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PubMed2006

Response inhibition during Differential Reinforcement of Low Rates (DRL) schedules may be sensitive to low-level polychlorinated biphenyl, methylmercury, and lead exposure in children.

BACKGROUND: Animal studies have shown that exposure to common, low-level environmental contaminants [e.g., polychlorinated biphenyls (PCBs), lead] causes excessive and inappropriate responding on intermittent reinforcement schedules. The Differential Reinforcement of Low Rates task (DRL) has been shown to be especially sensitive to low-level PCB exposure in monkeys. OBJECTIVES: We investigated the relationships between prenatal PCB and postnatal Pb exposure performance on a DRL schedule in children. We predicted that a) prenatal PCB exposure would reduce interresponse times (IRTs) and reinforcements earned, and b) postnatal Pb exposure would reduce IRTs and reinforcements earned. METHODS: We tested 167 children on a DRL20 (20 sec) reinforcement schedule, and recorded IRTs and the number of reinforced responses across the session. We measured prenatal PCB exposure (cord blood), methylmercury (MeHg) (maternal hair), and postnatal Pb exposure (venous blood), and > 50 potentially confounding variables. RESULTS: Results indicated impaired performance in children exposed to PCBs, MeHg, and Pb. Children prenatally exposed to PCBs responded excessively, with significantly lower IRTs and fewer reinforcers earned across the session. In addition, exposure to either MeHg or Pb predicted statistically significant impairments of a similar magnitude to those for PCBs, and the associated impairments of all three contaminants (PCB, MeHg, and Pb) were statistically independent of one another. CONCLUSIONS: These results, taken with animal literature, argue the high sensitivity of DRL performance to low-level PCB, MeHg, and Pb exposure. Future research should employ behavioral tasks in children, such as DRL, that have been demonstrably sensitive to low-level PCB, MeHg, and Pb exposure in animals.

Analysis of Variance↗
PubMed2001

Choices between positive and negative reinforcement during treatment for escape-maintained behavior.

Positive reinforcement was more effective than negative reinforcement in promoting compliance and reducing escape-maintained problem behavior for a child with autism. Escape extinction was then added while the child was given a choice between positive or negative reinforcement for compliance and the reinforcement schedule was thinned. When the reinforcement requirement reached 10 consecutive tasks, the treatment effects became inconsistent and reinforcer selection shifted from a strong preference for positive reinforcement to an unstable selection pattern.

Autistic Disorder↗
PubMed1963

The role of temporal discriminations in the reinforcement of Sidman avoidance behavior.

Animals learn to avoid with the Sidman procedure even though the avoidance response is not followed by the termination of any warning stimulus in the environment. What reinforces this response? The accepted explanation has been that the avoidance response is reinforced when it terminates other behavior that has become aversive by pairing with shock. However, the reinforcement may also be derived from the temporal discriminations that develop with Sidman avoidance. These and other temporal discriminations show that the animal has available some events that vary with the postresponse time. The shock will closely follow the temporal stimuli at long postresponse times and would be expected to make them aversive. The stimuli at short postresponse times would have a relatively low aversiveness due to their more remote relation to shock. Since the avoidance response changes a long postresponse time to a short one, that response would be followed by a decrease in aversiveness which would reinforce it. When sharp temporal discriminations are present, reinforcement from the decrease in aversiveness of temporal stimuli probably plays a dominant role in maintaining the avoidance response. This formulation fits the available data and has adequate answers for the objections that have been raised to earlier conceptions of the role temporal discriminations might play in Sidman avoidance. Although under some conditions the reinforcement in Sidman avoidance seems to be primarily due to the decrease in aversiveness of temporal stimuli, under other conditions there probably is reinforcement from the termination of conditioned aversive responses.

Animals↗
PubMed1964

DIFFERENTIAL REINFORCEMENT OF VOCAL DURATION.

