Effects of d-amphetamine and pentobarbital under concurrent fixed-ratio schedules.

Pigeons were studied under a two-key concurrent fixed-ratio schedule of food presentation. During the first five sessions, the fixed-ratio requirements were 30 responses on one key (major key) and 120 responses on the other key (minor key): responding occurred almost exclusively on the major key. When the fixed-ratio requirements were then made equal at 30 responses on both keys, responding continued to predominate on the major key. The asymmetric distribution of responses persisted when the concurrent fixed-ratio fixed-ratio schedule was interrupted with periods during which the major key was associated with extinction while the other key remained associated with a fixed-ratio schedule. Additionally, in some subjects the fixed-ratio requirements were increased. These schedule modifications decreased the asymmetry in responding but did not eliminate it. d-Amphetamine decreased rates on both keys and slightly increased the asymmetric distribution of responses, while pentobarbital reversed the distribution of responses by increasing low rates and decreasing high rates. The pigeons maintained their original asymmetric distribution of responses during the 1 1/2-year-long study, despite schedule alterations and drug administrations.     

Effects of schedule of reinforcement on a pentobarbital discrimination in rats.

The purpose of this study was to determine the effects of the schedule of reinforcement on a pentobarbital discrimination in rats. Five rats were trained to discriminate 10 mg/kg pentobarbital from saline under a multiple fixed-interval 180-s fixed-ratio 20 schedule of reinforcement. During both saline and pentobarbital training sessions, subjects emitted a higher percentage of correct responses under the fixed-ratio component as compared to the fixed-interval component of the multiple schedule. Determination of the pentobarbital dose-response curve under the fixed-ratio component resulted in a steep curve characterized by responding on the saline lever at low doses and on the drug lever at higher doses. Under the fixed-interval component, a graded dose-effect curve was produced, with considerable responding on both levers after intermediate doses of pentobarbital. The administration of phencyclidine and MK-801 resulted in an intermediate level of drug-lever responding for some subjects. Administration of d-amphetamine resulted in saline (nondrug) appropriate responding. The results of this study demonstrate that the schedule of reinforcement is a determinant of drug stimulus control, just as it is a determinant of other drug effects.     

Oral self-administration of pentobarbital by rhesus monkeys: relative reinforcing effects under concurrent fixed-ratio schedules.

During daily 3-hr sessions, orally delivered pentobarbital solutions and water, or two separate pentobarbital solutions, were concurrently available to rhesus monkeys according to fixed-ratio schedules of mouth contacts with a spout. First water, and then each of four "comparison-concentration" pentobarbital solutions (0.0625, 0.25, 1, and 4 mg/mL), was successively available from one spout for a block of sessions under a fixed-ratio-64 (three monkeys) or fixed-ratio-16 (one monkey) schedule. Under an identically sized fixed-ratio schedule, deliveries of a "standard-concentration" pentobarbital solution were concurrently available from a second spout. The concentration of the standard solution remained unchanged throughout testing of the series of comparison solutions. Each of three pentobarbital concentrations (4, 1, and 0.25 mg/mL) in turn served as the standard concentration. Within each pair of concurrently available solutions, the higher drug concentration maintained more behavior than the lower concentration. Thus when monkeys were provided with concurrent access to different pentobarbital concentrations, relative reinforcing effects were directly related to drug concentration. Further, the amount of behavior maintained by a particular drug concentration was dependent on the concentration of the concurrently available drug solution. Thus, the relative effectiveness of a reinforcer in maintaining behavior is a function of both the reinforcer's magnitude and the availability of alternative reinforcers in the environment.     

Learning about water by hungry rats

In Experiments 1 and 2 hungry rats were trained in a straight alley with consistent food reward (FF), food and nonreward trials intermixed (FN), or food and water trials intermixed (FW). In Experiment 1 rats were tested with nonrewarded trials (extinction) and Groups FN and FW did not differ, both running faster then Group FF. In Experiment 2 rats were tested with consistent water reward, and Group FW ran faster then Group FN, which was superior to Group FF. In Experiment 3, one group of hungry rats was trained on a single alternating schedule of food and water in Phase 1 and was shifted to a single alternating schedule of food and nonreward in Phase 2 (Group FW); the second group (Group FN) received a single alternating schedule of food and nonreward in both phases. When Group FW was shifted to nonreward from water, performance to nonreward was temporarily disrupted. These results indicate that, contrary to previous conclusions, hungry rats can learn about water when drive is strong and food is received in the situation.     

