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Learning improvement of appetitively or aversively reinforced light-dark discrimination and reversal four weeks after electrical stimulation of the lateral hypothalamus of the rat.

The experiments reported here point out the effect of electrical stimulation of the lateral hypothalamus on the acquisition and reversal of a simultaneous light-dark discrimination performed 4 weeks later. The stimulation was applied on 15-day-old rats. There were two control groups, implanted but not stimulated and non-implanted rats. In the first experiment, the light-dark discrimination task was food-reinforced. As already reported in the case of an appetitively reinforced operant task, stimulation of the lateral hypothalamus induced an important improvement of performance in discrimination and reversal. This improvement was already apparent at the beginning of acquisition. In the reversal task the mean response latency of stimulated rats was greater than tht of control animals. In the second experiment with naive rats we used the same discrimination but the task was aversively reinforced by an electric foot-shock. In spite of the different type of reinforcement used, the stimulated rats performed better than the control rats in the three behavioral situations studied: avoidance, discrimination and reversal. As in the first experiment the improvement appeared at the onset of acquisition in the three situations. Thus the long-term effect of lateral hypothalamic stimulation does not depend on the type of reinforcement, nor the behavioral task. These results are briefly discussed.

Animals↗

Dopamine D2/D3 receptors modulate cocaine's reinforcing and discriminative stimulus effects in rhesus monkeys.

Numerous studies have suggested that dopamine (DA) D2 and D3 receptors are involved in the behavioral effects of cocaine. The present experiments evaluated the reinforcing and cocaine-like discriminative stimulus effects of several D2/D3 agonists in rhesus monkeys. In the first experiment, animals (n = 4) were trained to self-administer 0.03 mg/kg/inj cocaine under a fixed-interval (FI) 5-min schedule. When substituted for cocaine, the D2/D3 agonist quinpirole (0.003-0.03 mg/kg/inj) functioned as a reinforcer in all monkeys. In two cocaine-naive monkeys trained to respond under an FI 3-min schedule of food presentation, quinpirole maintained low rates of responding in one subject, while at the highest dose (0.03 mg/kg/inj) it functioned as a reinforcer in the second monkey. In this animal, increased activity was observed at this dose, which may have contributed to the overall rate of responding. In the second experiment, monkeys (n = 4) were trained to discriminate cocaine from saline using a two-lever, food-reinforced, drug discrimination procedure. The D2/D3 agonists quinpirole, (+/-)-7-OH-DPAT, and R-( + )-7-OH-DPAT fully substituted for cocaine. However, the time-course of substitution differed between quinpirole, which substituted for cocaine 10 min after administration, and (+/-)- and R-(+)-7-OH-DPAT, which required 60-min pretreatments. The behavioral potencies, as determined from ED50, values, correlated with previously reported in vitro binding affinity and functional activity at the D3 receptor [R-(+ )-7-OH-DPAT > (+/-)-7-OH-DPAT > quinpirole]. These results further indicate that direct-acting D2/D3 agonists can function as reinforcers and produce cocaine-like discriminative stimulus effects, and support the idea that D3 receptors should continue to be a valuable target for future behavioral studies evaluating cocaine's mechanisms of action.

Analysis of Variance↗

Opioid reinforcement in heroin-dependent volunteers during outpatient buprenorphine maintenance.

This study examined the reinforcing effects of hydromorphone (HYD) (0, 4, 8, and 16 mg/70 kg i.m.) in heroin-dependent outpatient volunteers maintained on buprenorphine (BUP) at doses of 2, 4, and 8 mg, each for 2 weeks. Following a week of maintenance at each dose, volunteers received injections of one of the four HYD doses under double-blind conditions. Eight volunteers (abstainers) were heroin-free during HYD test weeks, whereas six volunteers remained heroin-positive (nonabstainers). Among abstainers, HYD had minimal reinforcing value, whereas in nonabstainers there were marked dose-related increases in HYD reinforcing value, which were not attenuated by increasing doses of BUP. A similar pattern was found for HYD subjective agonist effects. Heroin craving among nonabstainers was significantly higher compared with abstainers, and was reduced in a dose-related manner by HYD. Although BUP and HYD produced dose-related miosis, abstinence status had no differential effect. In summary, BUP effects on opioid reinforcement were consistent from outpatient setting (heroin abstinence) to laboratory setting (decreased HYD reinforcement), supporting the validity of this laboratory model.