The effects of differential reinforcement of vocal duration were examined in a series of experiments in which each of 28 subjects (Ss) emitted a vowel whenever a light was flashed. In the first phase of each experiment, a penny was dispensed after each of 20 responses. In the second and subsequent phases, only those responses whose durations exceeded a criterion were reinforced; when 10 successive reinforcements were presented, one phase was terminated and the next begun. The criterion for reinforcement in each phase was determined by a different schedule in each of six experiments; it ranged from 80 to 120 per cent of the mean duration of the 10 terminal responses in the prior phase. Differential reinforcement effected a large and systematic change in the duration of vocal responses as long as the responses selected for reinforcement had a sufficiently high probability of occurrence. This requirement was formulated as the difference between the criterion duration and the mean duration of the terminal responses in the prior phase, divided by their standard deviation. This statistic, named the shaping index, was correlated with the number of responses emitted before each phase was terminated. It was found to be large whenever the shaping process failed. Many Ss failed to tact the reinforcement contingency despite marked changes in their vocal behavior and extensive probing by a questionnaire, administered at the end of each session.

Humans↗
PubMed1972

Characteristics and response-displacement effects of shock-generated responding during negative reinforcement procedures: pre-shock responding and post-shock aggressive responding.

Bar-pressing (Experiment I) or key-pressing (Experiments II and III) responses of monkeys were reinforced according to a fixed-interval schedule of negative reinforcement: the first response after a fixed interval of time terminated regularly spaced shocks for a fixed time designated as the reinforcement period. During extinction, shocks continued during the reinforcement period. That there were two types of responding generated by shock alone was indicated by (1) the level of responding maintained during extinction relative to conditions without shock, (2) the stability of two between-shock response patterns across reinforcement and extinction conditions, and (3) the development of these two between-shock patterns without a history of reinforcement. Subjects developed either a pre-shock or a post-shock response pattern when only the bar was available. However, when both a bite tube, an operandum requiring an aggressive topography, and a recessed key, an operandum that did not require an aggressive topography, were provided, the post-shock pattern was observed in tube biting and the pre-shock pattern was observed in key pressing. Removal of the bite tube produced post-shock key responding similar to that observed when only the bar was available. The displacement of post-shock, aggression-motivated responding confirmed the confounding effect of shock-generated responding in negative reinforcement procedures, and suggests that the use of concurrent response alternatives would reduce such confounding.

Aggression↗
PubMed2005

Does sensitivity to magnitude depend on the temporal distribution of reinforcement?

Our research addressed the question of whether sensitivity to relative reinforcer magnitude in concurrent chains depends on the distribution of reinforcer delays when the terminal-link schedules are equal. In Experiment 1, 12 pigeons responded in a two-component procedure. In both components, the initial links were concurrent variable-interval 40-s variable-interval 40-s, and the terminal links were both 20-s interval schedules in which responses were reinforced by either 4-s of grain in one, or 2-s of grain in the other. The only difference between the components was whether the terminal-link schedules were fixed interval or variable intervals. For all subjects, the relative rate of responding in the initial links for the terminal link that produced the 4-s reinforcer was greater when the terminal links were fixed-interval schedules than when they were variable-interval schedules. This result is contrary to the prediction of Grace's (1994) contextual choice model, but is consistent with both Mazur's (2001) hyperbolic value-added model and Killeen's (1985) incentive theory. In Experiment 2, 4 pigeons responded in a concurrent-chains procedure in which 4-s or 2-s reinforcers were provided independently of responding according to equal fixed-time or mixed-time schedules. Preference for the 4-s reinforcer increased as the variability of the intervals comprising the mixed-time schedules was decreased. Generalized-matching sensitivity of initial-link response allocation to relative reinforcer magnitude was proportional to the geometric mean of the terminal-link delays.

Animals↗
PubMed2005

Within-subject testing of the signaled-reinforcement effect on operant responding as measured by response rate and resistance to change.

Response rates under random-interval schedules are lower when a brief (500 ms) signal accompanies reinforcement than when there is no signal. The present study examined this signaled-reinforcement effect and its relation to resistance to change. In Experiment 1, rats responded on a multiple random-interval 60-s random-interval 60-s schedule, with signaled reinforcement in only one component. Response resistance to alternative reinforcement, prefeeding, and extinction was compared between these components. Lower response rates, and greater resistance to change, occurred in the component with the reinforcement signal. In Experiment 2, response rates and resistance to change were compared after training on a multiple random-interval 60-s random-interval 60-s schedule in which reinforcer delivery was unsignaled in one component and a response-produced uncorrelated stimulus was presented in the other component. Higher response rates and greater resistance to change occurred with the uncorrelated stimulus. These results highlight the significance of considering the effects of an uncorrelated signal when used as a control condition, and challenge accounts of resistance to change that depend solely on reinforcer rate.

