Acquisition Of Lever Pressing Research Articles

Stress as a context: Stress causes relapse of inhibited food seeking if it has been associated with prior food seeking

Three experiments with rats explored the hypothesis that inhibited food-seeking can be reinstated by stress if stress has been part of the context of earlier food-seeking. In all experiments, rats first learned to lever press for sucrose pellets and then had the response inhibited through extinction (where responding no longer yielded sucrose pellets). In a final test, inhibited responding was tested after exposure to a stressor or not. Previous research indicates that stress during testing does not normally reinstate extinguished food-seeking, although it reliably does so when animals are responding for drugs. In Experiment 1, stress caused a reinstatement of food seeking if and only if the rats had been exposed to stressors prior to sessions of lever press training. In Experiment 2, a new stressor that had not been associated with response acquisition also caused reinstatement if other stressors had been associated with response acquisition. Experiment 3 then established that stressors must be associated with the acquisition of lever pressing, rather than extinction, in order to allow a stressor to cause relapse of extinguished food seeking. The results support the view that stress can cause relapse of inhibited food seeking if it has been part of the context of original food seeking. The effect is therefore an example of the ABA renewal effect in which inhibited responding recovers after extinction when the response is returned to its training context. Implications for understanding relapse to overeating and other “addictive” behaviors are discussed.

Running wheel exercise reduces renewal of extinguished instrumental behavior and alters medial prefrontal cortex neurons in adolescent, but not adult, rats.

Physical exercise in rodents has repeatedly been shown to trigger positive effects on brain function, including increased neurotrophic factors and improved learning and memory. However, most of this work has focused on the adult hippocampus and hippocampal-dependent behavior. Here we examined the effect of running wheel exercise in adult and adolescent male rats on ABA renewal of extinguished instrumental conditioning, in which acquisition occurs in Context A, extinction in Context B, and renewal testing occurs back in Context A. In the first experiment, rats were given unlocked (exercise) or locked (no exercise) running wheel access in their home cages beginning at postnatal Day 30 (adolescent) or postnatal Day 56 (adult). Rats underwent lever-press acquisition in Context A and extinction in Context B. ABA renewal testing took place 2 weeks after the start of running wheel exposure. Nonexercising adolescent rats showed greater ABA renewal than nonexercising adult rats and exercise reduced ABA renewal in adolescents but not adults. ABA renewal depends on medial prefrontal cortex function. In a second experiment, we compared adolescent and adult apical dendrite branch length, branch number, and spine density of medial prefrontal cortex pyramidal neurons after 2 weeks of unlocked or locked running wheel access. The results revealed a higher density of dendritic spines and a lower dendritic branch length in adolescent exercisers than adolescent nonexercisers. Adult exercisers and nonexercisers did not differ. Collectively, these experiments suggest that exercise may have particularly strong effects on adolescent medial prefrontal cortex function and structure. (PsycINFO Database Record

Motor deficits, impaired response inhibition, and blunted response to methylphenidate following neonatal exposure to decabromodiphenyl ether

Decabromodiphenyl ether (decaBDE) is an applied brominated flame retardant that is widely-used in electronic equipment. After decades of use, decaBDE and other members of its polybrominated diphenyl ether class have become globally-distributed environmental contaminants that can be measured in the atmosphere, water bodies, wildlife, food staples and human breastmilk. Although it has been banned in Europe and voluntarily withdrawn from the U.S. market, it is still used in Asian countries. Evidence from epidemiological and animal studies indicate that decaBDE exposure targets brain development and produces behavioral impairments. The current study examined an array of motor and learning behaviors in a C57BL6/J mouse model to determine the breadth of the developmental neurotoxicity produced by decaBDE. Mouse pups were given a single daily oral dose of 0 or 20mg/kg decaBDE from postnatal day 1 to 21 and were tested in adulthood. Exposed male mice had impaired forelimb grip strength, altered motor output in a circadian wheel-running procedure, increased response errors during an operant differential reinforcement of low rates (DRL) procedure and a blunted response to an acute methylphenidate challenge administered before DRL testing. With the exception of altered wheel-running output, exposed females were not affected. Neither sex had altered somatic growth, motor coordination impairments on the Rotarod, gross learning deficits during operant lever-press acquisition, or impaired food motivation. The overall pattern of effects suggests that males are more sensitive to developmental decaBDE exposure, especially when performing behaviors that require effortful motor output or when learning tasks that require sufficient response inhibition for their successful completion.

