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Results for “Reinforcement Schedule”

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PubMed1986

Effects of pimozide on emitted force, duration and rate of operant response maintained at low and high levels of required force.

The behavioral effects of pimozide (0.25, 0.5, and 1.0 mg/kg) were assessed in two separate experiments in which session mean peak force, maximum peak force, and response duration served as the dependent variables complementing operant response rate. In the first experiment, two groups of water-deprived rats were trained on a continuous reinforcement (CRF) schedule for reaching out and pressing downward on a force transducer with peak forces of at least 4 g (low-force group) or 40 g (high-force group). In the second experiment a pull-type response topography and fixed ratio 20 were used, and force requirements were 4 g for the low-force group and 100 g for the high-force condition. Under these conditions pimozide decreased response rate and increased response duration irrespective of response topography, required force, or schedule of reinforcement. Neither mean peak force nor maximum peak force were significantly decreased by the drug, and in the low-force CRF condition a small but significant dose-related rise in mean peak force was observed. It was hypothesized that neuroleptics exert their motor-impairing effects primarily in the temporal domain of behavior but do not appreciably affect the force dimension of performance capacity. And these temporal domain effects may be reflected in differences in the kinetic requirements for the overall behavior and not just the response itself. Additionally, the possibility that some of the observed effects could be accounted for by "anhedonia" was addressed.

Animals↗

PubMed1986

Chronic exercise produces tolerance to muscarinic antagonists in rats.

Previous work has shown that exercise can modify behavioral sensitivity to antimuscarinic compounds. The present study examined the effect of 10 weeks of endurance exercise on atropine and scopolamine potency. The behaviorally disruptive effects of these compounds were evaluated in rats trained to respond under a MULT TO FR30 schedule of reinforcement for food reward. Following 10 weeks of endurance exercise, atropine and scopolamine dose response curves were significantly altered. The ED50 values were increased 10 and 40-fold, respectively. Tolerance to atropine or scopolamine has been reported previously only in response to chronic drug administration. The present data demonstrate that non-drug factors can significantly influence behavioral response to muscarinic antagonists.

Animals↗

PubMed1987

Heroin self-administration: effects of antagonist treatment in lateral hypothalamus.

The involvement of the lateral hypothalamus and medial prefrontal cortex in mediating heroin self-administration was examined by means of intracranial microinjections of the quaternary opiate antagonist methyl naltrexone over a dose range of 0-3.0 micrograms. In animals trained to respond on a continuous reinforcement schedule for intravenous heroin (0.03 mg/kg/infusion), microinfusions of antagonist into the lateral hypothalamus prior to a self-administration session produced significant dose-related increases in responding on the drug manipulandum, similar to increases in responding observed after treatment with naltrexone systemically. Microinfusions of quaternary antagonist into the medial prefrontal cortex over the same dose range effective in the lateral hypothalamus did not produce response increases. These data suggest that opiate action in the lateral hypothalamus, but not in the medial prefrontal cortex, is salient in maintenance of intravenous self-administration.

Animals↗

PubMed1988

The effects of apomorphine on the acquisition of schedule-induced polydipsia in rats.

Injections of the dopamine agent, apomorphine, at the doses of 0.05, 0.50 and 1.0 mg/kg were given to three different groups of rats while a fourth group received an injection of the drug vehicle. The injections preceded each of 15 schedule-induced polydipsia (SIP) acquisition sessions in which the subjects bar-pressed for food pellets on a fixed interval 60-sec schedule of reinforcement. The vehicle-injected group developed SIP over sessions while each dose of apomorphine suppressed the acquisition of SIP. Bar-press rates were also depressed at the higher doses, while response patterning was affected at the lower dose. The results support the contention that a normally functioning dopamine system is necessary for the acquisition of SIP, but they do not support the view that this neurotransmitter system is specifically involved in the generation of SIP.

Animals↗

PubMed1988

Gamma-butyrolactone's discriminability and effect on low rates of lever pressing by rats: alone and in combination with D-amphetamine and naloxone.

