Comparison of progressive hold and progressive response schedules of reinforcement.

Progressive ratio (PR) schedules have been widely used to study motivation to work for a reinforcer. After a post-reinforcer pause, subjects engage in pressing a lever until a reinforcer is obtained. However, the discrete nature of lever presses allows alternative behaviors during inter-response time and has led to several behavioral explanations of pauses and work time. A progressive hold-down (PH) is incompatible with alternative responses and may allow a precise estimation of work time. Performance of rats trained in both PR and PH that received sucrose or intracranial self-stimulation (ICSS) as reinforcer were compared. We observed that rats mastered the PR and PH schedules. Post-reinforcer pauses (PSRP), work time and inter-reinforcer time increased as a function of the response or hold requirement. However, rats' performance suggested that the PH progression may be experienced by the rats as easier that the PR progression. Elimination of consummatory behavior with ICSS reduced post-reinforcer pause in accordance with predictions of explanatory models of fixed and variable schedules of reinforcement. In the case of PH performance, pauses showed little variation across intermediate requirements but increased rapidly on later requirements; since rats controlled their pause length and work time was close to the hold requirement, time allocation between PR and PH schedules diverged. Finally, the Mathematical Principles of Reinforcement model of Bradshaw and Killeen (Psychopharmacology 2012, 222: 549) rendered a good description of the performance in both PR and PH schedules.

Exposure to a hypercaloric diet produces long lasting changes in motivation.

Changes in motivation have been observed following induction of diet-induced obesity. However, to date, results have been contradictory, some authors reporting an increase in motivation to obtain palatable food, but others observing a decrease. Observed differences might be associated with the length of both the evaluation period and exposure to the diet. Therefore, the aim of this study was to evaluate changes in motivation during 20 weeks of exposure to a hypercaloric diet. Performance of the subjects in a progressive ratio schedule was evaluated before and during the exposure to a high-fat, high-sugar choice diet (HFHSc). A decrease in motivation was observed after 2 weeks of diet exposure, low levels of motivation remained throughout 20 weeks. A comparable decrease in motivation took longer (3 weeks) to develop using chow diet in the control group. Overall, our results suggest that, when changes in motivation are being evaluated, long periods of diet exposure made no further contribution, once motivation decreased, it remained low up to 18 weeks. Exposure to a HFHSc diet is a useful animal model of obesity, since it replicates some pathophysiological and psychological features of human obesity such as an increase in fasting glucose levels, body weight and the weight of adipose tissue.

On the Similarity Between the Reinforcing and the Discriminative Properties of Intracranial Self-Stimulation.

Rats work very hard for intracranial self-stimulation (ICSS) and tradeoff effort or time allocation for intensity and frequency parameters producing a sigmoidal function of the subjective reward magnitude of ICSS. Previous studies using electrical intracranial stimuli (ICS) as a discriminative cue focused on estimating detection thresholds or on the discrimination between intensities. To our knowledge, there is no direct comparison of the reinforcer tradeoff functions with the discriminative functions. Rats were trained to press and hold the lever for ICSS using the maximum reinforcing intensity below motor alterations or avoidance behavior. First, rats were trained to hold the lever for 1 s; after stability, they undergo trials where intensity or frequency was decreased on 0.1 log step. Thereafter, they undergo further training with a hold of 2 and later of 4 s to determine tradeoff with intensity or frequency. The same rats were trained on a discrimination task where the previously used ICSS signaled a lever where a 1 s hold response was followed by a reinforcing ICSS; on randomly alternating trials, a -0.6 log ICS signaled an alternate lever where a similar hold response led to a reinforcer. After mastering discrimination, generalization tests were carried out with varying intensity or frequency. Rats completed training with 2 and later 4 s hold response. After the completion of each task, the rats had different doses of a pimozide challenge while their intensity and hold-down requirement were varied. With regards to the rats' tradeoff response time allocation as a function of intensity or frequency, sigmoid functions were displaced to the right when long responses were required. Rats that learned the discrimination task attained a discrimination index of 90-98%. Discrimination accuracy decreased slightly with the increase of hold requirement, but generalization gradients were not displaced to the right as a function of the response requirement. Pimozide induced a dose-dependent displacement of the time-allocation gradients, but it did not affect the generalization gradients. It is concluded that rats integrate response requirements as part of the reinforcement tradeoff function, but the response cost is not integrated into the discriminative function of ICSS.