Adult↗

Local analysis of behaviour in the adjusting-delay task for assessing choice of delayed reinforcement.

The adjusting-delay task introduced by Mazur (Quantitative analyses of behavior: V. The effect of delay and of intervening events on reinforcement value, 1987, pp. 55-73) has been widely used to study choice of delayed reinforcers. This paradigm involves repeated choice between one reinforcer delivered after a fixed delay and another, typically larger, reinforcer delivered after a variable delay; the variable delay is adjusted depending on the subject's choice until an equilibrium point is reached at which the subject is indifferent between the two alternatives. Rats were trained on a version of this task and their behaviour was examined to determine the nature of their sensitivity to the adjusting delay; these analyses included the use of a cross-correlational technique. No clear evidence of sensitivity to the adjusting delay was found. A number of decision rules, some sensitive to the adjusting delay and some not, were simulated and it was observed that some effects usually supposed to be a consequence of delay sensitivity could be generated by delay-independent processes, such as a consistent, unchanging relative preference between the alternatives. Consequently, the use of explicit analysis of delay sensitivity is advocated in future research on delayed reinforcement.

Animals↗

Adjusting to changes in the time of reinforcement: peak-interval transitions in rats.

Thirty rats received training on a peak-interval procedure, where a baseline with a 20-s time of reinforcement was interspersed among cyclic transitions to other reinforcement time values (10, 20, 30, or 40 s), each of which was either in force for only a single session or for 3 sessions. Peak times were close to the time of reinforcement on the 20-s baseline and tracked the new reinforcement times both closely (but not exactly) and very rapidly. Peak time during transitions was affected by the criterion value in force on the previous session, exhibiting a proactive interference effect. Analysis of individual peak times during a session showed that transitions from lower to higher reinforcement time values were usually characterized by abrupt jumps in peak time, whereas descending transitions were mostly smooth but rapid.

Animals↗

Associative changes in elements and compounds when the other is reinforced.

Four experiments investigated the symmetry of associative changes in stimulus compounds and elements in a Pavlovian conditioned magazine-approach situation with rats. Experiment 1 used multiple groups to examine the associative changes in a conditioned element (A) as a result of its subsequent reinforcement in compound with a neutral X. These were compared with the changes in an AX compound when one of its elements (A) was subsequently reinforced alone. Although reinforcing A enhanced responding to the AX compound, compared with a control compound, reinforcing AX failed to enhance responding to A, compared with a control element. Experiments 2 and 3 made similar comparisons in a fully within-subject design, finding greater changes in a previously trained AX compound when A was subsequently conditioned than in a B element when BY was subsequently conditioned. Experiment 4 found associative decrements in A when it was reinforced in the presence of a moderately conditioned X. The results observed in each of these experiments are more consistent with an elemental model of conditioning than with a recently proposed configural model.

Acoustic Stimulation↗

Allegations of wrongdoing: the effects of reinforcement on children's mundane and fantastic claims.

S. Garven, J. M. Wood, R. S. Malpass, and J. S. Shaw (1998) found that the interviewing techniques used in the McMartin Preschool case can induce preschool children to make false allegations of wrong doing against a classroom visitor. In this study, 2 specific components of the McMartin interviews, reinforcement and cowitness information, were examined more closely in interviews of 120 children, ages 5 to 7 years. Children who received reinforcement made 35% false allegations against a classroom visitor, compared with 12% made by controls. When questioned about "fantastic" events (e.g., being taken from school in a helicopter), children receiving reinforcement made 52% false allegations, compared with 5% made by controls. In a second interview, children repeated the allegations even when reinforcement had been discontinued. The findings indicate that reinforcement can swiftly induce children to make persistent false allegations of wrong doing.

Child↗

A randomized trial of long-term reinforcement of cocaine abstinence in methadone-maintained patients who inject drugs.

This study determined whether long-term abstinence reinforcement could maintain cocaine abstinence throughout a year long period. Patients who injected drugs and used cocaine during methadone treatment (n = 78) were randomly assigned to 1 of 2 abstinence-reinforcement groups or to a usual care control group. Participants in the 2 abstinence-reinforcement groups could earn take-home methadone doses for providing opiate- and cocaine-free urine samples; participants in 1 of those groups also could earn 5,800 US dollars in vouchers for providing cocaine-free urine samples over 52 weeks. Both abstinence-reinforcement interventions increased cocaine abstinence, but the addition of the voucher intervention resulted in the largest and most sustained abstinence. Therefore, voucher-based reinforcement of cocaine abstinence in methadone patients can be a highly effective maintenance intervention.

