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Mother rats bar-press for pups: effects of lesions of the mpoa and limbic sites on maternal behavior and operant responding for pup-reinforcement.

This series of studies explored the operant response rates for pup-reinforcement of female Sprague Dawley rats that were either postpartum or cycling and sustained lesions of the medial preoptic area (mpoa), the lateral amygdala, the nucleus accumbens, or sham lesions. The last experiment tested the effects on operant responding of preventing direct access to pups in mpoa and sham-lesioned postpartum mothers. All animals were trained prior to mating on an FR-1 bar-press schedule to criterion (50 presses in 30 min) for a food (Froot Loops) reward in an operant chamber. At the end of pregnancy animals that were to be tested postpartum were provided in their home cages with six newborn foster pups; mother-litter interactions were observed on the last 3 days of pregnancy and throughout the postpartum period. On each of these same days after a period of separation from pups, females were tested in the operant box for delivery of rat pups. With each bar-press response, a rat pup rather than a Fruit Loop was delivered down a gentle shoot into the hopper. Non-postpartum, but maternal, multiparous animals who were showing estrous cycles were tested using the same procedures. The first and second studies showed that animals (both postpartum and as cycling multiparous animals) with mpoa lesions exhibited a significant reduction in bar-press rate for pup reinforcement in the operant box. In postpartum animals, amygdala lesions also produced a bar-press deficit, whereas nucleus accumbens lesions did not. All lesioned groups showed deficits in maternal responding in the home cage and deficits in retrieval in the operant box. These results indicate that systems associated with the mpoa mediate both the stereotypical maternal behaviors and pup-reinforcement. In contrast, the expression of home cage maternal behavior is dependent on the integrity of both the amygdala and nucleus accumbens, whereas operant responding need not be. These results indicate a dissociation of mechanisms mediating expression of the species-typical maternal behavior and pup-reinforcement.

Amygdala↗

Modulation of memory, reinforcement and anxiety parameters by intra-amygdala injection of cholecystokinin-fragments Boc-CCK-4 and CCK-8s.

This series of experiments examined the effects of the cholecystokinin (CCK) fragments Boc-CCK-4 and CCK-8s on memory, reinforcement and anxiety following unilateral injection into the central nucleus of the amygdala (CeA). In experiment 1, rats with chronically implanted cannulae were injected with CCK-8s or Boc-CCK-4 and were tested on a one-trial uphill avoidance task. Post-trial injection of 20 ng Boc-CCK-4 or 1 ng CCK-8s was found to improve the retention performance, whereas lower and higher doses had no effect. The hypermnestic effects of Boc-CCK-4 and CCK-8s were no longer evident when injection was performed 5 h, rather than immediately, after the learning trial. In experiment 2, the elevated plus-maze was used to gauge anxiogenous properties of intra-amygdala injections of Boc-CCK-4 and CCK-8s in memory-enhancing doses. The treatment with 20 ng Boc-CCK-4 and 1 ng CCK-8s did not influence the number of entries into and time spent on the open and enclosed arms of the maze as well as other anxiety-related behaviors. In experiment 3, possible reinforcing effects of the CCK-fragments were examined. After intra-amygdala injection of Boc-CCK-4 or CCK-8s in memory-enhancing doses the rats were placed into one of four restricted quadrants of a circular open field (closed corral) for a single conditioning trial. Subsequent tests for conditioned corral preference revealed no evidence for reinforcing or aversive effects of the CCK-fragments. In sum, these findings indicate that Boc-CCK-4 and CCK-8s facilitate memory processing upon injection into the CeA without exerting reinforcing or anxiogenous effects.

Amygdala↗

Forward propagating reinforcement learning--biologically plausible learning method for multi-layer networks.

