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Biomedical subjects

M Galizio

Publications and source records attributed to M Galizio.

At least 19 recordsLinked to original sources

Chlordiazepoxide and dizocilpine, but not morphine, selectively impair acquisition under a novel repeated-acquisition and performance task in rats.

RATIONALE: Some classes of drugs can selectively affect learning (i.e., acquisition of behavior) at doses that do not affect performance (i.e., previously learned behavior). Some drugs (e.g., benzodiazepines) show selective effects on acquisition across a wide variety of tasks. Other drugs [e.g., N-methyl-D-aspartate (NMDA) antagonists and opiate agonists], however, show selective effects under some tasks, but not others. OBJECTIVES: The purpose of this study was to examine the effects of the NMDA-antagonist dizocilpine (0.01-0.3 mg/kg), the opiate-agonist morphine (1.0-17.0 mg/kg), and the benzodiazepine chlordiazepoxide (3.0-30.0 mg/kg) in rats under a novel repeated-acquisition and performance task. METHODS: Nose pokes to a correct location within a 2x3 stimulus array on a computer touch screen were reinforced with food. In the acquisition component, the correct location changed across sessions but remained constant within sessions; in the performance component, the correct location was constant both across and within sessions. RESULTS: Both chlordiazepoxide and dizocilpine selectively impaired accuracy in the acquisition component at doses that did not affect accuracy in the performance component or overall response speed. Morphine, however, did not affect acquisition without affecting performance or response speed. CONCLUSIONS: These results with rats resembled those previously obtained for response-sequence learning in primates, rather than those previously reported for spatial learning in rats. Therefore, previous discrepancies in results for NMDA antagonists and opiate agonists across tasks probably were not a function of the species studied, but, rather, they more likely were a function of unique variables controlling acquisition within each task.

Animals↗

Effects of positive GABA(A) modulators on a multiple-component, repeated-acquisition test of spatial learning.

The purpose of this study was to determine the effects of the benzodiazepines, midazolam and chlordiazepoxide, and the barbiturate, pentobarbital, on spatial learning, in a within-subject, repeated-acquisition and performance procedure adapted to the Morris Swim Task. In the presence of one stimulus arrangement, rats learned to swim to a hidden escape platform that was always in the same location in a swimming pool (performance component). In the presence of a second stimulus arrangement, the platform moved to a different place in the pool for each daily session (acquisition component). All subjects completed six training trials in both components during each daily training session, alternating between the two components within each session. Relatively direct paths to the platform and short escape latencies in the performance component, and steep within-session learning curves in the acquisition component, demonstrated that behavior under each component was controlled by the discriminative stimuli. All three GABA(A) modulators increased swim distances, escape latencies, and slowed swim speed in a dose-dependent manner. Midazolam and chlordiazepoxide, but not pentobarbital, produced selective impairments of swim distances and escape latencies in the acquisition component. Benzodiazepines disrupted acquisition at doses that did not disrupt steady-state performance. Pentobarbital impaired acquisition only at doses that also disrupted behavior during the performance component and reduced swimming speeds.

Animals↗

Clustering in artificial categories: an equivalence analysis.

Category clustering is a robust finding in the free recall of familiar category members, but has rarely been studied with artificial categories. In the present study, college students learned artificial categories via stimulus-equivalence methodology. Arbitrary match-to-sample training with nonsense syllables established three interrelated conditional discriminations, and, for most subjects, unreinforced test trials revealed the emergent stimulus-control relations considered to be evidence of equivalence classes. Free-recall tests revealed evidence of significant within-class clustering both before and after equivalence testing, but was more pronounced after the equivalence tests. These findings confirm that classic phenomena like clustering in free recall can be studied with stimulus-equivalence methodology, thus allowing for experimental control over relevant variables.

Adult↗

Acquisition of arbitrary conditional discriminations by young normally developing children.

Three experiments investigated conditions designed to facilitate acquisition of arbitrary conditional discriminations in 3- to 6-year-old normally developing children. In Experiment 1, 6 subjects failed to master the arbitrary match-to-sample task under conditions of differential reinforcement alone, but 7 subjects did so when instructions or instructions and sample naming were added. In Experiment 2, sample naming introduced in a blocked-trial arrangement resulted in acquisition, but only when the sample name was a nonsense syllable provided by the experimenter (5 of 7 subjects) and not when the sample name was generated by the subject (0 of 5 subjects). Experiment 3 demonstrated the effectiveness of a training sequence involving thematically related stimuli as an intermediate step facilitating the transition from identity to novel arbitrary relations. The difficulties in mastering arbitrary conditional discriminations shown here imply that further analyses with young children will be particularly important in efforts to investigate the development of theoretically important stimulus relations.

Child↗

Extinction of responding maintained by timeout from avoidance.

