Differential involvement of prefrontal cortex,striatum, and hippocampus in DRL performance in mice

Behavioral effects of neurotoxic lesions of the hippocampus, medial prefrontal (prelimbic, infralimbic and anterior cingulate) cortex or dorsal striatum were assessed using a DRL-10s schedule in mice. Post-operative acquisition data indicate that mice with hippocampal, but not prefrontal or striatal lesions received fewer reinforcements during daily 30-min sessions, and were less efficient in the timing of their responses. Additional analysis of inter-response-time (IRT) distributions revealed that the responses of hippocampal-lesioned mice exhibited undistinguishable responses for short IRTs (up to 9s). In addition, prefrontal-lesioned mice demonstrated a degradation of performance with further testing, and a flattened IRT distribution at late test phase, while striatal-lesioned mice behaved similarly to sham-lesioned mice. These results are interpreted in terms of known functions of the hippocampus in behavioral inhibition, and of the prefrontal cortex in executive control/decision making (and time production).     

Operant hoarding: a new paradigm for the study of self-control.

In the first of four experiments, rats were exposed to a modified multiple continuous reinforcement-extinction schedule during 15-min daily sessions. In one condition (saves condition) with the cuelight on, a single lever press produced a food pellet, briefly extinguished the cuelight, and started a clock. Saves (additional lever presses with interresponse times less than 1 s) produced an additional food pellet, briefly extinguished the cuelight, and restarted the interresponse time clock. The cuelight was extinguished 1 s after the last lever press and remained off during a 10-s period of extinction, during which no food pellets were delivered. In the other condition (savings account condition), the contingencies were the same except that the cuelight was extinguished and was not reilluminated after the initial lever press, and the delivery of all food pellets in the reinforcement component was delayed until the onset of extinction. In both conditions, rats made saves, but mean saves (total saves divided by the number of reinforcement components) were slightly reduced in the savings account condition. In Experiment 2, using six equally spaced 15-min sessions per day on alternate days, saves were either followed immediately with food and brief cuelight offset (saves condition) or were not reinforced at all. Mean saves were much greater when saves were reinforced. In Experiment 3, during 5-min daily sessions, saves earned a single pellet (savings account condition) or a number of pellets equal to the ordinal number of the lever press (interest condition). Rats made fewer mean saves, with little change in the food rate, when saves earned interest. In Experiment 4, the rats earned all their food in the operant situation during 24 daily 5-min sessions, these separated by 55-min intersession intervals during which no food was available; otherwise, the conditions were the same as in Experiment 3. In Experiment 4, the shift to interest for saves led to an increase in mean daily mean saves (total daily mean saves divided by the number of daily sessions) as well as to an increase in the number of food pellets delivered in each session. The results are discussed in terms of self-control and behavioral economics.     

Effects of post-session wheel running on within-session changes in operant responding

This study tested the effects of post-session wheel running on within-session changes in operant responding. Lever-pressing by six rats was reinforced by a food pellet under a continuous reinforcement (CRF) schedule in 30-min sessions. Two different flavored food pellets were used as reinforcers. In the wheel conditions, 30-min operant-sessions with one of the flavored pellets were followed by 30-min free-wheel running sessions. Meanwhile, in the home conditions, rats’ operant responding was reinforced by the other flavored pellets during 30-min operant-sessions, and the rats were then returned to their homecages. All rats were exposed to 4 wheel and 4 homecage sessions. Operant responding was lowered during the wheel conditions. However, post-session running did not alter the within-session pattern of operant responding. These effects were practically identical to the effects of drug-induced taste-aversion learning on within-session changes in operant responding, suggesting similar mechanisms in both taste-aversion preparations.     

Stock optimizing: maximizing reinforcers per session on a variable-interval schedule.