We introduce a biologically plausible method of implementing reinforcement learning to multi-layer neural networks. The key idea is to spatially localize the synaptic modulation induced by reinforcement signals, proceeding downstream from the initial layer to the final layer. Since reinforcement signals are known to be broadcast signals in the actual brain, we need two key assumptions, inhibitory backward connections and bypass to output units, to spatially localize the effect of delayed reinforcement without breaking the basic laws of neurophysiology.

Animals↗

Behavioral reinforcement of long-term potentiation is impaired in aged rats with cognitive deficiencies.

Behavioral stimuli with emotional/motivational content can reinforce long-term potentiation in the dentate gyrus, if presented within a distinct time window. A similar effect can be obtained by stimulating the basolateral amygdala, a limbic structure related to emotions. We have previously shown that aging impairs amygdala-hippocampus interactions during long-term potentiation. In this report we show that behavioral reinforcement of long-term potentiation is also impaired in aged rats with cognitive deficits. While among young water-deprived animals drinking 15 min after induction of long-term potentiation leads to a significant prolongation of potentiation, cognitively impaired aged rats are devoid of such reinforcing effects. In contrast, a slight but statistically significant depression develops after drinking in this group of animals. We suggest that an impaired mechanism of emotional/motivational reinforcement of synaptic plasticity might be functionally related to the cognitive deficits shown by aged animals.

Aging↗

Relationships between binge drinking and substance-free reinforcement in a sample of college students: a preliminary investigation.

Heavy episodic drinking is a relatively common phenomenon among college students, and students who engage in binge drinking are at increased risk for a variety of adverse consequences. This paper investigates relationships between substance use and reinforcement derived from specific categories of substance-free activities among a sample of 256 college undergraduates. Data from a standardized behavioral inventory were used to compare the frequency, pleasure, and reinforcement potential of substance-free events and activities experienced by binge drinkers and a comparison group. Binge drinkers reported significantly lower scores across a variety of substance-free activity categories and, in the majority of the cases, the relationship between binge drinking and decreased reinforcement density remained significant after accounting for the effects of the use of other drugs and demographic variables. These results are consistent with a growing body of evidence linking substance use to deprivation of substance-free reinforcement.

Adolescent↗

The effects of chronic morphine on behavior reinforced by several opioids or by cocaine in rhesus monkeys.

The reinforcing effects of intravenously delivered cocaine, alfentanil, morphine, heroin, nalbuphine, or buprenorphine were evaluated in four rhesus monkeys before, during, and after daily administration of 3.2 mg/kg morphine. Morphine was given 21 h prior to measures of the reinforcing effects of each of the drugs. No changes in the potency of cocaine or the high efficacy mu agonist alfentanil were detectable during the period of chronic morphine administration. Small (1/2-1) log unit decreases in the reinforcing potency of intermediate efficacy mu agonists morphine and heroin occurred during chronic morphine administration. Larger decreases in both the potency and effectiveness of low-efficacy mu agonists nalbuphine and buprenorphine developed during this time. These data suggest that the amount of tolerance that develops to the reinforcing effects of opioids depends on the efficacy of the drugs used to maintain responding.

Alfentanil↗

Reinforcing, subjective, and physiological effects of MDMA in humans: a comparison with d-amphetamine and mCPP.

3,4-methylenedioxymethamphetamine (MDMA) is a widely used drug of abuse chemically related to both the amphetamines and mescaline. Laboratory animal studies have shown that MDMA is a potent re-uptake inhibitor and releaser of dopamine and serotonin. Although the subjective and physiological effects of MDMA have been compared to d-amphetamine in humans, no direct comparison with a serotonin releasing agent has been reported and reinforcing effects have not been evaluated. In this paper we report a direct comparison of the reinforcing, subjective, and physiological effects of MDMA (1 and 2 mg/kg) to d-amphetamine (10 and 20 mg), to metachlorophenylpiperazine (mCPP--a serotonin releasing agent (0.5 and 0.75 mg/kg)), and to placebo using a within-subject design in 12 volunteers with moderate MDMA experience. Both the high dose of d-amphetamine and MDMA showed significant reinforcing effects as indicated by high cross-over values on the multiple choice procedure compared to all other treatments. All three drugs showed dose-dependent changes in subjective effects whereas physiological effects were most pronounced for MDMA with almost no changes seen with mCPP. The subjective effects of MDMA were similar both to those of mCPP and d-amphetamine, suggesting that both dopamine and serotonin systems are involved in mediating these effects. In contrast, only the dopaminergic agents, d-amphetamine and MDMA, had reinforcing effects.

