Variable delay-to-signal: a fast paradigm for assessment of aspects of impulsivity in rats

Leite‐Almeida, Hugo; Melo, Antonio Carlos de Paiva; Pêgo, José M.; Bernardo, Sara; Milhazes, Nuno; Borges, Fernanda; Sousa, Nuno; Almeida, Armando; Cerqueira, João José

doi:10.3389/fnbeh.2013.00154

Cited by 24 publications

(36 citation statements)

References 33 publications

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“…We observed that KET-multiple exposure abolished the increase in the rate of PR (PR/minute) that is generally observed in the last block [3 s (f)] after the long-delay trials (6 and 12 s; Leite-Almeida et al, 2013). This effect was preserved in control animals.…”

Section: Discussionmentioning

confidence: 53%

“…To further explore the possibilities offered by VDS in the characterization of impulsivity and according to our previous studies (Leite-Almeida et al, 2013), we partitioned each delay block into 500 ms intervals (Figures 3D–K). This analysis confirmed our previous data showing a decrease of PR for the KET animals when compared with CONT animals (delay: F (3,112) = 10.44, P < 0.0001; exposure to ketamine: F (1,112) = 14.73, P = 0.0002; Figure 3C).…”

Section: Resultsmentioning

confidence: 99%

“…The VDS, which was developed in our lab, was designed and validated to evaluate impulsive behavior in a rat model (Leite-Almeida et al, 2013). In this paradigm, delay intolerance manifests as a robust increase of PR in the 3 s (f) segment when compared to the 3 s (i), i.e., after exposure to large 6 s and 12 s delays.…”

Section: Discussionmentioning

confidence: 99%

“…The VDS task (Leite-Almeida et al, 2013) was performed in a 25 cm × 25 cm × 40 cm (W × L × H) operant chamber (OC; TSE Systems, Bad Homburg, Germany). The selection wall was slightly curved and presented five squared apertures (2.5 cm 2 ), equally distributed and elevated 2 cm from the grid floor (during the VDS procedures only the middle aperture is available; see below).…”

Section: Methodsmentioning

confidence: 99%

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Exposure to Ketamine Anesthesia Affects Rat Impulsive Behavior

Melo

Leite‐Almeida

Ferreira

et al. 2016

Front. Behav. Neurosci.

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Introduction: Ketamine is a general anesthetic (GA) that activates several neurotransmitter pathways in various part of the brain. The acute effects as GA are the most well-known and sought-after: to induce loss of responsiveness and to produce immobility during invasive procedures. However, there is a concern that repeated exposure might induce behavioral changes that could outlast their acute effect. Most research in this field describes how GA affects cognition and memory. Our work is to access if general anesthesia with ketamine can disrupt the motivational behavior trait, more specifically measuring impulsive behavior.Methods: Aiming to evaluate the effects of exposure to repeat anesthetic procedures with ketamine in motivational behavior, we tested animals in a paradigm of impulsive behavior, the variable delay-to-signal (VDS). In addition, accumbal and striatal medium spiny neurons morphology was assessed.Results: Our results demonstrated that previous exposure to ketamine deep-anesthesia affects inhibitory control (impulsive behavior). Specifically, ketamine exposed animals maintain a subnormal impulsive rate in the initial periods of the delays. However, in longer delays while control animals progressively refrain their premature unrewarded actions, ketamine-exposed animals show a different profile of response with higher premature unrewarded actions in the last seconds. Animals exposed to multiple ketamine anesthesia also failed to show an increase in premature unrewarded actions between the initial and final periods of 3 s delays. These behavioral alterations are paralleled by an increase in dendritic length of medium spiny neurons of the nucleus accumbens (NAc).Conclusions: This demonstrates that ketamine anesthesia acutely affects impulsive behavior. Interestingly, it also opens up the prospect of using ketamine as an agent with the ability to modulate impulsivity trait.

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Section: Discussionmentioning

confidence: 53%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Exposure to Ketamine Anesthesia Affects Rat Impulsive Behavior

Melo

Leite‐Almeida

Ferreira

et al. 2016

Front. Behav. Neurosci.