Punishment of responding under schedules of stimulus-shock termination: effects of d-amphetamine and pentobarbital.

Responding maintained in squirrel monkeys under 5-min fixes-interval schedules of either food presentation or termination of a visual stimulus associated with electric-shock delivery was suppressed by presenting an electric shock for every thirtieth response (punishment). In monkeys responding under the schedule of food presentation, d-amphetamine sulfate only further decreased punished responding, and pentobarbital sodium markedly increased punished responding, as expected from previous reports. In monkeys responding under the schedule of stimulus-shock termination, however, the effects of the two drugs were opposite: d-amphetamine markedly increased punished responding, whereas pentobarbital only decreased responding. Thus, the effects of these drugs on punished responding were different depending on the type of event maintaining responding. These and previous results indicate that it may be misleading and inaccurate to speak of the effects of drugs on "punished responding" as though punishment were a unitary phenomenon. As with any behavior, the effects of drugs and other interventions on punished responding cannot be accurately characterized independently of the precise conditions under which the behavior occurs.     

Two time windows of anisomycin-induced amnesia for inhibitory avoidance training in rats: protection from amnesia by pretraining but not pre-exposure to the task apparatus

We have studied the effect of training conditions on hippocampal protein synthesis-dependent processes in consolidation of the inhibitory avoidance task. Adult male Wistar rats were trained and tested in a step-down inhibitory avoidance task (0.4 mA foot shock, 24 hr training–test interval). Fifteen minutes before or 0, 3, or 6 hr after training, animals received a 0.8-μl intrahippocampal infusion of the protein-synthesis inhibitor anisomycin (80 μg) or vehicle (PBS, pH 7.4). The infusion of anisomycin impaired retention test performance in animals injected 15 min before and 3 hr after the training session, but not at 0 or 6 h post-training. Pretraining with a low foot shock intensity (0.2 mA) 24 hr before training, prevented the amnestic effect of anisomycin injected at 15 min before or 3 hr after training. However, simple pre-exposure to the inhibitory avoidance apparatus did not alter the amestic effects of anisomycin. The results suggest that hippocampal protein synthesis is critical in two periods, around the time of, and 3 hr after training. A prior weak training session, however, which does not itself alter step-down latencies, is sufficient to prevent the amnestic effect of anisomycin, suggesting that even if not behaviorally detectable, weak training must be sufficient to produce some lasting cellular expression of the experience.     

Effects of promazine, chlorpromazine, d-amphetamine, and pentobarbital on treadle pressing by pigeons under a signalled shock-postponement schedule.

The effects of promazine on treadle pressing to postpone the presentation of electric shock were studied in three pigeons. The effects of chlorpromazine, d-amphetamine, and pentobarbital were studied in two of these pigeons. Each treadle press postponed electric shock for 20 sec and presentation of a preshock stimulus for 14 sec. Selected doses of both promazine and chlorpromazine increased the rates of treadle pressing in all birds. The response-rate increases produced by promazine and chlorpromazine were due to increased conditional probabilities of treadle pressing both before and during the preshock stimulus. d-Amphetamine (1 and 3 mg/kg) slightly increased responding in one of the birds, but not to the extent that promazine or chlorpromazine did. In the other bird, the 10 mg/kg dose of d-amphetamine increased shock rate but did not change response rate. Some doses of d-amphetamine increased the conditional probabilities of responding both in the absence of the preshock signal and during the preshock signal in both birds. Pentobarbital only decreased response rates and increased shock rates.     