Adolescent↗

Comparison of the intravenous reinforcing effects of propofol and methohexital in baboons.

Propofol is a widely used intravenous anesthetic that can directly activate and positively modulate the GABA(A)-receptor. Propofol is not currently regulated under the USA Controlled Substances Act. The present study evaluated the intravenous reinforcing effects of propofol compared to the intravenous barbiturate anesthetic methohexital in baboons using a procedure in which doses of the test drug were substituted for a standard cocaine dose. Drug or vehicle was available for self-injection during daily 5.5-h sessions under a fixed-ratio 120 or 160 schedule of reinforcement. A 40-min timeout after each injection limited the maximum of injections per session to eight. Food pellets were available continuously during the session under a fixed ratio 10 schedule of reinforcement. Self-injection of cocaine (0.001-0.32 mg/kg/injection) and vehicle was characterized first. Cocaine maintained self-injection in a dose-dependent manner, with peak injections maintained by 0.32 mg/kg. Vehicle and each dose of propofol (0.1-1.0 mg/kg/injection) and methohexital (0.01-1.0 mg/kg/injection) were substituted for 0.32 mg/kg cocaine for at least 10 sessions. Propofol and methohexital maintained self-injection greater than vehicle in all three baboons, and these effects were dose dependent. Methohexital maintained peak mean levels of self-injection that were >6 injections/day at doses of 0.56 and 1.0 mg/kg, and did not alter food intake systematically. Propofol maintained peak mean levels of self-injection at 1.0 mg/kg that ranged from 2.2 to >6 injections/day across the baboons. Food intake was increased slightly above vehicle levels by propofol self-injection in two baboons, and was decreased in the third baboon. These data indicate that propofol, like methohexital, can function as a positive reinforcer.

Anesthetics, Intravenous↗

A brief method for conducting a negative-reinforcement assessment.

A brief negative-reinforcement assessment was conducted with developmentally disabled children with severe destructive behavior. Five children were trained to engage in a simple escape response (e.g., a hand clap). Then each child was presented with a variety of stimuli or tasks that ranged on a scale from preferred to nonpreferred, based on parent ranking. The participant received a brief break from the stimuli or task, contingent on each escape response. For one child, an avoidance contingency was also implemented in which he could engage in the response to avoid the presentation of stimuli. Results showed that for each child, several stimuli were identified that may serve as effective negative reinforcers. Results also indicated that the procedure did not elicit any negative side effects for four children and low rates of destructive behavior for the fifth child. For one child, the results of the negative-reinforcement assessment were used to develop an effective treatment for destructive behavior. Additional applications of the reinforcement assessment to treatment interventions is discussed, as well as limitations to the procedure.

Adolescent↗

Sequential evaluation of reinforced compliance and graduated request delivery for the treatment of noncompliance in children with developmental disabilities.

Errorless compliance training is a recently developed approach that has been demonstrated to be effective in treating severe oppositional behavior in children. In conjunction with several ancillary techniques, the approach comprises two fundamental components: reinforcement for child compliance and delivery of requests in a four-level hierarchy, from requests that yield high levels of compliance to those that yield low levels. To determine the relative contribution of each component, four children with developmental disabilities and severe oppositional behavior were observationally assessed in baseline and then treated using reinforcement following each instance of compliance to parental requests. Following this first treatment phase, we used the graduated request hierarchy in conjunction with reinforced compliance. Results indicated that use of reinforcement for compliance in isolation was ineffective in bringing about clinically significant improvements in child compliance. The addition of the graduated request hierarchy appeared to be associated with substantial changes in child compliance that maintained in follow-up assessments.

