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PubMed1997

Repeated administration of flumazenil does not alter its potency in modifying schedule-controlled behavior in chlordiazepoxide-treated rhesus monkeys.

Previous reports have suggested that the effects of the benzodiazepine antagonist flumazenil diminish over repeated exposure in subjects treated chronically with a benzodiazepine agonist. The current study examined whether the frequency of exposure to flumazenil altered its potency in decreasing rates of responding in monkeys treated with chlordiazepoxide (CDP). Three monkeys responded under a multiple fixed ratio (FR10:FR10) schedule of food presentation and stimulus-shock termination (SST). In untreated monkeys, flumazenil (0.1-3.2 mg/kg) had no effect in either component. After 2 weeks of treatment with 32.0 mg/kg per day of CDP, flumazenil decreased response rates in the food component, with a dose of 3.2 mg/kg decreasing rates to 10% of control; rates in the SST component were not altered by flumazenil. When flumazenil dose-effect curves were redetermined at 28-, 14-, 7-, 4-, 2- or 1-day intervals, there was no further change in the potency of flumazenil in decreasing food-maintained responding. When CDP treatment was terminated, the potency of flumazenil recovered to pre-CDP values within 23 days. These results suggest that dependence develops to CDP, since changes in the potency of flumazenil co-varied with CDP treatment. Moreover, it does not appear as though results from previous reports, that showed a diminished response to frequently-administered flumazenil, can be generalized to all conditions.

Animals↗

PubMed1990

Effects of cocaine on locomotor activity and schedule-controlled behaviors of inbred rat strains.

Effects of cocaine on several behaviors considered to be reflective of psychomotor stimulation were compared in F344/CR1BR and NBR/NIH inbred rat strains. Effects of cocaine on locomotor activity were compared with effects on either bar-press or nose-poke responses maintained under a multiple fixed-interval 3-min, timeout 1-min schedule of food presentation. In locomotor activity experiments, NBR rats were twice as active as F344 rats under baseline conditions and displayed dose-dependent increases in locomotion (5-20 mg/kg). Maximal increases in locomotor activity of F344 rats were only 200% compared to 1000% in NBR rats. In contrast to locomotor activity, no strain differences in the effects of cocaine were observed under the schedules of food delivery. Bar-pressing under the fixed-interval schedule was increased to a maximum of 150% of control in both rat strains. Nose-poke responding under the fixed-interval schedule was not significantly increased, but timeout rates were increased in both strains. These results suggest that NBR and F344 rats do not differ in general sensitivity to stimulant effects of cocaine but exhibit marked differences in responsivity to cocaine that are dependent upon the behavior studied. Further delineation of the behavioral specificity of strain differences in sensitivity to cocaine should help to identify neurobiological substrates underlying unique biologically determined responses to cocaine.

Animals↗

PubMed1988

Influence of stressor predictability and behavioral control on lymphocyte reactivity, antibody responses and neuroendocrine activation in rats.

The present experiments were designed to study the influence of prediction and control of electric shocks on various aspects of immune function, and the possible intermediate role of glucocorticoid hormones. After two sessions of inescapable footshocks, the reactivity of splenocytes to concanavalin A was reduced by one third. This effect was completely reversed when each shock was preceded by a warning stimulus, even though the adrenocortical response was the same in both conditions. In another experiment, rats were submitted to ten sessions of continuous avoidance in a shuttle-box and a group of yoked animals received the same footshocks without any relationship to their shuttling behavior. Although yoked rats displayed a reduced reactivity of splenocytes to lectins, animals of the avoidance group had a reduced antibody response to sheep erythrocytes. In contrast, no difference was observed in the corticosterone or prolactin response. These data further support the importance of psychological factors on stress-induced changes in immune functions. Furthermore, they demonstrate that various aspects of the immune system are differentially affected by behavioral factors and the results argue against a major role for the adrenocortical system in mediating these changes.

Adaptation, Psychological↗

PubMed1993

Effects of repeated administration of corticotropin-releasing factor on schedule-controlled behavior in rats.