Three studies examined gamma-butyrolactone (Gbl) for benzodiazepine-like effects on low rates of food reinforced lever pressing by rats. A fourth study established Gbl's discriminative properties. Additionally, d-amphetamine or naloxone was administered with Gbl to test hypotheses of Gbl's neurochemical mechanisms of action. In Experiment 1, Gbl caused a dose-related decrease in lever pressing during a fixed-interval reinforcement schedule. Contrary to previous reports, neither d-amphetamine nor naloxone reversed the depressive effects of a high dose of Gbl on behavior. In Experiment 2, Gbl increased lever pressing which had been suppressed in the presence of a tone correlated with response-independent foot-shock (conditioned suppression). These results are consistent with, and extend, previous findings of benzodiazepine-like antipunishment effects of Gbl. However, in Experiment 3, when brief electric shocks were presented after each lever press, Gbl did not increase lever pressing. These results show the limited generality of Gbl's antipunishment effect compared to broad spectrum anxiolytics. Experiment 4, a drug discrimination study, showed rats readily discriminated 150 and 125 mg/kg Gbl from saline. However, neither d-amphetamine nor naloxone generalized to the Gbl lever. Amphetamine partially blocked the discriminative properties of 150 mg/kg Gbl, whereas naloxone had little effect on Gbl's discriminative properties. Thus, there is some support for a direct catecholaminergic role in Gbl-related seizures and little support for opioid receptor participation. The results of Experiments 1 and 4 indicate that Gbl's effects on behavior are complex, and are not accounted for by hypotheses involving only catecholamine and/or opioid mechanisms of action.

4-Butyrolactone↗

PubMed1991

Acute effects of oral pyridostigmine bromide on conditioned operant performance in rats.

Pyridostigmine bromide (Pyr), the current drug of choice in the management of myasthenia gravis, has been suggested for use in Alzheimer's dementia, and as a prophylactic treatment for intoxication with organophosphate cholinesterase inhibitors. The present study was undertaken to evaluate the dose-response and time-course effects of acute oral administration of Pyr over a broad dose range (3-40 mg/kg) on the lever pressing of rats maintained under a multiple fixed-ratio (FR-20) time-out schedule of reinforcement for water reward. The drug produced a dose-dependent biphasic response depression in the overall rate of FR responding. Low doses of Pyr (less than or equal to 12 mg/kg) that caused no gross signs of toxicity only moderately decreased rates of responding, primarily due to a decrease in response rates. Whereas high doses of Pyr (greater than 24 mg/kg) which produced overt signs of peripheral cholinergic intoxication markedly suppressed overall responding, primarily due to cessation of responding. The lowest effective dose of performance disruption was 6 mg/kg, and the ED50 was calculated as 23.3 (17.9-28.7) mg/kg. The time-course data of performance disruption showed that low doses of Pyr (less than or equal to 12 mg/kg) had an onset latency within 40-80 min and a duration of 20-80 min, whereas high doses (greater than or equal to 24 mg/kg) had an onset latency of 20-40 min and a duration greater than 80 min. These results suggest the recommended human therapeutic or prophylactic regimen of 30-120.mg Pyr, orally taken each 8 hours, might adversely affect behavioral performance.

Administration, Oral↗

PubMed1991

Acute effects of the organophosphate paraoxon on schedule-controlled behavior and esterase activity in rats: dose-response relationships.

The effects of acute intraperitoneal administration of paraoxon on behavioral and biochemical parameters were studied in male rats. Rats were trained to press a lever under an FR10 schedule of reinforcement. Rats were injected with 3 sublethal doses of paraoxon (0.5, 0.75, and 1.0 mg/kg) and performance was monitored for four days after exposure. Response rates were depressed significantly for days 1 and 2 with 0.75 and 1.0 mg/kg, but not 0.5 mg/kg, even though there was inhibition of brain and plasma cholinesterases at all doses. Performance recovered prior to brain AChE recovery. There was no clear-cut threshold of brain AChE inhibition required to yield performance deficits, nor was there a direct correlation between significant inhibition in peripheral enzymes which could serve as markers (plasma aliesterases, butyrylcholinesterase, non-iso-OMPA-sensitive cholinesterase, and hepatic aliesterases) and performance deficits, suggesting that other noncholinergic targets may play a role in OP-induced behavioral deficits.