Behavior Therapy↗

Interactions between neurons in the amygdala and hypothalamus during conditioned reflex behavior involving choice of reinforcement quality in cats.

The organization of distributed amygdalo-hypothalamic and local amygdalar and hypothalamic neural networks was studied in three cats, trained to perform a food-related operant conditioned reflex to light by the "active choice" of reinforcement quality method; pressing the pedal with a short latent period provided the cats with a bread/meat mixture, while pressing with a long latent period yielded meat. Animals showed sharp differences in their individual abilities to choose one or the other reinforcement. Two cats preferred long-latency pedal-pressing to obtain meat, and were considered to be "self-controlled," while the third cat, which preferred short-latency pedal-pressing to obtain the less valuable reinforcement (the bread/meat mixture) was described as "impulsive." Chronically implanted semimicroelectrodes were used to record multineuron activity in the basolateral nucleus of the amygdala and the lateral nucleus of the hypothalamus. Interactions between the discharge trains of neighboring and distant neurons were assessed by cross-correlation analysis. Interneuron functional connections were found to predominate significantly in the local neural networks of the basolateral amygdala and distributed amygdalar-hypothalamic networks in the "impulsive" animal as compared with the "self-controlled" animals, suggesting a role for these types of connection in forming the individual characteristics of higher nervous activity. The identical incidences of interneuron interactions in the lateral nucleus of the hypothalamus in cats with different individual preferences suggest that local networks in this formation are not involved in analyzing reinforcement quality.

Amygdala↗

Contrast, component duration, and the following schedule of reinforcement.

Experiment 1 investigated component duration in a four-component multiple schedule designed to separate the effects of the preceding schedule of reinforcement from those of the following schedule of reinforcement. The preceding schedule in the preceding component had no consistent effect regardless of component duration. The following schedule was a powerful determinant of behavior, however, with higher response rates resulting from a following period of extinction. Moreover, the effect of the following schedule was greater with short component durations, which strongly suggests that component-duration effects previously found with multiple schedules are due generally to variation in the degree of control by the following schedule. Experiments 2--4 investigated the basis of the effects of the following schedule. In some situations differential responding in the following component was the controlling variable, but in others it was differential reinforcement in the following component. The results are consistent with the view that response rate during a stimulus is inversely related to the "value" of the following component, where the calculation of value must include both primary and conditioned reinforcement.

Animals↗

Acute nicotine reinforcement, but not chronic tolerance, predicts withdrawal and relapse after quitting smoking.

Little research has examined the association of tobacco dependence with nicotine tolerance or reinforcement in a clinical sample. Smokers preparing to quit smoking participated in laboratory sessions to assess nicotine tolerance on subjective, cardiovascular, and performance measures and to assess nicotine reinforcement using a choice procedure. Participants were then provided with individual counseling (but no medication), made a quit attempt, and were followed for 1 year to determine clinical outcome, as determined by postquit withdrawal and days to relapse. Nicotine tolerance was unrelated to either withdrawal or relapse. However, acute nicotine reinforcement was significantly related to both greater withdrawal and faster relapse. Results challenge the common assumption that nicotine tolerance is closely related to dependence but suggest that nicotine reinforcement may have theoretical and clinical significance for dependence.

Administration, Intranasal↗

Rhinal cortex ablations fail to disrupt reinforcer devaluation effects in rhesus monkeys (Macaca mulatta).