In Experiment 1, 2 monkeys earned their daily food ration by pressing a key that delivered food according to a variable-interval 3-min schedule. In Phases 1 and 4, sessions ended after 3 hr. In Phases 2 and 3, sessions ended after a fixed number of responses that reduced food intake and body weights from levels during Phases 1 and 4. Monkeys responded at higher rates and emitted more responses per food delivery when the food earned in a session was reduced. In Experiment 2, monkeys earned their daily food ration by depositing tokens into the response panel. Deposits delivered food according to a variable-interval 3-min schedule. When the token supply was unlimited (Phases 1, 3, and 5), sessions ended after 3 hr. In Phases 2 and 4, sessions ended after 150 tokens were deposited, resulting in a decrease in food intake and body weight. Both monkeys responded at lower rates and emitted fewer responses per food delivery when the food earned in a session was reduced. Experiment 1's results are consistent with a strength account, according to which the phases that reduced body weights increased food's value and therefore increased subjects' response rates. The results of Experiment 2 are consistent with an optimizing strategy, because lowering response rates when food is restricted defends body weight on variable-interval schedules. These contrasting results may be attributed to the discriminability of the contingency between response number and the end of a session being greater in Experiment 2 than in Experiment 1. In consequence, subjects lowered their response rates in order to increase the number of reinforcers per session (stock optimizing).     

The Effect of Stress on Spontaneous Nest Leaving Behavior in the Mouse: An Improved Model of Stress-Induced Behavioral Pathology

The present experiments were conducted to develop a more sensitive and reliable model of stress-induced behavioral pathology in the mouse. Male mice were housed singly in nest cages connected to either a circular tunnel, a recreational cage or a large box with food foraging apparatus. Spontaneous nocturnal out of nest activity or food foraging behavior in these environments was continuously monitored for a two week period during which time the effects of stress were examined. It was found that both repeated restraint and aggression stress markedly and persistently reduced out of nest nocturnal activity or food foraging behavior in all 3 environments but did not alter activity in a novel open field or plus maze or food or saccharin intake in the nest cage. In a preliminary experiment the reduction in out of nest activity by stress was attenuated by prior chronic treatment with the antidepressant, desmethylimipramine. Plasma corticosterone was elevated immediately after aggression stress but reduced 5 hr after chronic aggression stress. The reduction in activity did not appear the result of increased anxiety as measured by spontaneous risk assessment behavior in the nest. It is concluded that the decrease in out of nest activity after stress in the present studies models a withdrawn behavioral state and may be due to either or both a decrease in appetitive motivation to leave the nest or an increased aversion to the external environment which does not apparently involve anxiety.     

Blood pressure hyperreactivity in non-human primates during dietary sodium combined with behavioral stress

The potential for behavioral stress alone or combined with dietary salt to augment pressor reactivity to the onset of daily experimental sessions was examined in normotensive, intact baboons over the course of four months. During twice daily experimental sessions, adult male baboons experienced food/shock conflict such that lever pulling not only served to earn food, but was also occasionally punished with cued mild electric shock. Blood pressure and heart rate were measured during a baseline period of fixed-ratio food reinforcement (3 weeks), during conflict stress (2 weeks), and after dietary salt was added to the daily conflict protocol (CONFLICT + SODIUM, 3 weeks). Reactivity, i.e., acute changes in blood pressure and heart rate to the daily experimental sessions, was not evident during food reinforcement sessions nor during the CONFLICT stress alone condition. The addition of a high salt diet virtually doubled blood pressure increases and heart rate decreases to the onset of experimental sessions. Average reactivities during CONFLICT + SODIUM periods were 11.2/7.9% delta for SBP/DBP (systolic/diastolic blood pressure, mmHg), and -5.65% delta for HR (heart rate, BPM). Neither atenolol nor hydrochlorothiazide diuretic significantly altered cardiovascular reactivity during CONFLICT + SODIUM in comparison to a preceding non-drug CONFLICT + SODIUM period. When atenolol and diuretic effects were directly compared, atenolol mildly augmented, while diuretic mildly decreased DBP but not SBP reactivity during CONFLICT + SODIUM. Reactivity was eliminated after salt loading and behavioral sessions were terminated. These findings provide evidence that enhanced salt ingestion may synergistically act with behavioral stress to produce pressor hyperresponsiveness to otherwise benign environmental events.     