Binge eating behavior and incentive motivation with a cafeteria diet.

Binge-like eating behavior (BLE) has been characterized as an eating disorder in which subjects have an enhanced intake of food, mainly fats. However, intake of fats and carbohydrates may have differential effects on motivation. Previously it was shown that BLE produces an increase in operant responding for vegetable shortening, but others were unable to replicate the finding using sucrose as the reinforcer. Our aim was to determine if BLE behavior induced with a cafeteria-like diet (CaLD) with several options with fat content would produce an increment in performance. Male Wistar rats were trained under an exponential progressive ratio schedule of sucrose reinforcement; thereafter, the limited access model was used to induce BLE using CaLD options. Finally, subjects were tested for increments in break points (BPs) in the progressive ratio schedule. Rats with intermittent access to CaLD options showed a clear BLE with an escalation in their intake; however they showed compensatory decrements of chow intake that rendered a similar body weight gain to a continuous access group. Although we were unable to observe an increase in BPs after BLE we were able to observe a protection against the decrements of BP previously observed with sugar. Different mechanisms for processing high fat and high carbohydrate reinforcers are variables worth exploring to gain a better understanding of BLE behavior in rodent models.

Dissociation between binge eating behavior and incentive motivation.

Binge-like eating behavior (BLE) has been characterized as an eating disorder in which subjects have an enhanced intake of food, mainly fats. However, intake of fats and carbohydrates may have differential effects on motivation. Previously it was shown that BLE produces an increase in operant responding for vegetable shortening. Our aim was to determine if BLE behavior induced with a sucrose solution would produce an increment in performance for sucrose reinforcers. Male Wistar rats were trained under an exponential progressive ratio schedule of sucrose reinforcement; thereafter, the limited access model was used to induce BLE. Finally, subjects were tested for increments in break points (BPs) in the progressive ratio schedule. We were unable to observe an increase in BPs after BLE. No increments in BPs were observed when a distinctive flavor (vanilla-flavored sucrose) was correlated with BLE induction and reinforcement, or when different types of ratio progression in the operant schedules were employed. However, rats adjusted their BPs according to reinforcer concentration after BLE induction, demonstrating that valuation (cost/benefit decision) of reinforcers was intact. Extent of training, alterations of reward processing after extended exposure to sucrose, and different mechanisms for processing high fat and high carbohydrate reinforcers are variables worth exploring to gain a better understanding of BLE behavior in rodent models.

Efecto de la ingesta tipo atracón sobre la preferencia hacia diferentes concentraciones de aceite de maíz en ratas / Effects of binge eating behavior upon the preference of rats for different corn oil solutions

Resumen La ingesta tipo atracón (binge eating behavior), es un desorden alimentario que se caracteriza por un sobreconsumo de alimentos sabrosos en períodos breves sin que haya un déficit energético. Previamente se ha reportado que es posible inducir ingesta tipo atracón en ratas empleando grasa vegetal; sin embargo, se ha descrito que el consumo de grasas depende de su forma de presentación. Los sujetos que presentan atracones incremental el consumo del alimento palatable con el que fueron entrenados, pero se desconoce su preferencia cuando se ofrecen otras alternativas con diferente contenido calórico. Los objetivos del presente trabajo fueron evaluar el establecimiento de la ingesta tipo atracón empleando una solución de aceite de maíz y, si hay cambios en la preferencia de los sujetos por diferentes concentraciones de aceite de maíz después de la inducción de ingesta tipo atracón. Para ello, se realizó una línea base de la preferencia de las ratas hacia diferentes concentraciones de aceite de maíz en condiciones de acceso libre al alimento, empleando la prueba de dos botellas. Posteriormente los sujetos fueron divididos en grupo control y experimental con base en su consumo de aceite y se indujo ingesta tipo atracón en el grupo experimental; finalmente, se reevalúo de nuevo la preferencia de los sujetos en condiciones de acceso libre y, posteriormente, de privación de alimento. Los resultados obtenidos, permiten concluir que es posible inducir ingesta tipo atracón con aceite de maíz; además, la inducción de la conducta atracón aumenta la preferencia por las concentraciones altas de aceite de maíz y la privación de alimento modula dicha preferencia. Estos hallazgos implican que la regulación energética se mantiene intacta a pesar de la inducción de la conducta de atracón.