Animals↗
PubMed1985

Behavioral screen for antidepressants: the effects of drugs and electroconvulsive shock on performance under a differential-reinforcement-of-low-rate schedule.

Those antidepressant drugs that are in wide clinical use decrease response rate and increase reinforcement rate when administered to rats performing on a differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule. Drugs that are not antidepressants do not have this effect. In this experiment, the following were examined for their effects on a DRL 72-s schedule: trazodone, zimelidine, fluoxetine, and bupropion (atypical antidepressants); electroconvulsive shock (ECS, which is an effective treatment for depression); and haloperidol and clozapine (antipsychotic drugs). Trazodone (3.12-25.00 mg/kg), fluoxetine (10-20 mg/kg), and ECS decreased response rate and increased reinforcement rate. Zimelidine (20 mg/kg) increased reinforcement rate and nonsignificantly decreased response rate. At doses between 2.5 and 40 mg/kg, bupropion had no effect on reinforcement rate or response rate, but at 60 mg/kg response rate was increased and reinforcement rate was nonsignificantly decreased. At the higher dose, the effects of bupropion resemble those of a psychomotor stimulant. Haloperidol (0.04 mg/kg) and clozapine (2.5-10.0 mg/kg) decreased response rate and reinforcement rate. These results suggest that the DRL 72-s schedule may be useful for testing the antidepressant potential of new drugs.

Animals↗
PubMed1981

Control of alcohol tolerance by reinforcement in nonalcoholics.

The development of tolerance to alcohol was examined in two experiments with nonalcoholic drinkers. In both experiments, male undergraduates received pretraining on a pursuit rotor task and were then randomly assigned to either alcohol or placebo conditions. In the first experiment, monetary and performance feedback reinforcement for pursuit rotor performance were provided to both groups over four drinking sessions. In the second experiment, two final drinking sessions were added where no reinforcement was provided to either the alcohol or placebo subjects, and an additional alcohol group received no reinforcement throughout the six drinking sessions. Tolerance to the impairing effects of alcohol on pursuit rotor performance developed only for the reinforced alcohol subjects; withdrawal of reinforcement from tolerant subjects resulted in a return of impaired performance, i.e. tolerance was extinguished. Impairment remained consistently high in the non-reinforced alcohol subjects throughout all six drinking sessions. The results provide support for the learning hypothesis of behavioural tolerance by demonstrating that its acquisition and extinction may be controlled by reinforcement.

Adult↗
PubMed1995

Conditioned reinforcing effects of capsules associated with high versus low monetary payoff.

The ability of a placebo drug capsule to serve as a conditioned reinforcer as a function of being paired with money reinforcement was evaluated. Volunteers were administered two differently colored capsules that presumably contained two different drugs. Although the volunteers were told they might contain a stimulant, sedative, or placebo, both capsules contained only a placebo. During sessions, volunteers participated in performance tasks. The tasks were programmed so that following one capsule, the amount of money obtained contingent upon responding was greater (high frequency of reinforcement) than following the other capsule (low frequency of reinforcement). During experiment 1, participants were exposed twice each to the two reinforcement conditions (sampling). During these choice sessions, 9 of 12 participants chose the capsule associated with the high frequency of reinforcement 2 or 3 times. Experiment 2 was designed to explore further whether the differential mood effects observed during sampling sessions could be conditioned. Although this could not be demonstrated, the self-administration results demonstrating the control of choice behavior even in the absence of pharmacological effects suggest that drugs may function as conditioned reinforcers. This finding has implications for broadening our understanding of the determinants of initiation and continued drug use.

Adult↗
PubMed2002

Relation between discriminative and reinforcing effects of midazolam, pentobarbital, chlordiazepoxide, zolpidem, and imidazenil in baboons.