Acetylcholinesterase↗

PubMed1992

Drug-drug heart rate conditioning in rats: effective USs when pentobarbital is the CS.

Injections of two drugs in sequence may be considered the Pavlovian pairing of one drug as a conditioned stimulus (CS) with a second drug as an unconditioned stimulus (US). If pentobarbital was the CS and d-amphetamine or nicotine sulfate the US, then after about four drug-drug pairings the pentobarbital CS produced a higher heart rate (HR) than control conditions. With the same pentobarbital CS, HR conditioning was not obtained with the following USs: atropine, caffeine, lithium chloride, continuous foot-shock, and intermittent foot-shock. Although amphetamine and nicotine are pharmacologically different, a common conditioning mechanism seems indicated because of striking similarities in their parametric effects as USs. There also were strong similarities in these two USs when the conditioned response was a reduced capacity of the CS drug to produce conditioned taste aversions.

Amphetamine↗

PubMed1992

Titrating matching-to-sample performance: effects of drugs of abuse and intertrial interval.

Previous reports have shown that increasing the length of the intertrial interval (ITI) in a matching-to-sample schedule of reinforcement results in increased matching accuracy. This has traditionally been interpreted in the context of proactive inhibition, the disruption of memory for a stimulus as a consequence of events that occurred prior to the presentation of the stimulus. In an effort to more fully characterize a titrating matching-to-sample baseline, the effect of ITI ranging from 0-30 s was determined in pigeons trained to respond under the titrating matching-to-sample procedure. In addition, the effect of ITI length on the dose-response curve for pentobarbital, phencyclidine, D-amphetamine, and cocaine were determined. Surprisingly, performance under the titrating matching-to-sample was not altered as a function of ITI length, nor did the effects of the four drugs of abuse change as a function of ITI length. These results suggest that performance under the titrating matching-to-sample is under a different control than matching-to-sample using fixed delays.

Amphetamine↗

PubMed1992

Effect of diazepam on successive negative contrast in one-way avoidance learning.

The effect of administration of diazepam on successive negative contrast in one-way avoidance learning was examined in rats. Contrast was induced by shifting rats from a large reward, 30 s spent in the safe compartment, to a small reward, 1 s spent in the safe compartment. IP administration of 2 mg/kg diazepam eliminated this negative contrast. Moreover, this effect is dose dependent, with doses of 2 and 2.5 mg/kg, but not 0.5 mg/kg, effective in reliably reducing contrast. These results suggest the existence of similar or common underlying mechanisms in both aversive and appetitive contrast effects; they are discussed in light of the current theories of frustrative nonreward and as a mean of studying the behavioral and biological mechanisms of anxiety.

Animals↗

PubMed1993

Housing conditions influence acquisition of sufentanil aerosol self-administration in rats.

At weaning, rats were housed either individually or in pairs and as adults were trained to poke their nose in and out of a port that dispensed a 2-s exposure of sufentanil aerosol (50-micrograms/ml solution). During the acquisition phase, which consisted of five nightly sessions lasting 14-16 h, individually caged rats responded for more sufentanil aerosol than did pair-caged animals when the fixed ratio (FR) requirement was gradually increased from FR 1 to FR 5 over the five sessions. During the maintenance phase, which consisted of daytime 2-h sessions at an FR 5 schedule of reinforcement, there were no differences between individually and pair-caged animals responding for sufentanil or for water vapor. Both groups responded significantly more for sufentanil than for water vapor. Based upon present evidence, it is suggested that environmental and biologic determinants may change psychomotor behavior in a way that could influence the rate by which animals acquire drug-seeking behavior.

Aerosols↗

PubMed1993

Water deprivation-induced oral self-administration of cocaine in the Lewis rat: evidence for locomotor effects but not reinforcement.