The role of pedunculopontine nucleus in choice behavior under risk

The dopaminergic projections to the basal ganglia have long been implicated in reward-guided behavior and decision-making, yet little is known about the role of the posterior pedunculopontine nucleus (pPPN), a major source of excitatory input to the mesolimbic dopamine system. Here we studied the contributions of the pPPN to decision-making under risk, using excitoxic lesions and reversible inactivation in rats. Rats could choose between two options - a small but certain reward on one lever; or a large but uncertain reward on the other lever. The overall payoff associated with each choice is the same, but the reward variance (risk) associated with the risky choice is much higher. In Experiment 1, we showed that excitotoxic lesions of the pPPN before training did not affect acquisition of lever pressing. But whereas the controls strongly preferred the safe choice, the lesioned rats did not. In Experiment 2, we found that muscimol inactivation of the pPPN also produced similar effects, but reversibly. These results show that permanent lesions or reversible inactivation of the pPPN both abolish risk aversion in decision-making.

Region‐specific impairments in striatal synaptic transmission and impaired instrumental learning in a mouse model of Angelman syndrome

Angelman syndrome (AS) is a neurodevelopmental disorder characterized by mental retardation and impaired speech. Because patients with this disorder often exhibit motor tremor and stereotypical behaviors, which are associated with basal ganglia pathology, we hypothesized that AS is accompanied by abnormal functioning of the striatum, the input nucleus of the basal ganglia. Using mutant mice with maternal deficiency of AS E6-AP ubiquitin protein ligase Ube3a (Ube3a(m-/p+) ), we assessed the effects of Ube3a deficiency on instrumental conditioning, a striatum-dependent task. We used whole-cell patch-clamp recording to measure glutamatergic transmission in the dorsomedial striatum (DMS) and dorsolateral striatum (DLS). Ube3a(m-/p+) mice were severely impaired in initial acquisition of lever pressing. Whereas the lever pressing of wild-type controls was reduced by outcome devaluation and instrumental contingency reversal, the performance of Ube3a(m-/p+) mice were more habitual, impervious to changes in outcome value and action-outcome contingency. In the DMS, but not the DLS, Ube3a(m-/p+) mice showed reduced amplitude and frequency of miniature excitatory postsynaptic currents. These results show for the first time a selective deficit in instrumental conditioning in the Ube3a deficient mouse model, and suggest a specific impairment in glutmatergic transmission in the associative corticostriatal circuit in AS.

RESPONSE ACQUISITION WITH INTERMITTENT IMMEDIATE AND DELAYED CONDITIONED REINFORCEMENT

The acquisition of lever pressing by rats was studied under intermittent immediate and delayed conditioned reinforcement. Rats were exposed to two schedules operating concomitantly. One was a random-time schedule that delivered reinforcers on average of once per min. Each such reinforcer was paired with a 1-s illumination of a cue light located above the lever. The other was a tandem random-interval (RI) t₁ - s fixed-time (FT) t₂ - s schedule that controlled the rate and the delay of the illumination of the cue-light after a given lever press. For the RI, t₁ was 7.5, 15 or 30 s. For the FT, t₂ was 0, 1, 2, 4, 8, 16 or 32 s. Three rats each were exposed to each combination of RI and FT values for 40 sessions. Response rates decreased with longer response-conditioned reinforcer (S(r)) delays under the three different overall rates of S(r). At most response-S(r) delays, absolute response rates were higher with RI 15 s than with RI 30 s but both were similar to those obtained with RI 7.5 s. The results were similar to those from previous research on response acquisition with delayed primary reinforcement. These findings suggest that a previously neutral stimulus that has been correlated with primary reinforcement can reinforce new responses even when the conditioned reinforcer is intermittent and delayed from the responses that produce it.