RATIONALE: If a psychoactive drug shares discriminative effects with one that maintains self-administration, it is often inferred that the test drug is likely to be self-administered and to have abuse liability. This presumed predictive relationship has not been studied directly, however. OBJECTIVE: To determine at the level of the individual subject (1) whether a novel drug dose that shares discriminative effects with a reinforcing drug dose also will serve as a reinforcer, and (2) whether the results of generalization tests for drugs pharmacologically similar to the training drug predict whether the test drugs will or will not be self-administered. METHODS: Baboons were trained to discriminate midazolam (0.32 mg/kg, IV) from saline and also under a schedule of IV drug reinforcement. At the beginning of a period of self-administration, the first self-injection was followed 10 min later by a drug discrimination test session. The baboon then had the opportunity to self-administer the same dose 24 h/day (3-h timeout after each injection). A second drug discrimination test followed the last self-injection of the condition. RESULTS: Zolpidem and imidazenil shared discriminative effects with midazolam. Zolpidem was reinforcing in all baboons, but imidazenil was not. Chlordiazepoxide partially shared discriminative effects with midazolam, and the rate of self-administration was low. Pentobarbital did not share discriminative effects with midazolam, but was reinforcing. For all drugs, some doses did not share discriminative effects with midazolam but were reinforcing. Generalization gradients from tests after the last self-injection were similar to those after the first self-injection. CONCLUSIONS: The discriminative effect of a drug in relation to a training drug of the same pharmacological class is not isomorphic with its reinforcing effectiveness.

Animals↗
PubMed2002

Sex differences in the subjective and reinforcing effects of cigarette nicotine dose.

RATIONALE: Some research with novel nicotine delivery methods suggests that nicotine itself may be less reinforcing in women than in men. However, sex differences in the reinforcing effects of nicotine dose via cigarette smoking have received little attention. OBJECTIVES: Sex differences in the subjective and reinforcing effects of smoking were examined as a function of two cigarette nicotine "dose" levels (moderate - subjects' preferred brand, > or = 0.7 mg yield; low - Carlton "ultra-light", 0.1 mg yield). METHODS: Male and female smokers ( n = 30) participated in three sessions, the first two involving independent assessment (only one brand available), and the third involving concurrent assessment (both brands available), of subjective ratings (e.g. "liking") and reinforcement for the two cigarette brands. Subjects were blind to the brand of each cigarette, and subjects abstained overnight prior to each session. Reinforcement was determined by responses on a computer task to earn single puffs on the designated cigarette. RESULTS: Subjective ratings differed between the low versus moderate cigarette nicotine dose under both independent and concurrent assessment conditions, as expected. Notably, this dose difference was smaller in women than in men (i.e. significant sex by dose interactions). The dose effect on smoke reinforcement also was smaller in women than men, but only under the independent and not concurrent assessment condition. CONCLUSIONS: These results indicate that cigarette nicotine dose is a less important influence on the subjective and, under some conditions, reinforcing effects of smoking in women than in men.

Adult↗
PubMed2006

Effects of memantine, haloperidol, and cocaine on primary and conditioned reinforcement associated with cocaine in rhesus monkeys.

RATIONALE: The N-methyl-D-aspartate (NMDA) receptor has been implicated in mediating the reinforcing effects of abused drugs. Some reports indicate the uncompetitive NMDA antagonist, memantine, modulates the conditioned and unconditioned effects of stimulants in rats. OBJECTIVE: The objective of this study was to evaluate the effects of memantine on the primary and conditioned reinforcing effects of cocaine in the rhesus monkey. METHODS: Rhesus monkeys were trained to press levers reinforced with either cocaine-associated stimuli (brief stimuli, BS) or 30-microg/kg cocaine infusion during daily, 75-min experimental sessions in which the reinforcers were independently available in separate components according to identical progressive ratio (PR) schedules. Memantine (0.3-10 mg/kg), and as comparators, haloperidol (0.001-0.1 mg/kg) and cocaine (0.01-1 mg/kg), were administered 5 min before experimental sessions. RESULTS: Memantine (0.3-3 mg/kg) produced decreases in responding maintained by BS presentations at some doses which failed to affect cocaine self-administration when measured during equivalent periods early in the experimental session. Memantine (3 mg/kg) increased cocaine self-administration, however, later in the session. A low dose of haloperidol (0.001 mg/kg) increased the number of BS presentations, whereas higher doses decreased their number. Cocaine self-administration was not significantly affected by haloperidol until a behaviorally suppressant dose (0.1 mg/kg) was administered. Pretreatment with high doses of cocaine (0.3 and 1 mg/kg) decreased responding maintained by both reinforcers. CONCLUSION: These results suggest that while memantine may attenuate the conditioned reinforcing effects of cocaine-associated stimuli, it may also occasion increase levels of cocaine self-administration. These findings support the hypothesis that the NMDA receptor can play a role in modulating the conditioned and primary reinforcing effects of cocaine.