Lesions in the Central Nucleus of the Amygdala: Discriminative Avoidance Learning, Discriminative Approach Learning, and Cingulothalamic Training-Induced Neuronal Activity

The amygdala is critically involved in discriminative avoidance learning. Large lesions of the amygdala block discriminative avoidance learning and abolish cingulothalamic training-induced neuronal activity. These results indicated that amygdalar processing is critical for cingulothalamic plasticity. The larger lesions did not allow differentiation of the specific functioning of various amygdalar nuclei. Anatomical analysis showed that damage in the central (CE) nucleus of the amygdala was correlated with the severity of the behavioral deficit. The present study was carried out to determine whether smaller lesions, centered in the CE nucleus, would impair discriminative avoidance learning and block cingulothalamic plasticity. In addition, the possible role of the CE nucleus in appetitively motivated discriminative approach learning was examined for the first time. New Zealand White rabbits with CE nuclear lesions were first trained in the discriminative approach task. After attaining asymptotic performance, discriminative avoidance training sessions were alternated with continuing approach training sessions, one session each day. The rabbits with lesions were severely impaired in avoidance learning but showed no impairment of approach learning. Surprisingly, the attenuating effects of the lesions on cingulothalamic training-induced neuronal activity were more prevalent during approach learning than during avoidance learning. These results indicated that avoidance learning can be impaired by lesions centered in the CE nucleus that leave cingulothalamic plasticity largely intact and that the CE nucleus is involved in extra-cingulothalamic learning processes.     

Development of key-pecking, pause, and ambulation during extended exposure to a fixed-interval schedule of reinforcement

Six pigeons key-pecked under a fixed-interval (FI) 3-min schedule of food presentation. Each pigeon was studied for 200 daily sessions with 15 intervals per session (3,000 total food presentations). Analyses included the examination of latency to first peck (pause), mean rate of key pecking, and ambulation. Characterizations of stable performance were assessed across measures of behavior and evaluated using commonly employed stability criteria. Stability of response rate and pause was identified better by assessments that evaluated variability and trend, rather than just variability. Between-subject differences in rate of acquisition and terminal values of steady-state performance of pause were observed, and stable pause durations took longer to develop than did stable key-pecking rates. Relative variability in response rate and pause duration decreased as the means increased. A temporally organized pattern of key-pecking (the so-called FI scallop) developed within 50 sessions of exposure to the schedule. Overall ambulation decreased during the early sessions of exposure and further analyses showed greater rates of ambulation during the pause than after it for 4 of the 6 pigeons. Performance under the FI 3-min schedule developed relatively slowly, and key-pecking, pause, and ambulation developed at different rates.     

A developmental study of schedule-induced polydipsia in the rat

Rats 30, 60, 90, and 120 days of age were fed 105 45-mg food pellets on a noncontingent VT 70-sec schedule during 14 daily 2-hr sessions. Every animal became polydipsic on this schedule when compared with a schedule in which 105 pellets were presented at the beginning of the session. Mean polydipsic ratios (schedule intake/control intake) ranged from 2.9–5.4. Water intakes (milliliters per 100g body weight) did not differ during the last five sessions as a function of age. The results are discussed with respect to the generality of the class of adjunctive behaviors.     

Anticipation of future food: suppression and facilitation of saccharin intake depending on the delay and type of future food

A series of studies examined the (Sprague-Dawley) rat's tendency to suppress intake of .15% saccharin when it was followed by a second food after 4-, 16-, or 32-min delays. The second foods examined were 32% sucrose, 64% sucrose, lab chow, a Nutrasweet solution, skim milk, and chocolate milk. Saccharin intake was influenced by both the delay and the specific food available. Subsequent analysis showed that saccharin intake before the 4-min delay was an inverse function of the caloric value of the second food. However, saccharin intake before the 16-min delay was better predicted as an inverse function of the hedonic value of the second food. The results suggest that the caloric and hedonic values of a food may influence food selection across different time courses, and that the effective time horizon for the sequential comparison of foods depends on the specific foods that are compared.     