The resistance to extinction of lever pressing maintained by timeout from avoidance was examined. Rats were trained under a concurrent schedule in which responses on one lever postponed shock on a free-operant avoidance (Sidman) schedule (response-shock interval = 30 s) and responses on another lever produced 2 min of signaled timeout from avoidance on a variable-ratio 15 schedule. Following extended training (106 to 363 2-hr sessions), two experiments were conducted. In Experiment 1 two different methods of extinction were compared. In one session, all shocks were omitted, and there was some weakening of avoidance but little change in timeout responding. In another session, responding on the timeout lever was ineffective, and under these conditions timeout responding showed rapid extinction. The within-session patterns produced by extinction manipulations were different than the effects of drugs such as morphine, which also reduces timeout responding. In Experiment 2 shock was omitted for many consecutive sessions. Response rates on the avoidance lever declined relatively rapidly, with noticeable reductions within 5 to 10 sessions. Extinction of the timeout lever response was much slower than extinction of avoidance in all 4 rats, and 2 rats continued responding at baseline levels for more than 20 extinction sessions. These results show that lever pressing maintained by negative reinforcement can be highly resistant to extinction. The persistence of responding on the timeout lever after avoidance extinction is not readily explained by current theories.

Animals↗

The effects of cocaine on behavior maintained by timeout from avoidance.

Rats were trained on concurrent schedules under which responses on one lever postponed shock (avoidance) and responses on the other lever produced brief (2-min) periods of signaled timeout from avoidance. For 6 rats, timeout from avoidance was programmed on a variable-interval 45-s schedule that generally resulted in rates that were lower than those on the avoidance lever. For another 6 rats, timeout was arranged on a variable-ratio 15 schedule that produced higher baseline rates. Cocaine (3 to 40 mg/kg) produced large, dose-dependent increases in behavior maintained by timeout in both groups of rats. Avoidance responding was also generally increased by cocaine, but the increases were of lesser magnitude. Increases in response rates were seen across a broad range of doses on behavior maintained by either interval or ratio schedules, an outcome that was unexpected on the basis of most studies of cocaine on food-maintained behavior. These results were similar to those of previous studies of the effects of amphetamine on behavior maintained by timeout from avoidance and suggest that stimulant drugs affect behavior maintained under a shock-postponement schedule differently than they affect behavior maintained by timeout from avoidance.

Amphetamine↗

Reversal of baseline relations and stimulus equivalence: I. Adults.

Following the emergence of two four-member equivalence classes (A1B1C1D1 and A2B2C2D2), 5 students were exposed to a series of phases including a baseline conditional discrimination reversal (i.e., choosing D2 was reinforced and D1 punished given Sample A1; choosing D1 was reinforced and D2 punished given Sample A2), the delayed introduction of CD/DC transitivity/equivalence probes, DE conditional discrimination training, a second baseline conditional discrimination reversal (i.e., choosing C2 was reinforced given B1, etc.), and a return to original baseline reinforcement contingencies. Results showed that baseline and symmetry probe performances were extremely sensitive to baseline modifications. In contrast, patterns on transitivity/equivalence probes remained predominantly consistent with the originally established equivalence classes, although there were exceptions on some E probe relations for 2 subjects. The dissociation between baseline and symmetry versus transitivity/equivalence patterns may have important implications because it is not easily accounted for by current models of equivalence phenomena.

Journal Article↗

Reversal of baseline relations and stimulus equivalence: II. Children.

In a systematic replication of a study using college-student subjects (Pilgrim & Galizio, 1990), 5- to 7-year-old children learned two conditional discriminations (i.e., A1B1, A2B2, A1C1, and A2C2) in a two-choice arbitrary match-to-sample task and showed the emergence of two three-member equivalence classes (A1B1C1 and A2B2C2). Baseline conditional discrimination performance were quickly controlled by reversals of the AC reinforcement contingencies (i.e., choosing Comparison Stimulus C2 was reinforced given Sample A1, and choosing C1 was reinforced given Sample A2) when the reversals were introduced in restricted baselines. On reflexivity, symmetry, and transitivity/equivalence probes following the reversal, there was some limited indication of equivalence-class reorganization (i.e., A1B1C2 and A2B2C1) in keeping with the concurrently performed baseline relations for 2 of 5 subjects, but the predominant pattern across probe trials was one of inconsistent conditional control. These findings suggest that, given similar challenges, equivalence-class performances may be more easily disrupted in young children than in adults.

Attention↗

Variable-ratio schedules of timeout from avoidance: effects of d-amphetamine and morphine.