Animals↗
PubMed2006

Association of OPRM1 A118G variant with the relative reinforcing value of nicotine.

RATIONALE: The endogenous opioid system has been implicated in substance abuse and response to pharmacotherapies for nicotine and alcohol addiction. We examined (1) the association of the functional OPRM1 A118G variant with the relative reinforcing value of nicotine and (2) the main and interacting effects of the mu-opioid receptor antagonist naltrexone on nicotine reinforcement. METHODS: In a within-subject, double-blind human laboratory study, 30 smokers of each OPRM1 genotype (A/A vs. A/G or G/G) participated in two experimental sessions following 4 days of orally administered naltrexone 50 mg or placebo. Participants completed a validated assessment of the relative reinforcing value of nicotine. This cigarette choice paradigm assesses self-administration of 0.6 mg nicotine vs. 0.05 mg (denicotinized) cigarettes after a brief period of nicotine abstinence. RESULTS: The relative reinforcing value of nicotine (number of nicotine cigarette puffs) was predicted by a significant OPRM1 by gender interaction. Among women, the low-activity G allele (A/G and G/G) was associated with a reduced reinforcing value of nicotine; among male smokers, there was no association with genotype. Smokers carrying a G allele were also significantly less likely to differentiate the nicotine vs. denicotinized cigarettes by subjective ratings of satisfaction and strength. No evidence for an effect of naltrexone on nicotine reinforcement was found in the overall sample or in the genotype or gender subgroups. CONCLUSIONS: This study provides initial evidence for an association of the OPRM1 A118G variant with nicotine reinforcement in women.

Adaptation, Psychological↗
PubMed2006

Reinforcement schedule effects in rats trained to discriminate 3,4-methylenedioxymethamphetamine (MDMA) or cocaine.

RATIONALE: Relatively few studies have compared the discriminative stimulus effects of 3,4-methylenedioxymethamphetamine (MDMA) and cocaine, and findings from different laboratories are somewhat inconsistent. One possible reason for discrepant results may be the use of different reinforcement schedules during discrimination training. OBJECTIVE: The present study compared fixed ratio (FR) 20 and variable interval (VI) 15-s reinforcement schedules to determine their influence on discrimination acquisition, response rates, frequency of reinforcements, and stimulus generalization in rats trained to discriminate cocaine or MDMA. MATERIALS AND METHODS: Thirty-two male Sprague-Dawley rats were trained to discriminate cocaine (10 mg/kg; n=16) or MDMA (1.5 mg/kg; n=16) from saline under either a FR 20 or a VI 15-s schedule of food reinforcement. Stimulus generalization tests were conducted with a range of doses of cocaine, MDMA, d-amphetamine, and lysergic acid diethylamide in all four training groups. RESULTS: The FR 20 schedule facilitated more rapid discrimination acquisition compared to the VI 15-s schedule and established differential response rates and frequency of reinforcement under drug and vehicle conditions. However, reinforcement schedule had little influence on stimulus generalization between MDMA and cocaine. Cocaine produced partial substitution for MDMA in both training groups (FR 20, 51%; VI 15-s, 58%). Likewise, MDMA produced only partial substitution for cocaine in both training groups (FR 20, 40%; VI 15-s, 72%). CONCLUSIONS: The present findings suggest that the number of sessions required to establish discriminative stimulus control varies with different reinforcement schedules. Nevertheless, training schedules alone do not appear to have significant effects on stimulus generalization between MDMA and cocaine.

Animals↗
PubMed2000

Self-administration of remifentanil, an ultra-short acting opioid, under continuous and progressive-ratio schedules of reinforcement in rats.