To examine the effects of repeated administration of corticotropin-releasing factor (CRF) on behavior, rats were administered ICV injections of either CRF or saline on alternate days for 10 days prior to performing on a multiple fixed-interval (FI) 60 s/fixed-ratio (FR) 20 schedule for food reinforcement. A daily session consisted of 10 components of each schedule that alternated, starting with the FI component. CRF doses were individually determined for each rat and were either 1.0, 3.0, or 10 micrograms CRF based upon the dose that occasioned more than a 50% reduction in the rate of responding. Acute administration of CRF decreased the rate of responding in both components well below control rates; this decrease in responding was associated with a 20 or 50% decrease in the number of earned reinforcements in the FI and FR components, respectively. With repeated administration, CRF-induced suppression of responding was attenuated, although CRF continued to decrease response rate. Despite the continued reduction in response rate, subsequent CRF injections did not result in a loss of reinforcements in the FI component, whereas rats continued to lose 20% of the reinforcers in the FR component. After an 18-day hiatus in which no CRF was administered, the baseline rate of responding on the multiple schedule increased, in particular in the FI component. When CRF was readministered, response rates were slightly suppressed relative to a reestablished saline control but significantly higher than CRF-induced suppression on the last day of the chronic regimen. These data demonstrate that with repeated administration tolerance develops to CRF-induced suppression of responding in rats.

Animals↗

PubMed1982

Maintenance of schedule-controlled behavior by intravenous injections of nicotine in squirrel monkeys.

Lever pressing by squirrel monkeys was maintained by i.v. injections of nicotine (3-560 microgram/kg) or cocaine (3-300 microgram/kg) under two intermittent schedules of self-administration. Under a fixed-interval schedule, the first response after a specified interval of time produced an injection. Under a second-order fixed-interval schedule, the completion of every 10-response fixed-ratio unit produced a brief visual stimulus and the first fixed-ratio unit completed after a specified interval produced both the brief stimulus and an injection. As the dose of either drug was increased, the rate of responding first increased and then decreased; maximal response rates maintained by nicotine were approximately equal to those maintained by cocaine in some monkeys, but less than those maintained by cocaine in other monkeys. Patterns of responding maintained by the two drugs were qualitatively similar in all monkeys and were characteristic of performances maintained by other reinforcers under fixed-interval or second-order fixed-interval schedules. Doses of nicotine greater than 30 microgram/kg/injection usually produced vomiting, but often maintained responding well above the rates maintained by saline. When the nicotinic antagonist, mecamylamine (1.0 mg/kg i.m.) was administered before every experimental session, responding maintained by nicotine, but not by cocaine, fell to within saline-control levels; increasing the dose of nicotine to as high as 1700 microgram/kg/injection did not restore responding. Under the intermittent schedules studied here, nicotine served as an effective reinforcer to maintain responding and the reinforcing effects of nicotine were blocked by mecamylamine.

Animals↗

PubMed1967

Behavioral control by an imprinted stimulus: long-term effects.

Newly hatched ducklings were exposed to imprinting procedures and subsequently trained to peck a key by presenting the imprinting stimulus as the reinforcing (response-contingent) event. Individual ducklings then lived in the apparatus under an arrangement in which each peck produced a 15-sec stimulus presentation. For all ducklings, key-pecks tended to occur in bursts, and as the duckling matured, burst length decreased and the interval between bursts increased. However, even when subjects were 60 days old, some responses still occurred.

Animals↗

PubMedDate not supplied

The effects of dopamine agonists on fixed interval schedule-controlled behavior are selectively altered by low-level lead exposure.

A previous report of differential effects of catecholaminergic compounds, but not other classes of compounds, on FI (fixed interval) response rates of lead (Pb)-treated pigeons suggests that catecholamine system disturbances might play a role in lead (Pb)-induced changes in FI performance. The current study sought to extend those findings using more selective dopaminergic (DA) D1 and D2-like receptor agonists, Pb-treated rats, and additional classes of compounds. Drug-induced changes in FI performance of rats exposed chronically from weaning to 0, 50, or 150 ppm Pb acetate in drinking water were compared following the administration of drugs known to impact various neurotransmitter systems altered by Pb exposure, including the selective D2-like agonist quinpirole, the D1 agonists SKF38393 and SKF82958, the mu-opioid agonist morphine, the muscarinic cholinergic agonist arecoline, the glutamate agonist NMDA, and the noncompetitive NMDA antagonist MK-801. All drugs except NMDA significantly altered FI performance, but only the effects of DA agonists differed in control and Pb-exposed rats. Pb exposure attenuated the decrements in rates produced by D1 agonists and at 150 ppm modestly altered the rate changes associated with low doses of quinpirole. These data demonstrate functional DA alterations in response to Pb exposure and provide further evidence for the selective involvement of such effects in FI performance.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1989

[Associative brain systems as the behavioral control apparatus based on the dominant and conditioned reflex].

