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A matching law analysis of the effects of dopamine receptor antagonists.

Herrnstein's matching equation was used to analyze drug effects on performance in random interval reinforcement schedules. Pimozide caused effects compatible with both motor and motivational impairments, in a 5-component multiple schedule, a 3-schedule 3-day cycle (ALT-3), and a 2-schedule 2-day cycle (ALT-2). However, at low doses, both sulpiride and SCH-23390, tested in the ALT-3 and ALT-2 procedures, caused effects compatible with selective motivational impairments. In experiments using the non-multiple schedules, motivational effects increased during the course of the experimental session, under all three drugs. The interpretation of "motor" and "motivational" deficits in the ALT-2 procedure was validated by experiments in which the response-force and deprivation level were systematically varied. The results support the view that dopamine may be involved in the maintenance of rewarded behaviour, but not differentially implicate the D1 or the D2 receptor subtype.

Animals↗

The dorsal bundle extinction effect:dependence on subtle changes in acquisition.

Destruction of the ascending noradrenergic innervation to the forebrain in rats by intracerebral injection of the selective neurotoxin 6-hydroxydopamine (4 microgram in 2 microliter injected bilaterally into the dorsal bundle in the mesencephalon) was found to cause resistance to extinction of a continuously reinforced lever press response. However, this effect occurred only if the lesion were present during acquisition training on the reinforced schedule and not if intact animals were trained and the lesion inflicted after completion of acquisition training and just prior to the extinction phase. Thus, the behavioural effect that manifests itself during extinction appears to be due to subtle changes in the acquisition learning process. This is consistent with the predictions of an attentional theory of noradrenergic function and appears to exclude most other suggested explanations of the dorsal bundle extinction effect.

Animals↗

Clock-delivered reinforcers in conjunctive and interlocking schedules.

The effects of different temporal requirements in conjunctive and interlocking schedules of reinforcement were examined. The compound schedules were arranged so that a reinforcer could be delivered by either a rat's response or a clock. As the temporal requirements increased in the interlocking schedules, the overall rate of responding increased, but the pattern of responding remained relatively unchanged. As the temporal requirement increased in the conjunctive schedules, the overall rate decreased and a pause-and-run pattern of responding emerged. When the response requirement was reduced to one in the conjunctive schedule for one animal, a low and extremely stable rate of responding developed.

Animals↗

Activity analysis of operant behavior following methylphenidate administration.

13 male Long-Evans hooded rats were tested on a CRF-50 reinforcement schedule. Total response time as well as time and total activity responses away from the bar were significantly influenced by injections of methylphenidate (1.2 mg/kg I.P.). In general, the data supported previous findings of reduced response rate to the drug. However, methylphenidate (a CNS stimulant) increased activity that was not related to bar pressing. Analysis of activity response to drug should include total time and activity as well as operant rates.

Animals↗

Ratio size and cocaine concentration effects on oral cocaine-reinforced behavior.

Monkeys were given a choice between cocaine solutions and water under concurrent fixed-ratio reinforcement schedules. The operant response was spout contact. Six rhesus monkeys served as subjects. The cocaine concentration was varied from 0.0125 to 0.8 mg/ml, and the fixed-ratio value was varied from 8 to 128. Cocaine maintained higher response rates than did water over a wide range of conditions. Response rate and number of cocaine deliveries per session were inverted U-shaped functions of concentration. These functions were shifted to the right as the fixed ratio was increased. The number of cocaine deliveries was more persistent as fixed-ratio value was increased when the unit dose was larger rather than smaller. Cocaine consumption was analyzed as a function of unit price (fixed-ratio value divided by cocaine concentration), and unit price accounted for between 77% and 92% of the variance in cocaine consumption for individual monkeys. The current data support the claim that a drug's reinforcing effects increase directly with dose and underscore the need to gather parametric data when examining the effects of experimental manipulations on a drug-reinforced baseline.

Animals↗

Comparative effects of ethanol on motor activity and operant behavior.