RATIONALE: Remifentanil is a mu-opioid agonist with an exceptionally short duration of action. Evaluating remifentanil's effects within the self-administration model of drug abuse may provide insight into the relationship between a drug's duration of action and its effectiveness as a reinforcer. OBJECTIVES: This study was conducted to establish a dose-effect function for intravenous remifentanil self-administration in rats and to assess the drug's ability to maintain responding under intermittent schedules of reinforcement. METHODS: Inter-infusion intervals were recorded under two continuous-reinforcement schedules of remifentanil self-administration. In the fixed-dose schedule, the unit dose (0.25-32 micrograms/kg) was held constant within sessions but varied across sessions. In the variable-dose schedule, four different doses were self-administered in random order within each session. For comparison, heroin (6.25-125 micrograms/kg) was studied with the variable-dose schedule. Remifentanil and heroin were also compared under a progressive-ratio schedule of reinforcement in which the response requirements increased exponentially with each successive infusion until responding ceased within each session. RESULTS: Under the continuous-reinforcement schedules, inter-infusion intervals for both drugs increased monotonically as a function of dose, with the remifentanil curve being considerably flatter. Under the progressive-ratio schedule, breaking points varied as an inverted-U shaped function, and the highest breaking points maintained by remifentanil and heroin were similar. At the doses that maintained the highest breaking points under the progressive-ratio schedule, post-infusion pauses under the continuous-reinforcement schedule were about three times shorter with remifentanil than with heroin. CONCLUSIONS: Although rates of self-administration are clearly influenced by a drug's duration of action, the ability to maintain responding under intermittent schedules of reinforcement may be independent of duration of action.

Analgesics, Opioid↗
PubMed1998

Choice maintained by cocaine or food in monkeys: effects of varying probability of reinforcement.

Several theoretical models of choice, including matching, maximizing and probability matching, have evolved from the experimental analysis of behavior. However, these models are based largely on results of studies involving non-drug reinforcers. The extent to which the choice to self-administer a drug of abuse conforms to these models is largely unknown. The present study was designed to examine the effects of varying probability of reinforcement of two options on choice by rhesus monkeys maintained under a discrete-trials choice procedure. One group of monkeys (n=5) was prepared with chronic indwelling venous catheters and responding was maintained by i.v. injections of cocaine (0.05 or 0.2 mg/kg per injection). In a second group, behavioral conditions were identical, except that responding was maintained by the delivery of food pellets. Two choice options were available to each group. Each option was maintained by the identical dose of cocaine or amount of food, but with varying probabilities of delivery. The percentage of trials on which monkeys chose option 1 increased with its probability of reinforcement for cocaine (0.05 or 0.2 mg/kg per injection) and this effect did not change with dose of cocaine. When probabilities of reinforcement for option 1/option 2 were 0.75/0.25, choice was exclusive for the higher probability option. Results were identical when behavior was maintained by food. The present experiment supports the conclusion that exclusive choice of the alternative with the higher probability of reinforcement can be extended to cocaine as a reinforcer. The present results also extend the known conditions under which drug-maintained responding is similar to food-maintained responding to situations involving options with different probabilities of reinforcement, i.e., probability choice. Probability matching was not observed, arguing that this model does not predict drug or food choice.

Animals↗
PubMed1999

Naltrexone pretreatment decreases the reinforcing effectiveness of ethanol and saccharin but not PCP or food under concurrent progressive-ratio schedules in rhesus monkeys.

The purpose of this experiment was to determine whether attenuation of ethanol consumption by naltrexone is the result of selective changes in the reinforcing effectiveness of drug and non-drug reinforcers. A range of naltrexone doses (0.1-1.0 mg/kg) was administered for 5 days, and the effects on the reinforcing effects of orally delivered 8% (w/v) ethanol, 0.25 mg/ml phencyclidine (PCP), 0.03% (w/v) saccharin and food were studied in eight rhesus monkeys. Food and liquids were available under independent and concurrent progressive-ratio (PR) schedules (ratio range 8-4096) during daily 3-h sessions. Ethanol-maintained responding was attenuated by 0.3 and 1.0 mg/kg doses of naltrexone, while saccharin-maintained responding was decreased at the 1.0 mg/kg dose. Furthermore, there was a significant linear trend that consumption of available ethanol and saccharin was attenuated dose-dependently by naltrexone. Following 5 days of naltrexone pretreatment, ethanol- and saccharin-maintained responding immediately returned to or exceeded baseline levels. Food- and PCP-maintained responding and intake were not significantly affected by any of the naltrexone doses examined. The decreased break point (BP) values for ethanol and saccharin suggest that their reinforcing effects are mediated through opioid reinforcement mechanisms. The lack of naltrexone attenuation of PCP- and food-maintained responding suggests that these reinforcers: 1) are not sensitive to naltrexone antagonism at the doses examined, 2) are mediated by non-opioid reinforcement mechanisms, and/or 3) have less intrinsic palatability.

Animals↗