Retrograde amnesia for visual memories after hippocampal damage in rats

It is generally believed that the hippocampus is not required for simple discrimination learning. However, a small number of studies have shown that hippocampus damage impairs retention of a previously learned visual discrimination task. We propose that, although simple discrimination learning may proceed in the absence of the hippocampus, it plays an important role in this type of learning when it is intact. In order to test the role of the hippocampus in simple discrimination learning, we performed a series of experiments utilizing a two-choice picture discrimination task. Our experiments confirm that rats readily learn simple two-choice picture discriminations after hippocampus damage. However, if such discriminations are first learned while the hippocampus is intact, subsequent hippocampus damage causes severe retrograde amnesia for the discriminations. Furthermore, retrograde amnesia for simple picture discriminations was equally severe when the interval between training and damage was 1 d or 60 d; remote picture memories are not spared. Similarly, the rule or schema underlying a recently or remotely acquired picture discrimination learning set was lost after hippocampus damage. The severity of retrograde amnesia for simple picture discriminations is negatively correlated with the volume of spared hippocampus tissue. Thus, the hippocampus plays an essential role in long-term memories supporting simple picture discriminations.     

Priming of face matching in amnesia.

Priming was studied in a task that required a speeded response to photographs of faces. On each trial, subjects viewed two faces and decided if the same person was shown twice or if two different people were shown. Both familiar and unfamiliar (i.e., well-known and unknown) faces were used, and some face pairs were repeated with a mean delay of about 10 min. Repetition was associated with faster reaction times in young subjects (Experiment 1) as well as in amnesic patients and age-matched control subjects (Experiment 2). The patients' reaction times were slower overall, although the magnitude of the priming effect did not differ from that in the control subjects. This preservation of a normal reaction-time facilitation in subjects with impaired recognition memory for faces occurred for both familiar and unfamiliar faces, suggesting that amnesia does not necessarily interfere with the acquisition of new information as indexed by this priming effect.     

Release from proactive interference by experimental amnesia: electroconvulsive shock improves radial-arm maze performance in rats

Rats were trained in an eight-arm radial maze and tested using a proactive interference (PI) procedure. Each test trial consisted of forced choices of four randomly selected arms followed, after a 2-h delay, by free choices among all eight arms. Normally, rats chose correctly during the free choices by entering and retrieving food from the four arms not yet visited during the test trial. Occasionally, an interference trial preceded the test trial by 1.5 or 3 h; interference trials consisted of forced choices of another four arms and an immediate test. The presence of an interference trial lowered test-trial performance (PI). Electroconvulsive shock (ECS) administered immediately after the interference trial had no effect; i.e., PI was still observed. When ECS was administered at the midpoint of the 3-h intertrial interval, performance increased to control (no ECS, no PI) levels. Such release from PI, however, was not obtained, and test-trial performance remained inaccurate when ECS was delivered immediately after the forced choices of the test trial (either 1.5 or 3 h after the interference trial).     

Somatic and autonomic indexes of recovery from electroconvulsive shock-induced amnesia in rats

Autonomic response indexes of experimental amnesia have recently been found to have higher electroconvulsive shock (ECS) intensity thresholds and steeper retrograde gradients than have traditional somatic indexes. The present studies examined the hypothesis that recovery from somatically indexed experimental amnesia depends upon the existence of autonomically available residual memory. In a between-subjects design, a 200-mA ECS was used to produce amnesia for a tone-footshock pairing as indicated by lick suppression, defection, and bradycardia. The next day, these amnesic animals received a reminder footshock outside of the training apparatus, which was found to restore memory on a test trial 24 hr later. The behavior of control groups indicated that this reminder effect was due to the restoration of specific memory rather than systemic consequences of treatment. With a within-subjects design, a second experiment obtained a reminder effect in animals individually shown to be "fully" amnesic by all three response indexes monitored. A third experiment varied the intensity of the reminder footshock and revealed that the different memory indexes examined do not have reminder-footshock thresholds inversely related to their initial resistance to amnesia. The results support a retrieval-failure view of experimental amnesia and suggest that the same fundamental physiological processes underlie both autonomically indexed memory and somatically indexed memory.