The main statements of author's conception concerning the associative brain systems (thalamoparietal and thalamofrontal) as the behaviour control systems are presented. The participation of associative systems in performance of the high brain functions ensures due to the entrance of the whole information spectrum of biological and signal significance into them and to the presence of neuronal plastic mechanisms, the mechanisms for retrieval the whole behaviour programs from the long-term memory and the ability of short-term storing of behaviour programs and estimation of their adequacy on the ground of dominant and conditioning mechanisms.

Animals↗

PubMed1992

Rat exploratory behavior controlled by intracranial self-stimulation improves the study of place cell activity.

This report is limited to the description of a procedure that should help to resolve the question whether firing fields of hippocampal place cells are relatively stable or modifiable by learning. Rats implanted with lateral hypothalamic electrodes for rewarding intracranial self-stimulation (ICSS) were trained to explore a circular open field (100 cm in diameter) while their locomotion was tracked by a computerized video system which also delivers ICSS whenever the animal's exploration has met certain experimenter defined criteria. The 3 following conditions were examined. (1) Homogeneous exploration of the entire field: ICSS was delivered after the animal repeatedly visited 5 equal segments of the field (central annulus and remainders of the 4 quadrants), entered randomly located circular areas of the field, and/or traveled a criterion distance. (2) Place field contingent reward or non-reward: ICSS was delivered when the animal entered a circular area (23 cm in diameter) corresponding to the place field after a previous visit to a similar area outside the place field. These conditions were reversed in the following task. (3) Delayed reward: ICSS was delivered when the animal entered the circular area and remained in it for 2 s. Each condition was tested for 600 s or until 50 ICSS were delivered. The behavioral procedures described make it possible to propose an experimental protocol that allows examination of the same place cell under conditions of homogeneous exploration with a segment condition or randomly distributed reward and under conditions with the place field signaling reward or non-reward. The delayed reward condition increases the accuracy of the target location and allows assessment of the phasic versus tonic nature of the place cell firing.

Animals↗

PubMed1981

Effects of phencyclidine, d-amphetamine and pentobarbital on schedule-controlled behavior in rats.

The effects of phencyclidine, d-amphetamine, and pentobarbital on responding maintained under a multiple fixed-interval (FI) 3-min fixed-ratio (FR) 30 schedule of food presentation were studied in rats. Phencyclidine (0.32-7.5 mg/kg) had a biphasic effect on overall response rate in both components; response rate increased and then decreased as the dose was increased. The FR was slightly more sensitive to the rate-decreasing effects of phencyclidine than the FI. The effects of d-amphetamine (0.1-7.5 mg/kg) on overall response rate were qualitatively similar to those of phencyclidine. The FI tended to be slightly more sensitive than the FR to the rate-increasing effects of d-amphetamine. Pentobarbital (1-18 mg/kg) produced little or no rate-increasing effects in the FR at low doses and decreased FR response rate at higher doses. In the FI, pentobarbital produced small increases in overall rate at intermediate doses while decreasing response rate at higher doses. The FR tended to be more sensitive than the FI to the rate-decreasing effects of pentobarbital. Unlike d-amphetamine and pentobarbital, phencyclidine produced smaller rate-increasing effects when the dose-effect curves were redetermined. Within the FI, the effects of phencyclidine and d-amphetamine on response rate were generally independent of the control rate of responding.

Animals↗

PubMed1979

The behavioral control of obesity: a descriptive analysis of a large-scale program.

Evaluated a behavoiral treatment program for 147 obese patients in a Weight Control Clinic. Weight losses during treatment averaged 11.01 pounds with large inter-S variability. Unlike past studies, patients continued to lose weight during a 6-month follow-up period. Weight loss was associated with age and initial degree of obesity, but other demographic and psychological variables failed to predict success in treatment. A critical examination of the attrition problem was carried out to determine the relationship between patient variables and the propensity to terminate treatment prematurely. Results demonstrate the utility of bahvioral treatment procedures for obesity, yet further research is needed to reduce attrition and to facilitate long-term maintenance of weight loss.

Adult↗

PubMed1992

Effects of self-generated rules on the development of schedule-controlled behavior.