Oral cocaine self-administration was studied in water-deprived Lewis rats. Liquid was available to rats only during daily 90-min sessions, in chambers equipped with spouts that delivered precise volumes of liquid following completion of lever-press responses. Blocks of training and testing sessions were alternately carried out during which increasing cocaine concentrations were presented: 0.0, 0.0125, 0.025, 0.05, 0.1, 0.2, 0.282, and 0.4 mg/ml. Although high cocaine intakes (23.3-33.0 mg/kg) were obtained, neither avoidance nor preference for cocaine developed. Subsequently, fixed-ratio size was increased, and then distinctive stimulus lights were correlated with each liquid. One rat showed a preference for water following these changes, but two rats continued to show no preference. To determine if the amounts of cocaine self-administered had behavioral effects, locomotor activity tests were run immediately following self-administration sessions. Locomotor activity was substantially higher following cocaine self-administration than following water self-administration. These results demonstrate that the cocaine intakes reached under the present conditions did produce locomotor, but not reinforcing, effects.

Animals↗

PubMed1995

Linopiridine (DUP 996; AVIVA): its effects in the Morris water escape tank and on retention of an incompletely acquired bar-press response in rodents.

The present study assessed the effects of linopirdine, a putative cognition-enhancing drug, on the acquisition and retention of a bar-press response [continuous reinforcement schedule (CRF)] in young Wistar rats. It was also investigated whether this substance influenced the acquisition and retention of a standard Morris water escape tansk by young NMRI mice and by young and old Wistar rats. Linopirdine was given subcutaneously (0.03, 0.1, 0.3, 1.0, or 3.0 mg/kg body wt.), 30 min before the first trial of a session and in one experiment immediately after the the last trial of each session. A probe trial was given after the last acquisition session. In the CRF task, linopirdine did not affect the response latency and the 24-h retention of young rats. None of the parameters investigated in the Morris maze, including the escape latency (the time the animals need to find the platform), was affected by linopirdine in the rat and mouse experiments. This was also true for performance in the probe trial: linopirdine treatment did not affect the bias of the animals for the quadrant in which the platform had been positioned during acquisition. Thus, we found no experimental evidence for the hypothesized action of linopirdine as a cognition enhancer.

Aging↗

PubMed1994

Antagonist-precipitated opioid withdrawal in rats: evidence for dissociations between physical and motivational signs.

In rats made opioid dependent by the implantation of a single morphine 75 mg base pellet, an attempt was made to determine whether any correlational existed between physical and motivational withdrawal signs by adjusting the dose of naloxone used to precipitate withdrawal. The models used to study motivational signs were taste (one- and two-bottle) conditioning and operant responding for food under an FR15 schedule of reinforcement. Naloxone at doses of 0.01 mg/kg and above produced both a conditioned taste aversion (two-bottle test only) and reduced food responding in morphine pellet, but not placebo pellet, implanted animals. No physical withdrawal signs, e.g., wet dog shakes, diarrhoea, were noted until naloxone doses of 0.05 mg/kg and above were used. It is concluded that the difference in naloxone doses required to elicit physical and motivational withdrawal components provides further support for their dissociation.

Animals↗

PubMed1994

Failure of ritanserin to block the discriminative or reinforcing stimulus effects of cocaine.

Ritanserin, a 5-HT2/1C antagonist, has been suggested to reduce the preference for cocaine in rats. In the present experiment, the action of ritanserin was investigated in locomotor activity, cocaine drug discrimination, and cocaine self-administration paradigms in rats. A low dose of ritanserin (1.0 mg/kg) was without effect on locomotor activity, while a higher dose (10.0 mg/kg) reduced both horizontal and vertical locomotor activity counts during the first 30 min of the test session. Ritanserin (0.32-32 mg/kg) did not significantly affect the discrimination of 10 mg/kg of cocaine, nor did a dose of 10.0 mg/kg significantly modify the dose-effect curve for cocaine discrimination. Ritanserin (1.0 and 10.0 mg/kg) had no significant effect on the dose-response curve for cocaine self-administration. Thus, ritanserin was without effect against either the discriminative or reinforcing stimulus effects of cocaine, suggesting that ritanserin has limited efficacy as a potential treatment for cocaine abuse.