Studies have shown that excitotoxic lesions of the amygdala attenuate reinforcer devaluation effects in monkeys and rats. Because the rhinal (i.e., entorhinal and perirhinal) cortex has prominent reciprocal connections with the amygdala and has been suggested to store knowledge about objects, it is possible that it too composes part of the critical circuitry subserving learning about objects and their associated reinforcement value. To test this possibility, rhesus monkeys with rhinal cortex removals as well as unoperated controls were tested using a reinforcer devaluation procedure. Monkeys with rhinal cortex removals and controls, unlike those with amygdala lesions, tended to avoid displacing objects overlying a devalued food. These results indicate that the rhinal cortex is not a critical part of the neural circuitry mediating the effects of reinforcer devaluation.

Analysis of Variance↗

Self-administration of cocaine, alfentanil, and nalbuphine under progressive-ratio schedules: consumer demand and labor supply analyses of relative reinforcing effectiveness.

Progressive-ratio (PR) schedules of intravenous (i.v.) drug self-administration are useful for establishing the relationships between reinforcing effectiveness and pharmacological actions of abused drugs. The authors compared the reinforcing effects of the high-efficacy opioid alfentanil, the low-efficacy opioid nalbuphine, and cocaine using a PR schedule of i.v. drug injection in rhesus monkeys in which the response requirement increased during the experimental session and the initial response requirement (IRR) was varied. Analyses based on either consumer demand or labor supply models of behavioral economics revealed that the relative reinforcing effectiveness of cocaine and alfentanil was greater than that of nalbuphine. These results suggest that PR schedules with varying IRRs can provide meaningful estimates of the relative reinforcing effectiveness of abused drugs.

Alfentanil↗

The influence of exchange delays on cigarette versus money choice: a laboratory analog of voucher-based reinforcement therapy.

Contingency-management interventions that provide reinforcement in the form of exchangeable vouchers, contingent on drug abstinence, are among the most effective substance abuse treatment strategies available. Factors known to contribute to the efficacy of these interventions include voucher magnitude and the schedule with which vouchers are made available. Another potential factor may be the delay between earning a voucher and exchanging it for a desired good or service. The authors adapted a laboratory analog of a voucher program to examine the effects of immediacy of reinforcement and its interaction with reinforcer magnitude. Abstinent cigarette smokers made repeated choices between puffs on a cigarette and points worth a variety of monetary values (10 cents-2 dollars). The time at which these points could be exchanged for money varied from the end of the session to 1 or 3 weeks. Results indicated that longer exchange delays and tower magnitude reinforcers increased the number of choices for drug.

Adult↗

Contingency management treatments: Reinforcing abstinence versus adherence with goal-related activities.

Contingency management (CM) interventions usually reinforce submission of drug-negative specimens, but they can also reinforce adherence with goal-related activities. This study compared the efficacy of the 2 approaches. Substance-abusing outpatients (N = 131) were randomly assigned to 1 of 3 12-week treatments: standard treatment (ST), ST with CM for submitting negative urine toxicology screens, or ST with CM for completing goal-related activities. CM patients remained in treatment longer and achieved more abstinence than ST patients, but the CM condition that reinforced submission of negative samples resulted in better outcomes than the CM condition that reinforced goal-related activities. Abstinence at 6- and 9-month follow-ups did not differ by group, but longest duration of abstinence achieved during treatment was associated with abstinence posttreatment.

Adult↗

Reinforcement in applied settings: figuring out ahead of time what will work.

This article reviews the practical value of conceptual attempts to specify the circumstances of reinforcement ahead of time. Improvements are traced from the transituational-reinforcer approach of Meehl (1950), through the probability-differential model of Premack (1959, 1965), to the response deprivation and disequilibrium approach (Timberlake, 1980, 1984; Timberlake & Allison, 1974). The application value of each approach is evaluated on the grounds of simplicity, accuracy, and adaptability. The article shows that the disequilibrium approach accounts for and extends current empirically driven techniques of reinforcement control and examines some of its limitations. The disequilibrium approach clarifies how current knowledge can be used to predict more accurately the circumstances of reinforcement and invites the collaboration of applied and basic research in its further development.

Behavior Therapy↗