College students responded under a multiple differential-reinforcement-of-low-rate 5-s fixed-ratio 8 schedule, with components alternating every 2 min. After 40 programmed minutes of acquisition and 12 min of maintenance, without notice, both schedules changed to extinction for 28 min. During acquisition, between alternations of the multiple schedule, some subjects were asked to develop rules describing the schedule contingencies. Other subjects were given these same rules between alternations, and a third group neither received nor were asked to develop rules. By the end of the acquisition phase, self-generated-rule subjects were more likely to show schedule-typical behavior than were subjects not asked to generate rules. The behavior of those given rules was similar to those asked to generate rules at the end of acquisition, but yoked-rule subjects acquired schedule-typical behavior at a quicker rate. By the end of extinction, during the period corresponding to the previous fixed-ratio interval, all no-rule subjects who had earned points during acquisition and maintenance were responding at a rate of less than 30 responses per minute. Only 3 of the 9 self-generated-rule subjects and 2 of the 5 yoked-rule subjects were similarly responding at this low rate. Results suggest that asking subjects to develop self-rules facilitates acquisition, but can retard extinction. Results also suggest that self-generated rules function similarly to external rules.

Adult↗

PubMed1990

Evaluation of the pharmacological similarities between phenylpropanolamine and amphetamine: effects on schedule-controlled behavior.

In an effort to determine the degree to which the repeated administration of phenylpropanolamine (PPA) results in the development of tolerance to its disruptive effects on operant responding as well as cross-tolerance to the effects of acutely administered amphetamine, water-deprived rats were first trained on a fixed-ratio 5 (FR-5) schedule for water presentation. Dose-response curves for the effects of PPA and amphetamine (administered IP, 15 min presession) were then determined (ED50 = 35.0 and 2.6 mg/kg, respectively) followed by the chronic administration of 40.0 mg/kg PPA (administered IP, 15 min prior to each session). When responding returned to prechronic rates, the dose-response curves were redetermined for both PPA (ED50 = 220 mg/kg) and amphetamine (ED50 = 4.8 mg/kg). In a second set of rats, trained under similar conditions, it was observed that pretreatment with alpha-methyltyrosine (AMT, 100 mg/kg IP, 2 h presession) antagonized the disruptive effects of both PPA and amphetamine, whereas pretreatment with reserpine (0.31 mg/kg, IP, 12 h presession) antagonized the disruptive effects of PPA, but exacerbated the disruptive effects of amphetamine. In a separate experiment, the repeated administration of PPA 100 mg/kg or 200 mg/kg IP resulted in no long-lasting depletions of rat striatal dopamine, serotonin, or 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations. These observations indicate that PPA and amphetamine share a similar mechanism of action to the degree that cross-tolerance develops, but which is nonetheless dissociable with respect to their differential sensitivity to antagonists and their neurotoxic efficacy.

Amphetamine↗

PubMed1993

Acute neurobehavioral effects of co-inhalation of toluene and n-hexane on schedule-controlled behavior in rats.

Whether coexposure to toluene and n-hexane had any combined effects on the shock avoidance performance in rats was studied. Eighteen Wistar male rats with an avoidance rate of over 80% were selected and divided to three groups based on performance and body weight: (1) toluene, (2) n-hexane, and (3) toluene + n-hexane. Each group was exposed alternately first to air and then to a particular organic solvent for 4 hr at various concentrations (50, 100, 200, 400, or 800 ppm, in ascending order). The effects of each organic solvent were evaluated by comparing the performance of rats during and after exposure with their own performance under the sham exposure to air by three-way ANOVA. The main results were that (1) 200, 400, or 800 ppm toluene exposures increased lever press rates, (2) 50 ppm n-hexane exposure decreased lever press and avoidance rates in a transitory manner and 800 ppm n-hexane exposure increased the lever press rate, (3) the 50 ppm mixture (25 ppm toluene + 25 ppm n-hexane) decreased lever press and avoidance rates persistently during and after the 4-hr exposure and the 800 ppm mixture (400 ppm toluene + 400 ppm n-hexane) decreased lever press and avoidance rates unpredictably when compared to the results of 400 or 800 ppm of toluene or n-hexane alone. In conclusion, n-hexane showed narcotic effects at 800 ppm and modified the acute neurobehavioral effects of toluene in rats at 400 ppm toward unpredictable results.

Administration, Inhalation↗

PubMed1987

Effects of ethylketazocine and morphine alone and in combination with naloxone on schedule-controlled behavior in pigeons.