Animals↗

PubMed1995

Reinforcing and discriminative stimulus effects of beta-CIT in rhesus monkeys.

beta-CIT (also designated RTI-55) is one of a series of 2 beta-carbomethoxy-3 beta-phenyltropane cocaine analogues that have recently been synthesized for characterizing the dopamine transporter and its function. The present study was designed to examine the behavioral effects of beta-CIT in rhesus monkeys. Two monkeys were allowed to self-administer cocaine (0.01 or 0.03 mg/kg/inj, IV, fixed-ratio 10, 1 h/day) in baseline sessions. When behavior was stable, beta-CIT (0.0007-0.003 mg/kg/inj, IV) was made available for self-administration for several consecutive sessions. beta-CIT maintained responding above saline levels in both monkeys. Two other monkeys were trained to discriminate cocaine (0.2 or 0.4 mg/kg, IM) from saline in a two-lever, food-reinforced drug discrimination paradigm. beta-CIT (0.012-0.025 mg/kg, IV) fully substituted for cocaine as a discriminative stimulus. In both preparations, beta-CIT was at least eightfold more potent than cocaine and had a longer duration of action. Thus, beta-CIT has cocaine-like behavioral effects indicative of a functional interaction with the dopamine transporter.

Animals↗

PubMed1995

Intravenous cocaine self-administration in the C57BL/6J mouse.

Freely behaving C57BL/6J mice with intrajugular catheters were trained to nose-poke for cocaine (0.75 mg/kg per 5-microliters infusion) under a fixed-ratio-10 schedule of reinforcement. Mice were given a choice between two nose-poke holes on opposite sides of the apparatus. Nose-pokes by experimental (O) subjects (operant group) were reinforced on only one side and reinforcer delivery coincided with the onset of a 10-s time-out light stimulus. Drug delivery to control subjects (yoked group) was determined by the behavior of O mice. Nose-poke rate increased in O subjects, whereas yoked subjects did not acquire the nose-poking response. Moreover, nose-poking was selective for the cocaine-paired side in O subjects. When saline infusions were substituted for cocaine (i.e., extinction), nose-poking in O subjects decreased, whereas yoked controls were unaffected. O subjects developed a preference for the drug-associated side of the apparatus during extinction. Overall, these data offer strong evidence of cocaine-directed behavior in the C57BL/6 inbred mouse strain. More generally, these findings support the feasibility of using intravenous self-administration to assess reinforcement in genetically well-defined populations.

Animals↗

PubMed1996

Behavioral effects of naloxone on neuropeptide Y-induced feeding.

We evaluated the effect of naloxone on neuropeptide Y (NPY)-induced feeding behavior using two methods; operant chambers and observational analysis. In the first study rats were trained on a FR 80 (first pellet) FR 3 (subsequent pellets) reinforcement schedule. Following training, rats were injected with NPY (intraventricular, 5 micrograms) and various doses of naloxone (subcutaneous, 0, 0.1, 0.3, 1, 3, and 10 mg/kg). NPY significantly increased the number of pellets consumed during the one hour session and naloxone (1, 3, and 10 mg/kg) blocked this effect. NPY failed to alter the time to the first response, but did decrease the time needed to complete the first ratio (FR 80). Naloxone (3 and 10 mg/kg) increased the latency to the first response and blocked NPY's effect on completion of the first ratio. In the second study, we observed rats continually following injection of saline. NPY (5 micrograms i.c.v.) and/or naloxone (1 mg/kg s.c.). NPY increased food intake during the 1-h session and naloxone blocked this effect. NPY decreased the latency to eat, but naloxone failed to significantly antagonize this effect. The amount of time spent eating was greater in the NPY group compared to the saline group and naloxone antagonized this effect. Lag sequential analysis indicated that NPY induced a move-eat-move behavioral sequence that disappeared following naloxone administration. These data lend support to the notion that opioids are involved in maintenance of NPY-induced feeding but affect meal initiation in a minor way. Only relatively high doses of naloxone (3 and 10 mg/kg) altered NPY-induced changes in meal initiation.

Animals↗