Telemetry provides new insights into entrainment of activity wheel circadian rhythms and the role of body temperature in the development of ulcers in the activity-stress paradigm

Two methods of monitoring the circadian rhythm of activity in rodents: (1) an activity wheel cage, which detects the number of wheel revolutions, and (2) an internal radio transmitter, which records gross motor activity (GMA) of the animal, were compared in both normal circadian cycles and during the development of activity-stress ulcers. Rats were implanted with a biotelemetry transmitter that detected GMA and body temperature (BT) and placed in activity wheel cages. A 12 hour/12 hour light/dark cycle was maintained throughout the experiment. Subjects were subdivided into two groups: (1) unlimited access to activity wheel (AW) cages and (2) locked activity wheel (LW) cages. Following an ad-libitum habituation period, animals were allowed food access for 1 hour/day during the light. In the habituation period, the animals showed higher GMA and BT during the dark phase when housed in AW cages than in LW cages. Both GMA and number of wheel revolutions increased dramatically after the onset of food restriction for the AW animals. There was a deleterious drop in BT in AW animals as the food-restricted period continued and a significant correlation existed between severity of ulcerations and BT. The findings of this experiment demonstrate that the activity wheel imposes an alternation of the circadian cycle, which, in turn, influences rhythmicity through reentrainment. Additionally, in the activity-stress paradigm, a significant drop in BT correlates with severity of ulcerations. A disrupted circadian cycle, involving hypothermia, is proposed as the mechanism underlying the demise of animals in the activity-stress paradigm.     

Telemetry Provides New Insights into Entrainment of Activity Wheel Circadian Rhythms and the Role of Body Temperature in the Development of Ulcers in the Activity-Stress Paradigm

Two methods of monitoring the circadian rhythm of activity in rodents: (1) an activity wheel cage, which detects the number of wheel revolutions, and (2) an internal radio transmitter, which records gross motor activity (GMA) of the animal, were compared in both normal circadian cycles and during the development of activity-stress ulcers. Rats were implanted with a biotelemetry transmitter that detected GMA and body temperature (BT) and placed in activity wheel cages. A 12 hour/12 hour light/dark cycle was maintained throughout the experiment. Subjects were subdivided into two groups: (1) unlimited access to activity wheel (AW) cages and (2) locked activity wheel (LW) cages. Following an ad-libitum habituation period, animals were allowed food access for 1 hour/day during the light. In the habituation period, the animals showed higher GMA and BT during the dark phase when housed in AW cages than in LW cages. Both GMA and number of wheel revolutions increased dramatically after the onset of food restriction for the AW animals. There was a deleterious drop in BT in AW animals as the food-restricted period continued and a significant correlation existed between severity of ulcerations and BT. The findings of this experiment demonstrate that the activity wheel imposes an alternation of the circadian cycle, which, in turn, influences rhythmicity through reentrainment. Additionally, in the activity-stress paradigm, a significant drop in BT correlates with severity of ulcerations. A disrupted circadian cycle, involving hypothermia, is proposed as the mechanism underlying the demise of animals in the activity-stress paradigm.     

Handling from weaning to adulthood does not prevent hyperdefensiveness induced by septal, medial accumbens, or medial hypothalamic lesions

Weanling male hooded rats were handled or not handled for 10 min each day, 5 days/week, for 6 weeks. At the end of this time all animals received one of the following: a septal lesion, a medial accumbens lesion, a medial hypothalamic lesion, or a sham lesion. The animals were tested for defensiveness toward the experimenter on Days 3, 7, and 14 postoperatively. All behavioral testing was done blind. Each of the three lesions increased defensiveness toward the experimenter. However, with each lesion, there was no difference in the defensiveness scores of preoperatively handled and nonhandled animals at any of the postoperative test sessions while those of animals with medial hypothalamic lesions did not. These results are consistent with observations that hyperdefensiveness occurs in human subjects following tumors in each of these brain areas in spite of their familiarity with the situation in which they are observed. They contrast with observations that mouse killing induced by septal lesions is readily prevented by preoperative exposure to a mouse.     