Effects of prenatal stress on lever-press acquisition with delayed reinforcement in male and female rats

The prenatally stressed (PS) rat shows enhanced conditioned fear and increased behavioral inhibition in response to footshock compared to control (CON) rats. It is unclear whether this facilitated learning will occur only with aversive stimulation, or if it will also be observed in the context of positive reinforcement. There are limited and inconsistent data regarding sex differences and the impact of prenatal stress on learning. The present study was designed to examine lever-press acquisition with a 10-s delay to food reinforcement in male and female PS and CON rats. Overall, twice as many PS male rats acquired the lever-press response than the PS female rats, CON male rats, and CON female rats. PS male rats also earned significantly more reinforcers and responded on the operative lever at a significantly greater rate than the other three rat groups. These findings suggest that PS rats exhibit altered learning with a task involving positive reinforcement, and this effect of PS is sex specific for male rats.

RESPONSE ACQUISITION AND FIXED‐RATIO ESCALATION BASED ON INTERRESPONSE TIMES IN RATS

The effectiveness of a fixed-ratio (FR) escalation procedure, developed by Pinkston and Branch (2004) and based on interresponse times (IRTs), was assessed during lever-press acquisition. Forty-nine experimentally naïve adult male Long Evans rats were deprived of food for 24 hr prior to an extended acquisition session. Before the start of the session, three food pellets were placed in the magazine. Otherwise, no magazine training, shaping, nor autoshaping procedure was employed. The first 20 presses each resulted in the delivery of a 45-mg food pellet. Then, the FR increased (2, 4, 8, 11, 16, 20, 25, 30) when each IRT in the ratio was less than 2 s during three consecutive ratios. Sessions lasted 13 hr or until 500 pellets were earned. On average, rats reached a terminal ratio of 11 (mean) or 16 (median) during the first session. Seven rats reached the maximum value of FR 30 and only one rat did not acquire the response. In most rats, a break-and-run pattern of responding characteristic of FR schedules began to develop in this acquisition session. Subsequently, the ratio-escalation procedure continued during daily 2-hr sessions. In these sessions, the starting ratio requirement was set at the terminal ratio reached in the previous session. Using this procedure, over half (26) of the rats reached the FR 30 requirement by the fourth session. These data demonstrate that a ratio-escalation procedure based on IRTs provides a time-efficient way of establishing ratio responding.

RESPONSE INDUCTION DURING THE ACQUISITION AND MAINTENANCE OF LEVER PRESSING WITH DELAYED REINFORCEMENT

The acquisition of lever pressing by rats and the occurrence of unreinforced presses at a location different from that of the reinforced response were studied using different delays of reinforcement. An experimental chamber containing seven identical adjoining levers was used. Only presses on the central (operative) lever produced food pellets. Groups of 3 rats were exposed to one of seven different tandem random-interval (RI) fixed-time (FT) schedules. The average RI duration was the complement of the FT duration such that their sum yielded a nominal 32-s interreinforcement interval on average. Response rate on the operative lever decreased as the FT value was lengthened. The spatial distribution of responses on the seven levers converged on the operative lever when the FT was 0 or 2 s and spread across the seven levers as the FT value was lengthened to 16 or 32 s. Presses on the seven levers were infrequent during the FT schedule. Both operative- and inoperative-lever pressing intertwined in repetitive patterns that were consistent within subjects but differed between subjects. These findings suggest that reinforcer delay determined the response-induction gradient.

The neurosteroid pregnenolone sulfate neutralized the learning impairment induced by intrahippocampal nicotine in alcohol-drinking rats

The effects of intrahippocampal administration of nicotine and the neurosteroids pregnenolone sulfate and allopregnanolone on acquiring the lever-press response and extinction in a Skinner box were examined using voluntary alcohol-drinking rats. A free-choice drinking procedure that implies early availability of the alcoholic solution (10% ethanol v/v+3% glucose w/v in distilled water) was used. Alcohol and control rats were deprived of food and assigned at random to six groups. Each group received two consecutive intrahippocampal (dorsal CA1) injections immediately after 1-h of drinking ethanol and before the free lever-press response shaping and extinction session. The groups were: saline–saline; saline–pregnenolone sulfate (5 ng, 24μM); saline–allopregnanolone (0.2μg, 1.26μM); nicotine (4.6μg, 20mM)–saline; nicotine–pregnenolone sulfate; nicotine–allopregnanolone. Blood alcohol concentrations were assessed the day before conditioning. The combination of the oral self-administration of ethanol and the intrahippocampal injection of nicotine deteriorated the ability to acquire the lever-press response. This effect was neutralized by intrahippocampal pregnenolone sulfate (negative modulator of the GABA A receptor complex), and it was not affected by intrahippocampal allopregnanolone (positive GABA receptor complex A modulator). Pregnenolone sulfate and allopregnanolone had no effects per se on lever-press acquisition, neither in alcohol-drinking rats nor in controls. Alcohol consumption facilitated operant extinction just as anxiolytics that act as positive modulators of the GABA receptor complex A receptors do, possibly reducing the anxiety or aversion related to non-reinforcement. This effect was increased by intrahippocampal nicotine.