Ethanol effects on two types of motor activity and on lever responding for food delivered on a fixed-ratio 20 (FR 20) reinforcement schedule were compared using C57BL/6 (C57) mice. Low doses of ethanol (1-2 g/kg) transiently elevated horizontal activity and high doses (2.5 and 3.0 g/kg) reduced this behavior throughout testing with a slight recovery toward the end of a 16-min test period. In contrast, similar ethanol doses produced a monotonic reduction in both vertical activity and lever responding for food under the FR 20 schedule. The ethanol-induced reduction in FR 20 lever responding was less prolonged than the reduction in vertical activity but was more prolonged than the reduction in horizontal activity. Because vertical activity and lever responding for food delivered on the FR 20 schedule were never elevated, were reduced at ethanol doses that either stimulated or depressed horizontal activity, and were unaffected by low ethanol doses that did not affect horizontal activity, it is unlikely that either are sensitive to the stimulatory effects of ethanol. Accountable mechanisms for the different effects of ethanol on the three behaviors are unknown; however, the present study eliminates ethanol dose, postinjection time, testing time, and food deprivation condition as possible reasons for the differences.

Animals↗

Toward a behavioral toxicology of paint thinner.

Few experiments have been carried out to evaluate the effects of toxic industrial substances such as the solvents on operant behavior. Laboratory rats trained in a mult FR DRL reinforcement schedule showed a differential impairment in performance when exposed to various doses of paint thinner in the experimental chamber, the FR performance being more sensitive to the solvent than DRL responding. Another study of rats working under a FI schedule suggested that the effects of paint thinner are rate-dependent, a finding which suggests a similarity of thinner with the amphetamines in regard to the behavioral effect. Two other experiments addressed to the behavioral effects of chronic exposure to the solvent showed a decrease in locomotor activity and an impaired acquisition of a complex temporal discrimination task in laboratory rats exposed to paint thinner during four, eight of sixteen weeks. These findings are suggestive of brain dysfunction associated with thinner inhalation but further experiments are needed for more definite conclusions.

Amphetamine↗

The effects of lesions of the habenula nucleus on lever press behaviour during a tandem operant schedule with contrasting response requirements.

The effect of bilateral lesions of the habenula nuclei in male Lister hooded rats was assessed in performance of a well learned complex tandem operant reinforcement schedule. The schedule requirement involved two successive and contrasting components in which 15 operant lever press responses followed by inhibition of the same response for a period of 15 s provided liquid-food reinforcement. Initially little disruption of performance was seen when each component of the schedule was differentially signalled with an external cue. However, relative to controls, lesioned animals showed an increasing disruption of performance when such cues were omitted. The deficit in performance of lesioned animals was not a simple failure to inhibit responding that could be predicted from an altered input from septal areas. It is suggested that these behavioural data are consistent with the anatomical evidence for the habenula as a functional relay for the integration of information from limbic structures and the striatum and that lesions of the habenula affect the ability of animals to maintain effective response strategies, particularly when these are under intrinsic control.

Animals↗

Late post-learning participation of entorhinal cortex in memory processes.

Mice of the BALB/c strain were bilaterally implanted with electrodes in the lateral entorhinal cortex (EC) in order to study the influence of post-trial EC stimulation on memory. The learning task was a food reinforced operant conditioning. At one of several time intervals after a first learning session, the experimental groups were stimulated for 80 s with subseizure current intensity. Testing was carried out 24 h later. In the first experiment, a continuous reinforcement schedule was used. EC stimulation had no effect when applied at the 30-s or 3-h intervals, but surprisingly a 30-min delayed stimulation greatly improved retention compared to performance of non-stimulated animals. In the second experiment, the same paradigm was used in a discriminative operant conditioning task. The same facilitation on retention was observed only with the 30-min delayed stimulation. Compared to previous data with hippocampal or hypothalamic stimulation, the present results reveal that EC is lately involved in memory processes.

Animals↗

Intracerebral self-administration of the cannabinoid receptor agonist CP 55,940 in the rat: interaction with the opioid system.