Abstract Binge eating behavior is a food intake disorder characterized by an overconsumption of palatable food without an energy deficit. It has been reported the induction of binge eating with vegetable shortening, but also it has been reported that differences may exist on consumption depending upon the fat presentation (as vegetable shortening or corn oil). In addition, there is limited information on whether binge eating may modulate preference for options that differ on their caloric content. Therefore, main objectives were to determine whether is possible to induce binge eating using corn oil as the palatable food and whether preference for different oil concentrations is modified after binge induction. First, we determined the preference of the subjects to different oil concentrations; thereafter subjects were assigned to control (no binge induction) or experimental (binge eating induction protocol) on the basis of their oil consumption. Binge induction lasted one month and then a second two-bottle preference test was carried. Results showed that corn oil may be used as a palatable substance to induce binge eating behavior; also, it was observed an increase in preference for higher oil concentrations induced by binge, but preference was also modulated by deprivation conditions, suggesting normal regulation of caloric intake despite binge induction.

Persistencia Temporal de la Conducta de Atracón en un Modelo con Ratas / Temporal Persistency of Binge Eating Behavior in Rats

Resumen La conducta de ingesta tipo atracón, se define como un consumo considerable de alimento sabroso en un periodo reducido y discreto. Los modelos experimentales con roedores que se han enfocado en este patrón de conducta asumen implícita o explícitamente que se genera un cambio permanente en el consumo de alimento sabroso, no obstante, aún no se describe la persistencia del patrón de ingesta tipo atracón, lo cual resulta de interés ya que para evaluar cualquier tratamiento es necesario conocer por cuánto tiempo los sujetos continúan presentando atracones, por lo tanto los objetivos del presente trabajo fueron: a) determinar si la conducta de ingesta tipo atracón permanece estable después de su inducción con el acceso durante 2 horas una solución de sacarosa concurrente con el acceso al alimento estándar durante 24 horas y, b) evaluar si la presencia o ausencia de alimento estándar afecta el mantenimiento de la conducta de atracón. Con este fin se dio acceso diario durante 2 horas a la solución sacarosa al 10%, mientras el acceso al alimento estándar y agua fue libre. Se observó que en 25 días los sujetos desarrollaron el patrón de ingesta tipo atracón. La conducta de atracón se mantuvo estable a lo largo de ocho semanas; ni el acceso ni la privación de alimento estándar afectaron el mantenimiento de la conducta de ingesta de atracón y el patrón de ingesta del alimento estándar se mantuvo similar al del inicio de la inducción. La estabilidad de la conducta de atracón reproduce observaciones con humanos y posibilita el estudio a largo plazo de los cambios neuronales generados durante la inducción de la conducta de atracón.

Abstract Binge eating behavior has been defined as an increased intake of palatable food during a short time period. The experimental models with rodents that had studied this eating behavior had implicitly or explicitly assumed that the induction protocol produced a permanent change in palatable eating, although there is no description of the persistence of the behavioral pattern despite this pice of information may be needed to evaluate any therapeutic strategy. Therefore, present objectives were: a) determine whether binge eating behavior persist after its induction with a 2h access to sucrose solution concurrent to free access to rat chow food for 24 h and, b) determine whether the deprivation level of chow food modulates maintenance of binge eating behavior. To this aim, rats had a 2h daily access to 10% sucrose with concurrent access to ad lib food and water. It was observed that after 25 days subjects develop binge eating behavior. It was also observed that along 8 weeks at least, binge eating behavior was stable and neither ad lib access or food deprivation modulated binge eating behavior, that remained similar to the last induction day. Stability of binge eating behavior reproduced observations with human patients and may aloud the study of long term neural changes induced after binge induction.

