residual desensitization of the dopamine system. These findings are of importance when considering the use of atypical anti-psychotic drugs in the treatment of psychoses and other disorders in which overactivity of the dopamine system is considered a contributory factor.

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Opposite effects of low versus high dose haloperidol treatments on spontaneous and apomorphine induced motor behavior: Evidence that at a very low dose haloperidol acts as an indirect dopamine agonist

Cited by 27 publications

References 33 publications

Animal Models of Psychosis: Current State and Future Directions

Animal Models of Psychosis: Current State and Future Directions

Conditioned increase of locomotor activity induced by haloperidol

Residual dopamine receptor desensitization following either high- or low-dose sub-chronic prior exposure to the atypical anti-psychotic drug olanzapine

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