Rats were trained on concurrent schedules in which pressing one lever postponed shock and pressing the other lever produced periods of signaled timeout from avoidance on variable-ratio schedules. These procedures generated high rates of timeout-reinforced responding and provided a baseline for studying the effects of drugs on behavior maintained by different types of negative reinforcement (shock postponement vs. timeout). Morphine (2.5 to 10.0 mg/kg) reduced behavior maintained by timeout at doses that increased or had no effect on avoidance responding. In contrast, d-amphetamine (0.125 to 2.0 mg/kg) produced large increases in timeout responding at doses that had minimal effect on avoidance in rats trained on variable-interval and variable-ratio schedules. Thus, the event-dependent effects of morphine, observed in previous studies in which timeout responding was maintained at low rates by interval schedules, were replicated with high timeout rates maintained by variable-ratio schedules. The effects of d-amphetamine could also be described as "event dependent" because timeout responding was stimulated more than avoidance regardless of the maintenance schedule or baseline rate.

Animals↗

Variable-interval schedules of timeout from avoidance: effects of anxiolytic and antipsychotic drugs in rats.

Concurrent performances were studied in rats under conditions where responses on one lever postponed shock on a Sidman avoidance schedule and responses on another lever produced periods of signaled timeout from avoidance on a variable-interval schedule. Chlorpromazine decreased rates of responding on both the timeout and avoidance levels to about the same extent. The effects of chlordiazepoxide and CGS 9896 depended upon the event maintaining responding. Both drugs increased responding on the timeout lever at doses that concurrently decreased responding on the avoidance lever. Thus, the novel anxiolytic CGS 9896 produced effects that closely resembled those of the benzodiazepine anxiolytic, chlordiazepoxide. Like chlorpromazine, buspirone decreased both avoidance and timeout responding. Despite the documented anxiolytic properties of buspirone, its actions here were unlike those of the other anxiolytic drugs tested. Nonetheless, the differentiation between drugs obtained with the timeout from avoidance procedure indicates its utility for behavioral pharmacology.

Animals↗

Relations between baseline contingencies and equivalence probe performances.

Following the emergence of two three-member equivalence classes (A1B1C1 and A2B2C2), 5 college students were exposed to one or more changes in the reinforcement contingencies controlling baseline conditional discriminations. AC relations were either reversed (i.e., C2 was reinforced and C1 punished when A1 was the sample; C1 was reinforced and C2 punished when A2 was the sample) or arranged randomly (i.e., C2 and C1 were reinforced and punished equally often in the presence of A1 and A2). In a third condition, the original AB and AC relations were reversed. Results showed that although baseline conditional discrimination performances were under the control of reinforcement contingencies, and performances on symmetry trials varied with baseline responding for 3 of 4 subjects when contingencies were reversed, performances on transitivity probes remained consistent with the initial equivalence class. These inconsistencies between probe and baseline performances were striking because conditional discriminations are thought to be the determinants of equivalence class performance. Similarly, the contrast between performances on symmetry and transitivity probes was of theoretical interest because equivalence classes are defined by congruent patterns of responding on probe trials.

Journal Article↗

Attenuation of the biphasic effects of ethanol on avoidance extinction by RO 15-4513 in rats.

Ethanol had biphasic effects on jump-up avoidance extinction with low doses (1 g/kg) increasing, and high doses (2.5 g/kg) decreasing number of trials to extinction criterion. In Experiment 1 these doses of ethanol were studied alone, and in combination with RO 15-4513 (0.3, 3 or 6 mg/kg). The stimulation of responding produced by low ethanol doses was reversed by 3 and 6 mg/kg doses of RO 15-4513 which had intrinsic suppressive effects, but the depressed responding produced by higher ethanol doses was not attenuated by RO 15-4513. Experiment 2 analysed the interaction between ethanol and benzodiazepine antagonists RO 15-1788 and CGS 8216. RO 15-1788 did not have intrinsic action and did not interact with ethanol. CGS 8216 showed an intrinsic suppressive action much like RO 15-4513, and also reversed the stimulation produced by low dose ethanol, but not the effects of the high dose. Experiment 3 showed that the benzodiazepine agonist, chlordiazepoxide, had effects much like low dose ethanol which were reversed by CGS 8216 and RO 15-4513. The major conclusions were that RO 15-4513 and CGS 8216 possess inverse agonist properties which may cancel out the effects of alcohol under certain circumstances.

Animals↗

Variable-interval schedules of timeout from avoidance: effects of chlordiazepoxide, CGS 8216, morphine, and naltrexone.

Rats were trained on concurrent schedules in which pressing one lever postponed shock and pressing the other occasionally (variable-interval schedule) produced a 2-min timeout during which the shock-postponement schedule was suspended and its correlated stimuli were removed. These procedures provided a baseline for studying the effects of drugs on behavior maintained by different sources of negative reinforcement (shock avoidance and timeout from avoidance). Experiment 1 studied a benzodiazepine agonist, chlordiazepoxide, and antagonist, CGS 8216. Chlordiazepoxide (2.5-30 mg/kg) had little effect on avoidance responding except at higher doses, when it reduced responding. By comparison, responding on the timeout lever was increased in 5 of 6 rats. These effects were reversed by CGS 8216 (2.5-5 mg/kg) in the 2 rats tested, but CGS 8216 had no effect by itself. Experiment 2 studied an opiate agonist, morphine, and antagonist, naltrexone, with 3 rats. Morphine's (2.5-20 mg/kg) effects were opposite those of chlordiazepoxide: At doses that either increased or had no effect on avoidance responding, morphine depressed timeout responding. Naltrexone (5 mg/kg) reversed these actions but had no effect by itself.