Attentional Mechanisms during the Performance of a Subsecond Timing Task.

There is evidence that timing processes in the suprasecond scale are modulated by attentional mechanisms; in addition, some studies have shown that attentional mechanisms also affect timing in the subsecond scale. Our aim was to study eye movements and pupil diameter during a temporal bisection task in the subsecond range. Subjects were trained to discriminate anchor intervals of 200 or 800 msec, and were then confronted with intermediate durations. Eye movements revealed that subjects used different cognitive strategies during the bisection timing task. When the stimulus to be timed appeared randomly at a central or 4 peripheral positions on a screen, some subjects choose to maintain their gaze toward the central area while other followed the peripheral placement of the stimulus; some others subjects used both strategies. The time of subjective equality did not differ between subjects who employed different attentional mechanisms. However, differences emerged in the timing variance and attentional indexes (time taken to initial fixation, latency to respond, pupil dilatation and duration and number of fixations to stimulus areas). Timing in the subsecond range seems invariant despite the use of different attentional strategies. Future research should determine whether the selection of attentional mechanisms is related to particular timing tasks or instructions or whether it represents idiosyncratic cognitive "styles".

La administración del antagonista GABA A bicuculina previene los efectos de la administración del agonista 5-HT 1A 8-OH-DPAT en las propiedades discriminativas de la anfetamina / Administration of GABA A receptor antagonist bicuculline prevents the effects of administration of 5-HT 1A receptor agonist on the discriminative properties of amphetamine

Resumen En esta investigación se evaluaron los efectos de la administración sistémica del antagonista GABAA bicuculina sobre los efectos del agonista 5-HT1A 8-OH-DPAT en las propiedades discriminativas de la anfetamina (ANF) utilizando el condicionamiento de aversión a los sabores. Los resultados mostraron que ni el 8-OH-DPAT, ni la bicuculina, sustituyeron la señal discriminativa de la ANF. Sin embargo, la administración del 8-OH-DPAT disminuyó la señal discriminativa de la ANF, y la administración de la bicuculina, previa a la administración del 8-OH-DPAT más una dosis de ANF, previno el efecto del 8-OH-DPAT sobre la señal discriminativa de la ANF. Estos datos apoyan la hipótesis de que las conductas relacionadas con la adicción a las drogas, como la ANF, involucran diferentes sistemas de neurotransmisión como la DA, la 5-HT y el GABA.

Abstract In this research, the effects of systemic administration of the GABAA receptor antagonist bicuculline on the effects of 5-HT1A receptor agonist 8-OH-DPAT on the discriminative properties of the AMPH using the conditioned taste aversion procedure were evaluated. The results showed that neither 8-OH-DPAT nor bicuculline administration did not substitute for AMPH. However, the 8-OH-DPAT administration decreased the discriminative signal of AMPH and the bicuculline administration, prior to the 8-OH-DPAT administration plus a dose of AMPH prevented the effect of the 8-OH-DPAT on discriminative signal of AMPH. These data support the hypothesis that addiction-related behaviors of drugs such as AMPH involve several neurotransmitter systems such as DA, 5-HT and GABA.

Dorsolateral frontal cortex and peripheral muscarinic receptors participation in the discriminative stimulus properties of scopolamine in rats.

Organisms are capable of making decisions based on their ability to discriminate between different stimuli. This principle is fundamental for the adaptation of organisms to their environment, by emitting appropriate behaviors based on a previously acquired discriminative process. The present study analyzed the participation of the peripheral nervous system, the M1 muscarinic receptor subtype, as well as the contribution of the dorsolateral frontal cortex to discrimination process using scopolamine as discriminative stimulus. Male Wistar rats were trained to discriminate between scopolamine (1.0 mg/kg) and saline injections (i.p.) using a two-lever operant procedure. Once discrimination was acquired, generalization curves for scopolamine, methylscopolamine, pirenzepine, dorsolateral frontal cortex lesion and control conditions were obtained. Results showed that rats were able to discriminate and generalize its responses to different doses of scopolamine but not for methylscopolamine or pirenzepine, thus the data suggest that discriminative properties of scopolamine are processed in CNS and that the M1 receptor does not participate in this process. Dorsolateral frontal cortex lesion did not produce any statistically significant difference in the generalization curve, which suggests that a system different from the dorsolateral prefrontal cortex may be responsible for the control of stimulus produced by scopolamine.