The behavioral effects of morphine and ethylketazocine were compared in pigeons responding under multiple fixed-interval, fixed-ratio schedules of food presentation. Both morphine and ethylketazocine produced dose-related decreases in rates of responding maintained under either schedule. Maximal effects of morphine were observed about 15-45 min after injection and typically lasted the entire session (about 60 min). Effects of ethylketazocine had a faster onset (maximal effects were observed within 15 min after injection), and shorter duration (effects diminished within the session). Ethylketazocine and morphine had similar potencies. Dose-effect curves for both drugs were shifted to a similar degree by naloxone.

Analgesics, Opioid↗

PubMed1988

Opioid receptor subtype-specific cross-tolerance to the effects of morphine on schedule-controlled behavior in mice.

Key-press responding of mice was maintained under a fixed-ratio (FR) 30-response schedule of food presentation. Successive 3-min periods during which the experimental chamber was illuminated and the schedule was in effect were preceded by 10-min time-out (TO) periods during which all lights were out and responses had no scheduled consequences. Intraperitoneal (IP) injections of saline or of cumulative doses of drugs were given at the start of each TO period. Successive saline injections had little or no effect on response rates, whereas the mu-opioid agonists morphine (0.1-10.0 mg/kg) and levorphanol (0.1-3.0 mg/kg), the kappa-opioid agonist ethylketazocine (0.03-3.0 mg/kg), the mixed mu-/delta-opioid agonist metkephamid (0.1-10.0 mg/kg), and the nonopioid dissociative anesthetic ketamine (1.0-100.0 mg/kg) generally produced dose-related decreases in response rates. Following chronic administration of morphine (100.0 mg/kg/6 h), tolerance developed to the effects of morphine on rates of responding. In addition, a comparable degree of cross-tolerance developed to the effects of levorphanol and metkephamid. On the other hand, there was no evidence of cross-tolerance to the effects of ethylketazocine or ketamine. These results are consistent with the evidence suggesting that different opioid agonists exert their behavioral effects through distinct classes of opioid receptors.

Animals↗

PubMed1986

The effects of some putative antidepressant agents on the schedule-controlled behavior of the pigeon.

Numerous "second-generation" antidepressants with pharmacological profiles and chemical structures different from those of the tricyclic antidepressants have recently been developed. We examined the actions of four of these compounds (mianserin, maprotiline, trazodone and fluvoxamine) on the responding of pigeons under two different multiple (mult) schedules of grain presentation (a mult fixed-interval (FI) 600-s fixed-ratio (FR) 30-response and a mult FI 200-s FI 200-s in which responding in one component was punished by intermittent presentation of a brief electric shock). The rate of FI 600-s responding was greatly increased by several doses of maprotiline and mianserin, which either did not affect or produced only small increases in the rate of FR 30 responding. Fluvoxamine and trazodone did not produce similar differential effects. Relatively low doses of maprotiline, mianserin and trazodone decreased the FI quarter-lives. Fluvoxamine only decreased the FI quarter-life at a dose that largely eliminated responding. Mianserin produced proportionally greater increases in the rate of punished FI 200-s responding than in the rate of unpunished FI 200-s responding. Selective effects on punished responding were not seen with maprotiline, fluvoxamine and trazodone.

Animals↗

PubMed1987

Tolerance to antinociceptive effects of morphine without tolerance to its effects on schedule-controlled behavior.

The development of tolerance to behavioral effects of morphine was investigated in rats that responded on a two-lever, multiple-trial, multiple differential-reinforcement-of-low-rate fixed-ratio (mult DRL FR) schedule of food presentation. Stable performances were maintained when sessions were conducted just twice per week. The effects of cumulative doses of morphine (1.0-8.0 mg/kg) or chlordiazepoxide (CDP; 4.0-32.0 mg/kg) were evaluated once per week; saline injections were given in the intervening sessions. The effects of saline and morphine on nociception were also evaluated in hot-plate tests conducted on the same subjects 15 min after selected operant sessions. Initially, morphine produced dose-related decreases in response rates and reinforcement rates in the DRL and FR components as well as significant increases in hot-plate response latencies. Following weekly administration of morphine (1.0-8.0 mg/kg) for 10 weeks, there was little or no tolerance to its effects on operant behavior. In contrast, complete tolerance developed to the antinociceptive effects of morphine. These results suggest that tolerance to various behavioral effects of morphine may be dissociated, and that the loss of reinforcement may be insufficient by itself to produce tolerance to effects of morphine on operant behavior. Additionally, whereas CDP initially produced only dose-related decreases in DRL and FR response rates, following weekly morphine the smaller doses of CDP (4.0-16.0 mg/kg) produced increases in response rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