Adolescent↗

Acquisition with partial and continuous reinforcement in rat magazine approach.

Partial reinforcement, compared with continuous reinforcement, is widely considered detrimental to Pavlovian conditioned responding. However, time-accumulation models predict an invariance in acquisition when learning is assessed as a function of number of reinforcements, not trials, and intertrial interval is held constant. Three experiments examined this prediction in a rat magazine-approach procedure. All experiments showed superior responding with continuous reinforcement. Experiments 1 and 3 used common tests in between- and within-subject designs, respectively. Experiment 2 showed the same pattern in a discrimination. Earlier results are reanalyzed informally and in a meta-analysis. Contrary to previous summaries of the literature, evidence points to superior conditioned responding with continuous reinforcement in a number of procedures. Results are generally consistent with traditional associative models of learning.

Animals↗

Sex differences in social reinstatement motivation of the domestic chick (Gallus gallus) revealed by runway tests with social and nonsocial reinforcement.

Male and female chicks (Gallus gallus) were trained at 4 days old to run along a corridor to reach a goal box that contained either cagemates (social reinforcement) or food (nonsocial reinforcement). Females ran faster when social reinforcement was used, whereas males ran faster with nonsocial reinforcement. When social reinforcement was used with a V-shaped runway, in which chicks had to proceed toward the goal object in an indirect fashion, sex differences were reversed. The results may be due to stronger social reinstatement tendencies in females than in males: Higher levels of social motivation facilitate behavioral performance when the task is easy (straight runway) and inhibit it when the task is difficult (V-shaped runway).

Animals↗

Effects of sex steroids on maternal motivation in the common marmoset (Callithrix jacchus): development and application of an operant system with maternal reinforcement.

We developed an operant paradigm for measuring effects of reproductive steroids on maternal motivation in common marmosets (Callithrix jacchus). Conditioned response regulated females' exposure to maternal reinforcement. Nulliparous females (n = 15) with experience with infants in social groups were subjects. The paradigm was validated by examining (a) effects of reinforcing stimuli on affective behavior in a nonoperant paradigm, (b) responsiveness of operant performance to changes in reinforcing stimuli and reinforcement schedule, (c) changes in operant responding due to omission of reinforcement, and (d) relation between operant responding and species-typical maternal behavior. In pregnant females, (n = 4), frequency of bar pressing and estradiol:progesterone ratio were maximal just before birth. Nonpregnant females (n = 3) treated with progesterone and estradiol to mimic late-pregnancy steroid profiles showed increased operant maternal behavior.

Acoustic Stimulation↗

The role of perirhinal cortex in visual discrimination learning for visual secondary reinforcement in rats.

Perirhinal cortex in monkeys has been thought to be involved in visual associative learning. The authors examined rats' ability to make associations between visual stimuli in a visual secondary reinforcement task. Rats learned 2-choice visual discriminations for secondary visual reinforcement. They showed significant learning of discriminations before any primary reinforcement. Following bilateral perirhinal cortex lesions, rats continued to learn visual discriminations for visual secondary reinforcement at the same rate as before surgery. Thus, this study does not support a critical role of perirhinal cortex in learning for visual secondary reinforcement. Contrasting this result with other positive results, the authors suggest that the role of perirhinal cortex is in "within-object" associations and that it plays a much lesser role in stimulus-stimulus associations between objects.

Animals↗

Spontaneous recovery and dishabituation of ethanol-reinforced responding in alcohol-preferring rats.