Time of supplemental feeding alters the effects of cocaine on lever pressing of rats

The present experiment assessed the effects of cocaine on the lever pressing of 4 rats maintained during 15-min sessions by a fixed-ratio 50 schedule of food reinforcement. Across phases, supplemental food was provided either immediately or 2 hr after sessions. Two rats began the experiment in the delayed-feeding condition, and 2 began the experiment in the immediate-feeding condition. Rates of lever pressing of 2 rats sometimes decreased to low levels near the ends of sessions when supplemental feeding was provided immediately, but were consistently high throughout sessions when supplemental feeding was delayed. Cocaine (1.0 to 17.0 or 30.0 mg/kg) was administered intraperitoneally 15 min prior to test sessions. In most cases, cocaine suppressed response rates at lower doses under immediate-feeding conditions. Decreases in overall response rates were correlated with dosedependent increases in the time rats spent not responding. It is suggested that delaying the time of postsession feeding increased response strength, as indicated by greater resistance to the rate-suppressive effects of cocaine.     

Session duration and the VI response function: Within-session prospective and retrospective effects

Two experiments examined the effects of session duration on responding during simple variable-interval schedules. In Experiment 1, rats were exposed to a series of simple variable-interval schedules differing in both session duration (10 min or 30 min) and scheduled reinforcement rate (7.5 s, 15 s, 30 s, and 480 s). The functions relating response rate to reinforcement rate were predominantly monotonic for the short (10-min) sessions but were predominantly bitonic for the long (30-min) sessions, when data from the entire session were considered. Examination of responding within sessions suggested that differences in the whole-session data were produced by a combination of prospective processes (i.e., processes based on events scheduled to occur later in the session) and retrospective processes (i.e., processes based on events that had already occurred in the session). In Experiment 2, rats were exposed to a modified discrimination procedure in which pellet flavor (standard or banana) predicted session duration (10 min or 30 min). All rats came to respond faster during the short (10-min) sessions than during the first 10 min of the long sessions. As in Experiment 1, the results seemed to reflect the simultaneous operation of both prospective and retrospective processes. The results shed light on the recent controversy over the form of the variable-interval response function by identifying one variable (session duration) and two types of processes (prospective and retrospective) that influence responding on these schedules.     

Slower eating rate reduces the food intake of men, but not women: implications for behavioral weight control

This study tested a central tenet of behavioral weight control: does slower eating rate reduce food intake and positively affect appetite ratings. This study used direct behavioral observation of participants' (n=48; 25BMI35) eating behavior using Universal Eating Monitors. Food intake and ratings of "desire to eat" (collected each minute during meals) were represented as a function of time. Based on an acclimation meal, participants' eating rate was modified by instructing them to eat a bite of food when prompted by a computer, which generated three types of meals: (1) baseline (eating rate was the same as the acclimation meal), (2) reduced-rate (eating rate was reduced by 50%), and (3) combined-rate (eating rate at the beginning of the meal was identical to that of the acclimation meal, subsequently eating rate was reduced by 50%). All meals were ad libitum. Slower eating rate during the reduced-rate and combined-rate meals resulted in less food intake compared to the baseline meal for men, but not women. Ratings of desire to eat, normalized for the amount of food consumed, were lower during the combined-rate meal for men and women. Thus, this basic premise of behavioral weight control was supported for men, but not for women.     