The GABA-B antagonist 2-hydroxysaclofen reverses the effects of baclofen on the discriminative stimulus effects of D-amphetamine in the conditioned taste aversion procedure.

Some of the behavioral effects of d-amphetamine (d-AMPH) are mediated by an increase in dopamine neurotransmission in the nucleus accumbens. However, there is evidence that gamma-amino-butyric-acid-B (GABA-B) receptors are involved in some behavioral effects of D-AMPH and cocaine. Here, we examined the effects of baclofen on the discriminative stimulus properties of D-AMPH, using conditioned taste aversion (CTA) as the drug discrimination procedure. Male Wistar rats were deprived of water and trained in the CTA procedure. They received D-AMPH (1 mg/kg, i.p.) before gaining access to saccharin, which was followed by an injection of LiCl. On alternate days, the subjects received saline before and after the access to saccharin. After the rats learned the D-AMPH-saline discrimination, the standard dose of D-AMPH was replaced by different doses of D-AMPH, baclofen (a GABA-B receptor agonist), 2-hydroxysaclofen (a GABA-B receptor antagonist), a combination of baclofen+D-AMPH, or a combination of 2-hydroxysaclofen+baclofen+D-AMPH. Baclofen did not substitute for D-AMPH, but, when combined with D-AMPH, it produced a small but significant decrease in the discriminative stimulus effects of D-AMPH. This effect was reversed by administration of 2-hydroxysaclofen. These data suggest that GABA-B receptors play a regulatory role in the discriminative stimulus effects of D-AMPH.

Modulatory role of 5-HT1B receptors in the discriminative signal of amphetamine in the conditioned taste aversion paradigm.

Drugs of abuse, such as amphetamine (AMPH), share the ability to activate the mesolimbic dopamine (DA) system. The behavioral effects of AMPH are largely mediated by increased DA neurotransmission in the nucleus accumbens. However, there is evidence that serotonin (5-hydroxytryptamine - 5-HT) systems may regulate forebrain DA function. We examined the role of 5-HT1B receptors on the discriminative stimulus properties of AMPH using conditioned taste aversion (CTA) as the drug discrimination procedure. Male Wistar rats were deprived of water and trained in the CTA procedure. They received the administration of AMPH (1.0 mg/kg) before a 10 min period of access to saccharin solution and followed by an injection of LiCl; on alternate days, rats received saline before and after the access to saccharin solution. In generalization and combination tests, the training dose of AMPH was substituted by 5-HT1B receptor ligands RU24969 (5-HT1B agonist: 0.1, 0.3 and 1.0 mg/kg), CP94253 (5-HT1B agonist: 1.0, 3.0 and 5.6 mg/kg) and GR127935 (5-HT1B antagonist: 0.3, 1.0 and 3.0 mg/kg) or a combination of RU24969 (0.1, 0.3 and 1.0 mg/kg), CP94253 (1.0, 3.0 and 5.6 mg/kg) or GR127935 (0.3, 1.0 and 3.0 mg/kg) with AMPH (0.3 mg/kg) or GR127935 (0.3, 1.0 and 3.0 mg/kg) and CP94253 (5.6 mg/kg) with AMPH (0.3 mg/kg). The results showed that 5-HT1B agonists RU24969 and CP94253 produced partial generalization of 48% and 60%, respectively, and the 5-HT1B antagonist GR127935 neither substituted for AMPH nor affected the discriminative cue of AMPH; however, when RU24969 or CP94253 were administrated in combination with AMPH, they increased the discriminative cue of AMPH. This effect was reversed by the administration of 5-HT1B antagonist GR127935. These data suggest that 5-HT1B receptors play a modulatory role in the discriminative cue of AMPH.