This study examined whether habituation, a decrease in responsiveness to a repeatedly presented stimulus, occurs to ethanol reinforcers in alcohol-preferring (P) rats. Three fundamental properties of habituation were evaluated: generality, spontaneous recovery, and dishabituation. In each experiment, P rats' lever pressing was reinforced by 10% ethanol on a variable-interval 15-s schedule during 50-min sessions. Experiment 1 evaluated the generality of habituation to repeatedly presented stimuli by using ethanol and water reinforcers. Rates of responding were higher for ethanol than they were for water. Additionally, the within-session patterns of responding differed for each reinforcer, suggesting that the pattern of responding was specific to the exact nature of the repeatedly presented reinforcer. Experiment 2 examined spontaneous recovery, an increase in responsiveness to a habituated stimulus when that stimulus is not presented for a time, by separating experimental sessions by 5 min, 2 hr, or 24 hr. Early-session rates of responding during Session 2 were slower than the corresponding rates during Session 1 when sessions were separated by 5 min or 2 hr. Response rates and within-session patterns of responding during Sessions 1 and 2 were similar when sessions were separated by 24 hr. Experiment 3 tested for dishabituation, a restoration of responsiveness following the presentation of an extraneous stimulus, by presenting a tone or a light 24 min and 55 s into the session. Rates of responding temporarily increased after the tone was presented. The results of these experiments support the idea that habituation contributes to the regulation of ethanol consumption.

Alcohol Drinking↗

Disinhibition and spontaneous recovery of response decrements produced by free reinforcement in rats.

Spontaneous recovery and disinhibition were studied in 3 experiments in which, after rats had been trained to bar press on a variable interval schedule of reinforcement, response rates were reduced by the introduction either of extinction or of a response-independent (free) reinforcement schedule. Spontaneous recovery was consistently obtained in extinction, especially when session durations were long. Under free reinforcement conditions there was little sign of spontaneous recovery, even when with high reinforcement rates response reduction was almost as rapid as in extinction. In disinhibition tests the introduction of noise produced increased responding under free reinforcement conditions, but not in extinction. The results are interpreted as demonstrating a dissociation between spontaneous recovery and disinhibition.

Animals↗

The reinforcing properties of alcohol are mediated by GABA(A1) receptors in the ventral pallidum.

It has been hypothesized that alcohol addiction is mediated, at least in part, by specific gamma-aminobutyric acid(A) (GABA(A)) receptors within the ventral pallidum (VP). Among the potential GABA(A) receptor isoforms regulating alcohol-seeking behaviors within the VP, the GABA(A) alpha1 receptor subtype (GABA(A1)) appears pre-eminent. In the present study, we developed beta-carboline-3-carboxylate-t-butyl ester (betaCCt), a mixed agonist-antagonist benzodiazepine (BDZ) site ligand, with binding selectivity at the A1 receptor to explore the functional role of VP(A1) receptors in the euphoric properties of alcohol. The in vivo actions of betaCCt were then determined following microinfusion into the VP, a novel alcohol reward substrate that primarily expresses the A1 receptor. In two selectively bred rodent models of chronic alcohol drinking (HAD-1, P rats), bilateral microinfusion of betaCCt (0.5-40 microg) produced marked reductions in alcohol-reinforced behaviors. Further, VP infusions of betaCCt exhibited both neuroanatomical and reinforcer specificity. Thus, no effects on alcohol-reinforced behaviors were observed following infusion in the nucleus accumbens (NACC)/caudate putamen (CPu), or on response maintained by saccharin. Parenteral-administered betaCCt (1-40 mg/kg) was equally effective and selective in reducing alcohol-reinforced behaviors in P and HAD-1 rats. Additional tests of locomotor activity revealed that betaCCt reversed the locomotor sedation produced by both chlordiazepoxide (10 mg/kg) and EtOH (1.25 g/kg), but was devoid of intrinsic effects when given alone. Studies in recombinant receptors expressed in Xenopus oocytes revealed that betaCCt acted as a low-efficacy partial agonist at alpha3beta3gamma2 and alpha4beta3gamma2 receptors and as a low-efficacy inverse agonist at alpha1beta3gamma2, alpha2beta3gamma2, and alpha5beta3gamma2 receptors. The present study indicates that betaCCt is capable of antagonizing the reinforcing and the sedative properties of alcohol. These anti-alcohol properties of betaCCt are primarily mediated via the GABA(A1) receptor. betaCCt may represent a prototype of a pharmacotherapeutic agent to effectively reduce alcohol drinking behavior in human alcoholics.

Alcoholism↗

Evaluation of the reinforcing effects of monoamine reuptake inhibitors under a concurrent schedule of food and i.v. drug delivery in rhesus monkeys.