Animals↗

Variable-interval schedules of timeout from avoidance.

Rats were trained on concurrent schedules in which pressing one lever postponed shock and pressing the other occasionally produced a 2-min timeout during which the shock-postponement schedule was suspended and its correlated stimuli were removed. Throughout, the shock-postponement schedule maintained proficient levels of avoidance. Nevertheless, in Experiment 1 responding on the timeout lever was established rapidly, was maintained at stable levels on variable-interval schedules, was extinguished by withholding timeout, was reestablished when timeout was reintroduced, and was brought under discriminative control with a multiple variable-interval extinction schedule of timeout. These results are in contrast with Verhave's (1962) conclusion that timeout is an ineffective reinforcer when presented to rats on intermittent schedules. In Experiment 2 the consequence of responding on the timeout lever was altered so that the shock-postponement schedule remained in effect even though the stimulus conditions associated with timeout were produced for 2 min. Responding extinguished, indicating that suspension of the shock-postponement schedule, not stimulus change, was the source of reinforcement. By establishing the reinforcing efficacy of timeout with standard variable-interval schedules, these experiments illustrate a procedure for studying negative reinforcement in the same way as positive reinforcement.

Journal Article↗

Variable interval schedules of timeout from avoidance: effects of ethanol, naltrexone, and CGS 8216.

Four rats were trained on concurrent schedules of shock avoidance and timeout from avoidance, where responses on one lever postponed shock and responses on another lever occasionally (VI 45 sec schedule) produced a 2-min timeout during which the avoidance schedule was suspended. These procedures maintained stable rates of responding on both levers, providing a baseline for studying the effects of drugs on behavior under different types of aversive control (shock avoidance and timeout from avoidance). In the first experiment the effects of ethanol (0.5, 1.0, 1.5, and 2.0 g/kg) and an opiate antagonist, naltrexone (1 mg/kg) were assessed alone and in combination. Ethanol produced a dose-dependent decrease in avoidance characterized by increased shock rates and decreased response rates. At the same time, however, responding on the timeout lever generally increased relative to avoidance lever rates. All of these effects were largely confined to the early parts of the 2-hr session, when blood-ethanol levels were relatively high. Naltrexone had no effect on performances and did not interact with ethanol. In a second experiment, the effects of the benzodiazepine antagonist CGS 8216 were studied alone, and in combination with ethanol. CGS 8216 (5 mg/kg) generally disrupted both avoidance and timeout responding but did not reverse ethanol actions.

Animals↗

Correlates of sensation seeking in alcoholics.

Alcoholics differentiated on the basis of their scores on the Sensation-Seeking Scale were found to differ markedly in their use of other psychoactive drugs, in the number and type of reinforcers given in the Reinforcer List, on some of their self-reported reasons for drinking, and in age. When subjects were classified on the basis of their MMPI profiles into subtypes, it was observed that there were differences in sensation seeking between different subtypes. The results suggest that sensation seeking may be a clinically important variable differentiating subgroups of alcoholics.

Adult↗

Effects of ethanol and naltrexone on free-operant avoidance behavior in rats.

Several recent studies have suggested that some effects of ethanol may be mediated by the opioid receptor systems. The present study examined the possibility of a common link between ethanol and opiates by determining whether the effects of ethanol on rat's free operant avoidance behavior could be reversed by the opiate antagonist naltrexone. In Experiment 1 ethanol produced a dose-dependent impairment of avoidance performance (characterized by a decrease in response rate and/or an increase in shock rate) in all three subjects. Naltrexone (3 mg/kg) alone suppressed avoidance rates, but failed to reverse or reduce the effects of ethanol. In contrast to the expectations of the "common-link" hypothesis, the greatest impairment of performance was observed after high doses of ethanol in combination with naltrexone. In Experiment 2 the effects of chronic naltrexone administration were examined. Since previous research has suggested that chronic treatment with opiate antagonists produces a heightened sensitivity to opiate agonists and antagonists, Experiment 2 addressed the issue of whether sensitization to naltrexone would transfer to ethanol. Although increased sensitivity to the rate-decreasing effects of naltrexone was observed, there was no evidence of heightened sensitivity to ethanol. Taken together the results provided little support for the hypothesis that the effects of ethanol on avoidance performance are mediated by the opiate receptor system.

Animals↗