Disturbance of rat lever-press learning by hippocampo-prefrontal disconnection

To determine whether the medial prefrontal cortex (PFC), ventral hippocampus and hippocampo-PFC pathway are involved in operant lever-press learning, we conducted lidocaine injections to these brain sites. Rats were injected immediately after lever-press acquisition in the first training, and the second 5-min test the next day. Results showed the response rate of either PFC- or ventral hippocampus-inactivated rats to be lower than that of control rats in the test the next day. Rats having lidocaine injected into the unilateral ventral hippocampus combined with contralateral medial PFC also showed lower response rate in their tests. These results suggest that hippocampo-PFC disconnection disturbs operant learning.

Dopamine and acetylcholine elevation on lever-press acquisition in rat prefrontal cortex

To determine whether the rat medial prefrontal cortex (PFC) is involved in acquiring operant learning, we observed changes in extracellular concentration of dopamine (DA) and acetylcholine (ACh) in the rat medial PFC during lever-press acquisition (acquisition group) or retrieval (retention group) using in vivo microdialysis. We found that DA or ACh elevation related to acquisition occurred. DA elevation was observed in the acquisition group only. These results indicate that the medical PFC is related to acquisition, and suggest that interaction between DA and ACh may be involved in learning acquisition.

Effects of Chlorpromazine on Rats’ Acquisition of Lever-Press Responding with Immediate and Delayed Reinforcement

The effects of chlorpromazine (0, 2, 6, and 10 mg/kg) on the acquisition of lever-press responding by rats were examined under conditions where reinforcement (water delivery) was immediate or delayed. Under the immediate reinforcement condition, water-deprived rats were exposed during 8-h sessions to a fixed-ratio 1 (FR 1) schedule of water delivery without prior autoshaping or hand shaping. Under the delayed reinforcement condition, similar rats were exposed to a tandem FR 1 fixed-time 8-s schedule of water delivery. A different squad of eight rats was exposed to each delay condition and drug dose. For all subjects, responses on one lever produced water and responses on a second lever had no programmed consequences. Regardless of whether reinforcement was immediate or delayed, chlorpromazine reduced in dose-dependent fashion the mean number of operative-lever responses emitted, which suggests that the drug interfered with learning. At all chlorpromazine doses except 10 mg/kg, substantially more operative-lever than inoperative-lever responding occurred, indicating that the operant response was acquired. Chlorpromazine at 2 and 6 mg/kg disrupted the acquisition of stimulus control by the operative lever when reinforcement was delayed, but not when it was immediate. At 10 mg/kg, most subjects did not acquire lever-pressing regardless of whether they were exposed to the immediate or delayed reinforcement procedure. Procedures similar to those used in the present study appear to provide a reasonable assay for examining how drugs affect the initial behavioral effects of immediate and delayed reinforcement, and may merit further investigation.

Body weight and response acquisition with delayed reinforcement.

The relation between body weight and responding established with unsignaled delayed reinforcement was investigated. In three experiments, naive rats were deprived to either 70%, 80%, or 90% of ad libitum weight and were then exposed to tandem variable-interval 15-s differential-reinforcement-of-other-behavior 30-s schedules. The tandem schedule defined a resetting unsignaled delay-of-reinforcement procedure. In the first experiment, speed of magazine training, acquisition of lever pressing, and final rate of lever pressing were related to body weight. In the next experiment, lever pressing was established and maintained in rats that were magazine trained at 70% of ad libitum weight but that were then exposed to the delay procedure at 90% of ad libitum weight. Responding did not change consistently either across or within subjects in subsequent conditions in which body weight was manipulated. In the final experiment, lever pressing was established and maintained with delayed reinforcement in the absence of magazine training for each of 2 rats at 70% and for 1 of 2 rats at 90% of ad libitum weight. The results further illuminate the conditions under which responding can be established in the absence of training and when such responses are reinforced only following an unsignaled delay period.