The effect of CP 55,940 [(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclo-hesanol], heroin and etonitazene on intracerebroventricular (i.c.v.) self-administration in a free-choice procedure was evaluated in rats. Animals were trained in 1-h daily sessions with a continuous reinforcement schedule to press two active levers to obtain the vehicle of each drug. Then, when a stable baseline was reached, each drug could be self-administered by pressing the lever found to be less preferred during training, while the vehicle came from the other. The number of bar pressings associated with the delivery of increasing unit doses of CP 55,940 (0.1, 0.2, 0.4, 0.8, 1.6 microg/2 microl/infusion), heroin (0.125, 0.25, 0.5, 1, 2 microg/2 microl/infusion) or etonitazene (0.1--0.2--0.5--1 microg/ 2 microl/infusion) and with the delivery of the corresponding vehicle was fitted by symmetrical parabolas. The mean drug intake was linearly related to the log of self-administered drugs. Pretreatment with SR141716A [N-piperidino-5-(4-chlorophenyl)1-(2,4-dichloro-phenyl)-4-methylpyrazole-3-carboxamide] (0.5 mg/kg) or naloxone HCl (2 mg/kg/i.p.) 15 min before each daily session reduced the self-administration of both CP 55,940 and heroin. The combination of CP 55,940 with heroin or etonitazene reduced the number of drug-associated lever pressings compared to that obtained with the maximal reinforcing unit dose of each drug alone. These findings suggest there may be a strong interaction between opioids and the cannabinoid system.

Analgesics↗

Some effects of chlordiazepoxide and d-amphetamine on response force during punished responding in rats.

Rats were reinforced with water on a continuous reinforcement schedule and were also punished with electric shock for every fifth response applied to a silent, isometric, force-sensing manipulandum. Oral doses of chlordiazepoxide (3.0, 9.0, 27.0 mg/kg) increased both conventional rate and force of punished responding. In contrast, d-amphetamine (0.8, 1.6, 3.2 mg/kg, by gavage) further decreased conventional rate and force of response, but this latter drug increased the rate of recorded responses that were lower than the 15-g force criterion for response consequences. The results for chlordiazepoxide are viewed in terms of its anxiolytic properties, while the d-amphetamine data appear to support a theory of amphetamine effects based on the concept of stereotyped behaviors.

Animals↗

Acute stress reduces reward responsiveness: implications for depression.

BACKGROUND: Stress, one of the strongest risk factors for depression, has been linked to "anhedonic" behavior and dysfunctional reward-related neural circuitry in preclinical models. METHODS: To test if acute stress reduces reward responsiveness (i.e., the ability to modulate behavior as a function of past reward), a signal-detection task coupled with a differential reinforcement schedule was utilized. Eighty female participants completed the task under both a stress condition, either threat-of-shock (n = 38) or negative performance feedback (n = 42), and a no-stress condition. RESULTS: Stress increased negative affect and anxiety. As hypothesized based on preclinical findings, stress, particularly the threat-of-shock condition, impaired reward responsiveness. Regression analyses indicate that self-report measures of anhedonia predicted stress-induced hedonic deficits even after controlling for anxiety symptoms. CONCLUSIONS: These findings indicate that acute stress reduces reward responsiveness, particularly in individuals with anhedonic symptoms. Stress-induced hedonic deficit is a promising candidate mechanism linking stressful experiences to depression.

Adolescent↗

Delayed reinforcement in a multiple schedule.

Three rats and a pigeon were first trained on a two-component multiple schedule in which reinforcement in the two components occurred immediately after a response. Later, reinforcement in one component was delayed by a few seconds. During both stages of the experiment, reinforcement was scheduled by equal variable- (pigeon) or random-interval (rats) schedules in the two components. The main effect of the delayed reinforcement was to increase the rate of responding in the unchanged (non-delay) component. This behavioral contrast effect did not appear in all cases to be dependent upon a reduction in the rate of responding or the frequency of reinforcement in the delay component. This finding suggests that a reduction in response rate and/or reinforcement frequency in one component of a multiple schedule may not be a necessary prerequisite for the occurrence of behavioral contrast. This finding is, however, consistent with an explanation that suggests that behavioral contrast results from the introduction of a less-preferred condition in one component of a multiple schedule, since it is known that animals "prefer" immediate to delayed reinforcement.

Journal Article↗

Toward an animal model of type A behavior.

Time estimation and dominance tests were used to differentiate the behavior of Mongolian gerbils to be analogous to Type A and Type B human behavior. Preliminary classification of animals as "Type A" or "B" was based upon differential performance on DRL 20-sec and DRL 60-sec reinforcement schedules. To retain their preliminary classification, Type A and Type B animals were required to be dominant and subordinate, respectively, in matches with each of three same-sex animals of opposite behavioral classification. Following classification, breeding pairs were constituted and classification procedures were repeated with two succeeding generations. Animals that exhibited Type A timing "won" significantly more dominance matches than did Type B animals. Incidence rates of Type A and Type B behavior in the two selectively bred generations were significantly greater than frequencies in the original stock generation. The usefulness of the present animal model for investigating the association of Type A behavior with coronary heart disease is discussed.