Home cage testing of delay discounting in rats

Testing rodents in their home cages has become increasingly popular. Since human intervention, handling, and transport are minimized, behavior can be recorded undisturbed and continuously. Currently existing home cage systems are too complex if only relatively simple operant-learning tests are to be carried out in rats. For that purpose, a new low-cost computer-controlled operant panel was designed, which can be placed inside the home cage. A pilot study was carried out, using an intolerance-to-delay protocol, classically developed for testing behavioral impulsivity. Male adult rats were tested in their home cages, containing the operant panel provided with nosepoking holes. Nose poking in one hole resulted in the immediate delivery of one food pellet (small-soon, SS), whereas nose poking in the other hole delivered five food pellets after a delay (large-late), which was increased progressively each day (0–150 sec). The two daily sessions, spaced 8 h apart, lasted 1 h each, and the time-out after food delivery was 90 sec. A clear-cut shift toward preference for SS, which is considered a classical index of cognitive impulsivity, was shown at the longest delay. It is noteworthy that rats shifted when the delay interval was longer than the mean intertrial interval—that is, when they experienced more than one delay-equivalent odds against discounting (see Adriani & Laviola, 2006). The shortened training (2 days) and testing (5 days) phases, as allowed by prolonged and multiple daily sessions, can be advantageous in testing rodents during selected short phases of development. Current research is focusing on further validation of this and similar protocols.     

Behavioral contrast and the automaintained key peck

In two experiments behavioral contrast was demonstrated during discrimination training in a positive automaintenance procedure. During the baseline condition in each experiment, a key was transilluminated for eight seconds by one of two colors (CS) following a variable intertrial interval signaled by a dark key. Keylight transillumination terminated with a response-independent food presentation. In the first experiment, food was eliminated during one CS for up to fifty sessions. After reinstatement of food following each CS, the discrimination was reversed. Six of the eight subjects showed positive behavioral contrast, i.e., response rates increased during the CS associated with food as they decreased during the CS associated with no food. The effect was replicated in Experiment II, but it did not occur when both the food and its associated CS were eliminated. These results were comparable to those obtained with operant discrimination training procedures (behavioral contrast) and with Pavlovian discrimination training. The results suggest that additivity theories of behavioral contrast may be insufficient to account for these data.     

The effect of acceleration on food-reinforced DRL and FR

Performance on DRL 10 sec and FR 5 was studied after exposure to acceleration. After four rats, two on each of the above schedules, had stabilized they were exposed to 5 hr of acceleration at 5 G immediately before daily experimental sessions. Food intake was also studied in rats given access to food daily in their home cages and exposed to acceleration immediately before the free-feeding session. Weight gain of free-feeding animals and reinforcement intake of experimental animals dropped after acceleration. Over-all response rate on the FR was depressed markedly by acceleration but local response rates did not appear to be affected. IRT distributions of DRL sessions after acceleration were markedly shifted toward the long intervals. A sequential plot of IRTs on acceleration days showed an altered, but relatively stable, temporal patterning of responses followed by an abrupt return to the normal baseline toward the end of the session.     

Schedule-induced licking during multiple schedules

Schedule-induced polydipsia was studied in rats bar pressing under two-component multiple schedules of food reinforcement. The first component of the multiple schedule was a variable-interval 1-min schedule throughout the experiment. The schedule comprising the second component was varied over blocks of sessions in terms of rate and magnitude of reinforcement, and was either variable-interval 3-min (one pellet), variable-interval 3-min (three pellets), variable-interval 1-min (one pellet), or extinction. Water intake per session varied with the rate of reinforcement in the schedule comprising the second component and was highest when the schedule was variable-interval 1-min. Both bar-pressing behavior and licking behavior showed behavioral interactions between the two components of the multiple schedules. With magnitude of reinforcement held constant, a matching relationship was observed between lick rate and reinforcement rate; the relative frequency of licks in the constant component matched the relative frequency of reinforcement in that component. Bar pressing, however, showed only a moderate degree of relativity matching. During the schedule-induced licking, a burst of licking followed each delivery of a pellet (post-prandial drinking). The duration of these bursts of licking was observed to be a function of the inter-reinforcement interval.