Elevation of acetylcholine in the rat prefrontal cortex related with the acquisition of lever-press

Neuronal cell bodies in the medial terminal nucleus of the accessory optic system (MTN) were labeled with WGA-HRP which was injected ipsilaterally into the occipital cortex in the rat. We suggest that the label was first transported anterogradely to the pretectal nucleus of the optic tract, then moved transneuronally from axon terminals of occipital cortical neurons to axon terminals of MTN neurons and finally transported retrogradely to reach cell bodies of MTN neurons.

2225 Elevation of acetylcholine in the rat prefrontal cortex related with the acquisition of lever-press

2225 Elevation of acetylcholine in the rat prefrontal cortex related with the acquisition of lever-press

2314 Elevation of dopamine in the rat prefrontal cortex related with the acquisition of lever-press

2314 Elevation of dopamine in the rat prefrontal cortex related with the acquisition of lever-press

Reinforcer Magnitude and Progressive Ratio Responding in the Rat: Effects of Increased Effort, Prefeeding, and Extinction

Using a between-subjects design, three experiments investigated the effects of two different magnitudes of reinforcement (one or three sucrose pellets) on lever-press acquisition and subsequent responding under a progressive-ratio 5 schedule of reinforcement. Reinforcer magnitude did not differentially affect lever-press response acquisition, but did affect the acquisition and performance of progressive-ratio responding. Rats reinforced with three sucrose pellets maintained higher break points, and responded more efficiently as indicated by shorter interresponse times and response durations. When the effort required to execute each response was increased by raising the lever above the cage floor, three-pellet rats were more resistant to the effects of lever height, and during repeated exposure to the lever height manipulation learned to adopt an efficient response style compared to rats receiving one pellet. Prefeeding the rats immediately prior to testing produced similar decreases in break points in both groups, whereas extinction resulted in greater decreases in break point in three-pellet subjects. Results from this series of experiments suggested that larger magnitudes of reinforcement increased resistance to effort, but not resistance to prefeeding or extinction, and further, that larger reinforcers enhanced the development of efficient lever-press responding.

Proactive behavioral effects of theta-driving septal stimulation on conditioned suppression and punishment in the rat.

In two experiments, a treatment phase of septal stimulation preceded the acquisition of free operant lever pressing on a random-interval 64-s reinforcement schedule. Male Sprague-Dawley rats, chronically implanted with a bilateral septal stimulating electrode and a unilateral bipolar hippocampal recording electrode, received (a) low-frequency (7.7-Hz) stimulation, which drove the hippocampal theta rhythm, or (b) random-pulse stimulation (average frequency = 7.7 Hz), which produced only nonregular waveforms in the hippocampus. Control animals were implanted but not stimulated. After 12 days of lever-press acquisition, animals were presented while lever pressing with an auditory signal associated with a particular schedule of shock delivery: In Experiment 1, shocks occurred despite the subject's response strategy; in Experiment 2, shocks were delivered only if the rat pressed the lever. In both experiments, lever pressing was suppressed by the auditory stimulus. Theta-driving but not random-pulse septal stimulation proactively increased behavioral tolerance to the effects of electric shock. These results reinforce the idea that proactive behavioral effects of septal stimulation are a consequence of the production of the hippocampal theta rhythm.

Central administration of thyrotropin-releasing hormone and histidyl-proline-diketopiperazine disrupts the acquisition of a food rewarded task by a non-aversive action

The effects of thyrotropin-releasing hormone (TRH) and its metabolites on operant behaviour have rarely been explored. In this study, the effects of intracerebroventricular (icv) administration of TRH and histidyl-proline-diketopiperazine (DKP), a metabolite of TRH, on the acquisition of a food-rewarded lever-press task were compared with saline-treated controls. TRH and DKP severely retarded the acquisition of lever pressing. The effects of systemically administered d-amphetamine were also examined in order to test whether this result was due to any stimulant properties of these peptides. These results suggest that stimulatory effects do not adequately account for impaired acquisition. The possibility that the disruption of learning was due to an aversive effect of icv administration of these peptides was tested by means of a conditioned place paradigm. Neither peptide induced an avoidance of the environment with which it had previously been paired. Several possible reasons for the peptides' adverse effect on learning are discussed, including the possibility that TRH and DKP act on attentional mechanisms.