Animals↗

A reinterpretation of schedule-induced behaviors based on a systematic analysis of behavior.

Confusion exists regarding the criteria to be used in determining whether or not particular behaviors are schedule-induced. Four critical characteristics of schedule-induced behaviors are suggested and a comparison made of the complete range of behaviors exhibited by body weight-reduced rats drinking in response to one of three stimuli. These were (1) a fixed-time food reinforcement schedule, (2) a meal of dry food, and (3) 24 hour water deprivation. Drinking, locomotion, rearing and oral and perioral behaviors occurred in accordance with the defining characteristics of schedule-induced behaviors. Rats in the fixed-time reinforcement condition also deposited significantly greater numbers of fecal boli. Sniffing and food bowl related behaviors occurred as terminal responses for this group. It is concluded that animals which receive reinforcers intermittently maintain high levels of arousal for extended periods, and that the presence of the schedule may mimic conditions experienced by wild rats in non-laboratory settings. In such conditions ambulatory behaviors may be particularly adaptive. In contrast, reinforcing sensory feedback and a stress reducing role may be particularly important in the mediation of oral behaviors (such as drinking) which occur during intermittent reinforcement.

Animals↗

Cocaine self-injection behaviour under schedules of delayed reinforcement in monkeys.

Rates of lever pressing, maintained either by response-dependent intravenous injections of cocaine (250 mug/kg per injection) or by food-pellet presentation, were compared and found to vary systematically as a function of the delay (5-100 s) imposed between the response(s) and the occurrence of reinforcement. The control of responding by two schedules of delayed reinforcement was studied. The first scedule permitted responses to occur during the delay period without any programmed consequence; the second schedule required a response, and then the elapse of x seconds without any additional response(s). At imposed delays of 50 and 100 s, response rates were reduced significantly when the second schedule was in effect by comparison with the first. The effect was observed when responding was maintained either by intravenous cocaine injections or by food-pellet presentation. Across all comparable conditions, response rates were higher when maintained by scheduled cocaine injections than by food pellets. Rate enhancement, generally induced by drugs of the psychomotor stimulant type, could account for the observed difference.

Animals↗

A pitfall for the expectancy theory of human eyelid conditioning.

Two simple eyeblink conditioning experiments with random intermittent reinforcement schedules were performed. In Experiment 1, subjects had to rate their expectancy for an unconditioned stimulus (US) on a seven-level scale prior to each trial. As anticipated, expectancy for US increased with a successive conditioned stimulus (CS) alone, and decreased with successive CS-US pairings. However, Experiments 1 and 2 showed that the frequency of eyeblink conditioned responses (CRs) evolved in a direction opposite to that of expectancy changes: CRs increased, whereas expectancy for US decreased, and vice versa. The possible effect of sensitization on eyeblink response was ruled out by the lack of a run effect in an unpaired control group in Experiment 2. These results tend to disconfirm the expectancy theory of conditioning. Although they were explicitly predicted by the conventional "strength" theory of conditioning, an alternative interpretation is proposed within a cognitive framework.

Adult↗

Bisection of temporal intervals by pigeons.

Two experiments investigated temporal bisection in pigeons using a procedure similar to that of Stubbs (1976). This procedure measures the point in time at which the bird switches from the shorter to the longer valued of two fixed-interval reinforcement schedules with a common starting point. The first experiment substantiated previous findings of switching at the geometric mean of the two interval values and strengthened identification of this switching with bisection by eliminating the possibility that the birds simply switched to the longer interval when the shorter one was perceived to have expired. The experiment also extended the range of values for which temporal intervals have been found to be bisected at their geometric mean. A second experiment demonstrated that the usefulness of the present procedure for determining temporal bisection points is limited to cases in which the longer interval is no more than four times the duration of the shorter interval. Greater separation of the two interval durations produced a period of nonresponding during which the location of the switching or bisection point was totally ambiguous.

Animals↗