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Mean percent activity on conditioning days as a function of conditioning, and haloperidol dose. Percent activity was collapsed across each 60 min session. The animals had received either 0.5 mg/kg or 2.0 mg/kg of haloperidol before (P: Paired) or after (U: Unpaired) being introduced in the context-CS for 60 min. https://doi.org/10.1371/journal.pone.0200178.g001

Mean percent activity on conditioning days as a function of conditioning, and haloperidol dose. Percent activity was collapsed across each 60 min session. The animals had received either 0.5 mg/kg or 2.0 mg/kg of haloperidol before (P: Paired) or after (U: Unpaired) being introduced in the context-CS for 60 min. https://doi.org/10.1371/journal.pone.0200178.g001

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Dopamine antagonist drugs have profound effects on locomotor activity. In particular, the administration of the D2 antagonist haloperidol produces a state that is similar to catalepsy. In order to confirm whether the modulation of the dopaminergic activity produced by haloperidol can act as an unconditioned stimulus, we carried out two experiments...

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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...

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... Haloperidol induces an increase in locomotor response as a result of the blockade of presynaptic auto-receptors, which disrupts negative feedback and increases release of dopamine. 45,46 Several compounds with thermogenic and fat-oxidizing potentials also possess sympathomimetic stimulatory activity. 3,47,48 We observed higher IMP levels in the cortex of XP-treated mice, which might be related to the changes in motor behavior. ...
... More specifically, in some experiments using the so-called "bar test, " a CR of catalepsy is observed with the animals maintaining unusual postures for long periods in a drug-free trial conducted after conditioning (e.g., Amtage and Schmidt, 2003;Banasikowski and Beninger, 2012;Oliveira et al., 2016). On other occasion in which spontaneous movement over an extended period is recorded in a drug-free test after conditioning, an increase in conditioned spontaneous locomotor activity has been observed (Dias et al., 2012;De la Casa et al., 2018, 2020. These contradictory findings can be accommodated by a proposal put forward by Dias et al. (2012), who point out that, depending on the administered dose, haloperidol can lead to both an increase and decrease in locomotor activity. ...
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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.
... Therefore, pairing the contextual cues with the effect of DA agonists or antagonists allows the context to become a CS that acquires the ability to induce physiological and behavioral responses similar to those produced by the drug itself (e.g., Banasikowski and Beninger, 2010). However, there are also seemingly contradictory results in the literature, since it has recently been reported that, using haloperidol as the US, a conditioned increase in locomotor, instead of conditioned catalepsy, is observed on a drug-free test trial where the mean percentage of motor activity is recorded (De la Casa et al., 2018). One possible explanation for such a discrepancy could lie in the dose-dependent effect of haloperidol on locomotor activity, since locomotion decreases with higher doses, but increases at low doses (Dias et al., 2012). ...
... In sum, we expect to reproduce conditioned locomotor activity in a drug-free test trial after repeated pairings between the context CS and the effects induced by the administration of 0.5 mg/kg haloperidol (De la Casa et al., 2018). Additionally, we expect to observe a reduction in the expression of conditioned locomotor activity after repeated exposure to the CS context before conditioning, due to a LI effect (Lubow, 1989), and by introducing a longer ISI between haloperidol administration and context exposure (e.g., Smith et al., 1969;Yeo, 1974). ...
... In addition, half of the animals in each conditioning condition were exposed to the to-be-CS context for five consecutive days, 60-min each day, before the conditioning stage (5 Preexposure [5PE] groups), and for the other half the context was exposed only for 60-min on the day before conditioning began (1 Preexposure [1PE] groups). The introduction of a single context exposure session for the 1PE groups was programmed to identify possible differences in spontaneous motor activity between groups before the experimental treatment, and it is a standard in the procedure used in our laboratory (De la Casa et al., 2018). Although the usual control group in a LI experiment is not exposed to the to-be-CS prior to conditioning, we assume that a single exposure to the context in our experiment will not be enough to produce LI since it is ample evidence that in order to obtain such effect it is necessary a relatively high number of CS alone presentations prior to conditioning (e.g., Lubow, 1989). ...
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Previous research have shown that repeated administration of 0.5 mg/kg of haloperidol in a given context gives rise to an increase in activity when spontaneous locomotor activity is recorded in a drug-free test conducted in such context. In order to confirm whether this type of response is based on processes of a Pavlovian nature, we conducted two experiments involving two manipulations that disrupt conditioning in typical classical conditioning procedures: preexposure of the to-be-conditioned stimulus (latent inhibition), and an increase in the length of the inter-stimulus Interval. The results revealed that both manipulations were effective in reducing the conditioned increase of the locomotor response. This kind of conditioning can be explained in terms of the differential effects of low vs. high doses of haloperidol, and the temporal dynamics of conditioned response.
... That is in contradiction to our results. However, in the same study, it was proved that 8-OHDPAT can restore the locomotor stimulant effects of cocaine blocked by haloperidol and reverse the blocking effect of haloperidol on cocaine [Carey et al., 2000;De la Casa et al., 2018]. In another study, injection of 5HT1A receptor agonists such as buspirone and 8-OHDPAT increased the locomotor activity in the animal models of reduced dopamine transmission [Mignon, Wolf, 2002]. ...
... Context is commonly defined as the set of background stimuli that comprises the environment during a behavior. These same stimuli can of course also become foreground conditioned stimuli, depending on the task (De la Casa, Cárcel, Ruiz-Salas, Vicente, & Mena, 2018;Nadel & Willner, 1980). The study of context in different taste recognition memory tasks has primarily investigated spatial contexts, often defined only by visual cues (De la Casa & Díaz, 2013;Quintero et al., 2011), as well as temporal contexts, defined either as time elapsed (De la Casa et al., 2003) or the time of day (Manrique et al., 2004;Moron et al., 2002). ...
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