Most medications prescribed for attention-deficit-hyperactivity disorder are psychomotor stimulants with reinforcing effects in laboratory animals (eg methylphenidate). The present studies were conducted to evaluate the reinforcing effects of the recently approved medication atomoxetine in monkeys trained to 'choose' between automated deliveries of either an i.v. injection or food. Rhesus monkeys were trained to lever-press under concurrent schedules of reinforcement; responses on one lever resulted in an injection of either saline or drug, and responses on the alternative lever resulted in food delivery. Data were collected on four measures: response rates, percentage of total responses occurring on the injection-lever (% ILR), number of injections earned, and number of food pellets earned. Dose-effect functions were determined for cocaine (0.003-0.3 mg/kg/inj), methylphenidate (0.003-0.1 mg/kg/inj), amphetamine (0.003-0.1 mg/kg/inj), atomoxetine (0.01-0.3 mg/kg/inj), and desipramine (0.03-1.0 mg/kg/inj) using a double alternation schedule of saline and drug availability. Results indicate that the distribution of behavior changed according to the drug and dose available for self-injection. Saline availability was typically associated with high rates of food-maintained responding. The % ILR increased from 3+/-1% when saline was available to >90% when >0.03 mg/kg/inj of cocaine, methylphenidate or d-amphetamine was available. However, no dose of atomoxetine or desipramine maintained self-administration behavior on the injection-lever. The number of food pellets earned per session decreased as the dose of each drug increased, indicative of behavioral activity with all five drugs. The reinforcing effects of cocaine, methylphenidate, and d-amphetamine in these studies are consistent with previous findings in nonhuman primates and with their documented abuse liability. The absence of reinforcing effects of atomoxetine support the view that, like desipramine, it has no evident abuse potential.

Adrenergic Uptake Inhibitors↗

Visual reinforcement of head-turn responses in infants under 12 months of age.

The effect of complex visual reinforcement (animated toy animal) on auditory localization responses of infants below 12 months of age was studied. Sixty infants served as subjects and each subject received 30 presentations of complex noise at suprathreshold level. After each response to an auditory signal, one-half of the infants (experimental group) received complex visual reinforcement and the other half (control group) received no reinforcement. The experimental and control groups were further subdivided into three age groups: four months, five and six months, and seven to 11 months. Visual reinforcement produced significantly more responses (head turn) than no reinforcement for the two older age groups. There was no significant difference between the experimental and control conditions at four months of age.

Age Factors↗

Reinforcing, subjective, and psychomotor effects of sevoflurane and nitrous oxide in moderate-drinking healthy volunteers.

AIMS: To characterize the reinforcing, subjective and psychomotor effects of sevoflurane, a volatile anesthetic, across a range of subanesthetic concentrations in non-drug-abusing humans. In addition, a concentration of nitrous oxide was included in the design in order to compare and contrast behavioral effects of a gaseous to a volatile anesthesic. DESIGN: Repeated measures, double-blind, placebo control experiment. SETTING: Human psychopharmacology laboratory. PARTICIPANTS: Fourteen moderate-drinking healthy volunteers. INTERVENTION: In each of four sessions, subjects first sampled placebo-oxygen and an active drug (end-tidal concentrations of 0.2, 0.4, 0.6% sevoflurane and 30% nitrous oxide in oxygen) and then chose between the two MEASUREMENTS: Mood and psychomotor performance during the sampling trials, and choice of drug or placebo-oxygen during choice trial. FINDINGS: Nitrous oxide was chosen by 71% of the subjects, and 0.2, 0.4 and 0.6% sevoflurane were chosen by 50%, 57% and 50% of the subjects, respectively. Neither drug was chosen at levels that exceeded that of chance. Sevoflurane and nitrous oxide both impaired psychomotor performance and produced changes in mood. There were several differences in subjective effects between sevoflurane and nitrous oxide at concentrations which were considered to be equivalent in anesthetic effect. Finally, although sevoflurane did not function as a reinforcer in the majority of individuals tested, there was evidence that sevoflurane functioned as a reinforcer in some volunteers: subjects who chose to inhale sevoflurane over placebo-oxygen tended to report a positive spectrum of subjective effects during the sevoflurane sampling trial, relative to those subjects who chose placebo-oxygen over sevoflurane. CONCLUSIONS: Although sevoflurane did not function as a reinforcer in the majority of subjects tested, the correspondence between positive subjective effects of sevoflurane and subsequent sevoflurane choice suggests that the volatile anesthetic drug can function as a reinforcer in some moderate drinkers.

Adult↗