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“…Few studies have compared alternative paradigms to the 5CSRTT, however a recent study by Leite-Almeida et al (2013) showed that impulsive responding on their novel Variable Delay-to-Signal task correlated with impulsivity during early stages of 5CSRTT training (although not when attentional load increased). It is important to note the 5CSRTT is very useful for measuring impulsive behaviour but this has not been a priority in developing the SDT.…”

Section: Discussionmentioning

confidence: 99%

Establishing a novel cognitive task in rats of relevance to schizophrenia

Turner¹

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The most debilitating symptoms for patients with neuropsychiatric disorders, such as schizophrenia, are often cognitive deficits; yet they remain largely untreated by current medications. In preclinical animal models, the techniques used to measure cognitive deficits need to be improved to enhance our ability to screen novel drug targets and gain a better understanding of the neurobiological correlates of cognitive dysfunction. Therefore, the aim of this thesis was to develop and test a new high throughput cognitive task in rodents. I have designed a novel Signal Detection Task (SDT) for this purpose.The first aim in developing the SDT was to compare alternative tasks (such as the 5-choice serial reaction time task) and address limitations including the extensive training time required and the lack of control over body position during stimulus presentation.Experiments were then selected to assess the face, construct and predictive validity of the SDT for measuring attentional deficits relevant to schizophrenia. Specifically, I determined if the effects of genetic, environmental, neurobiological and pharmacological manipulations could be detected in rats using this task. The SDT was conducted in rat operant chambers with a series of task variants to probe different components of performance, such as increasing detection difficulty and distraction. Briefly, the studies conducted compared strains (genetics), housing conditions (environment), the impact of a prefrontal cortical lesion (neurobiology) and the effects of amphetamine (pharmacology) on task performance. My findings indicate a relatively short training period was required for rats to perform the SDT with a high level of accuracy compared to other tasks; task acquisition was shown to be dependent on interactions between genetics and environment; prefrontal cortical lesions did not alter baseline performance but impaired attention during distraction and low dose amphetamine significantly improved accuracy. I demonstrated for the first time that the procognitive effects of amphetamine were dependent on baseline attentional performance. In addition, I found that individual variation in baseline performance was related to dopamine metabolism in the striatum.The research outlined in this thesis presents a novel tool for researchers exploring the cognitive phenotype of animal models relevant to neuropsychiatric disorders and for exploring the neurobiology of attention, including mechanisms of action for procognitive medication.ii Declaration by authorThis thesis is composed of my original work, and contains no material previously published or written by another person except where due reference has been made in the text. I have clearly stated the contribution by others to jointly-authored works that I have included in my thesis.

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Comparison of some behavioral effects of d- and l-methamphetamine in adult male rats

et al. 2017

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Rationale Both l- and d-methamphetamine (l- and d-MA) are more potent to release norepinephrine (NE) than dopamine, and the selectivity is greater for l-MA than d-MA. Little is known of the in vivo pharmacology of l-MA. Objective This study compared the effects of l-MA and d-MA in assays of nociception, behavioral disruption, and impulsivity. Methods Antinociceptive effects of d- and l-MA were examined in two pain assays: the warm water tail withdrawal test for acute nociception and the von Frey test in complete Freund’s adjuvant (CFA)-treated rats for chronic inflammatory pain. Food-maintained operant responding and locomotion tests were used to assess generalized behavioral disruption. The 5-choice serial reaction time test (5-CSRTT) was used to assess drug-induced effects on impulse control. A delay discounting procedure was used to determine drug-induced changes in sensitivity to reinforcer delay (impulsive choice). Results l-MA (3.2–10 mg/kg) produced dose-dependent antinociception in both pain assays, decreased the rate of food-maintained operant responding, and decreased locomotor activity at a higher dose (17.8 mg/kg). In contrast, d-MA (0.32–3.2 mg/kg) did not produce antinociception in either assay, produced biphasic effects on response rate, and increased locomotor activity. In the 5-CSRTT, d-MA but not l-MA produced significant increase in premature responses. In the delay discounting procedure, both drugs did not affect the delay function at doses that did not increase omissions. Conclusions These data suggest that d- and l-MA have different behavioral profiles. Consideration should be given to these differences in future studies when l-MA is proposed for potential therapies.

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Variable delay-to-signal: a fast paradigm for assessment of aspects of impulsivity in rats

Cited by 24 publications

References 33 publications

Exposure to Ketamine Anesthesia Affects Rat Impulsive Behavior

Exposure to Ketamine Anesthesia Affects Rat Impulsive Behavior

Establishing a novel cognitive task in rats of relevance to schizophrenia

Comparison of some behavioral effects of d- and l-methamphetamine in adult male rats

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