Biomedical subjects

J M Moerschbaecher

Publications and source records attributed to J M Moerschbaecher.

At least 55 records · Page 3Linked to original sources

PubMed1984

Effects of opioids on accuracy of a fixed-ratio discrimination in monkeys and rats.

In the presence of a stimulus above the center lever, monkeys and rats were required to complete one of two fixed-ratios (FRs) on the center lever (FR20 or FR40, monkeys; FR8 or FR16, rats). Completion of the ratio turned off the center-lever stimulus and produced a stimulus above each of the two side levers. If the completed ratio was high (e.g., FR40), a response on the left lever produced a food pellet. If the ratio was low (e.g., FR20) a response on the right lever produced food. Errors produced a brief timeout. In monkeys, d-SKF 10,047 either increased slightly or had no effect on response rate on the center lever, whereas increasing errors in a dose-related manner. In rats, both dl-SKF 10,047 and cyclazocine were found to produce a dose-related decrease in response rate and an increase in errors. The putative kappa agonist ethylketocyclazocine produced similar effects in both the monkey and rat. At doses that decreased rate of responding, accuracy was unaffected, except at the highest dose that virtually eliminated responding. Unlike any of the other drugs tested, ethylketocyclazocine decreased rate by producing a dose-related pause at the start of the session rather than by altering the local rates of responding. In monkeys, the mu agonists morphine and methadone produced dose-related decreases in response rate, primarily due to sporadic pausing. Across this same range of doses neither drug affected errors, except at the high doses in which relatively small increases obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1983

Effects of heroin, methadone, LAAM and cyclazocine on acquisition and performance of response sequences in monkeys.

In each of three components of a multiple schedule, monkeys were required to emit a different sequence of four responses in a predetermined order on four levels. Sequence completions produced food on a fixed-ratio schedule. Errors produced a brief timeout. One component of the multiple schedule was a repeated-acquisition task where the four-response sequence changed each session (learning). The second component of the multiple schedule was also a repeated-acquisition task, but acquisition was supported through the use of a stimulus fading procedure (faded learning). In a third component of the multiple schedule, the sequence of responses remained the same from session to session (performance). At high doses, each drug tested produced essentially the same effect. In all three components, response rate was substantially decreased and percent errors increased. At lower doses, however, their effects differed. Heroin and methadone produced dose-dependent sporadic periods of pausing, but had little or no effect on the accuracy of responding. LAAM also produced sporadic periods of pausing, but its effects on accuracy were variable. In contrast, cyclazocine produced no such pauses in responding but rather decreased the local rates of correct responding in a dose-related manner. These same doses of cyclazocine increased percent errors in the learning component, but not in the faded learning or performance components. The results are generally consistent with the view that putative mu opioid agonists do not affect the accuracy of a discrimination in monkeys except at those doses which produce a substantial decrease in the overall rate of responding.

Animals↗

PubMed1983

Central nervous system site of action for the respiratory depressant effect of diacetylmorphine (heroin) in the cat.

The purpose of our study was to identify central nervous system sites involved in the respiratory depressant effect of drugs that stimulate opioid receptors. Diacetylmorphine (heroin) was administered into several cerebroventricular regions of chloralose-anesthetized cats, while monitoring pulmonary ventilation with a Fleisch pneumotachograph. Administration of heroin (17, 50, 150, and 450 micrograms) into the forebrain ventricles, which was restricted to these ventricles, resulted in no significant respiratory effects. In contrast, administration of heroin into either the fourth ventricle or the cisterna magna resulted in a significant (P less than 0.05) decrease in respiratory minute volume (VE). In the fourth ventricle this was because of a decrease in frequency (f) and in the cisterna magna, to a decrease in tidal volume (VT). Intravenous administration of heroin in the same dose-range produced a decrease in VE, which was primarily due to a decrease in f. Bilateral application of heroin (70 micrograms/side) to each of three ventral medullary surface sites (Mitchell's, Schlaefke's, and Loeschcke's areas) known to influence respiration elicited a decrease in VE only at Mitchell's area. This decrease was due to decreases in f and VT. The role of this site in the action of intravenously administered heroin was tested by topical application of naloxone to this area in animals with respiratory depression evoked by intravenous heroin. Bilateral application of naloxone (15 micrograms/side) to Mitchell's area restored breathing to normal. These results lead us to suggest that the site of heroin-induced respiratory depression is a specific area (Mitchell's area) on the ventral surface of the medulla.

Administration, Topical↗

PubMed1983

Drug effects on repeated acquisition: comparison of cumulative and non-cumulative dosing.

Pigeons acquired a different four-response chain each session by responding sequentially on three keys in the presence of a sequence of four colors. The response chain was maintained by food presentation under a fixed-ratio schedule. Errors produced a brief timeout but did not reset the chain. Each day there were four 15-minute sessions, with a 10-minute inter-session interval. Cumulative dose-effect curves for phencyclidine, pentobarbital, and d-amphetamine were obtained by giving an injection before each of the four sessions; successive injections increased the cumulative dose in equally spaced logarithmic steps. For comparison, non-cumulative doses of each drug (i.e., doses not preceded by other doses on the same day) were also tested. As the cumulative dose of each drug increased, the overall response rate decreased, the percent errors increased, and there was less within-session error reduction (acquisition). With phencyclidine and pentobarbital, the rate-decreasing and error-increasing effects tended to be greater with a non-cumulative dose than with the corresponding cumulative dose. In contrast, with d-amphetamine, the effects were considerably greater with the cumulative doses. The results indicate that although the cumulative-dosing procedure saved a substantial amount of time in determining dose-effect curves, there were quantitative differences in effects between cumulative and non-cumulative doses.

Animals↗

PubMed1983

Pentobarbital causes cardiorespiratory depression by interacting with a GABAergic system at the ventral surface of the medulla.

A tonically active gamma-aminobutyric acid (GABA) system at Schlaefke's area (intermediate area) on the ventral surface of the medulla exerts control over cardiorespiratory function. This is the same site where Feldberg and Guertzenstein elicited pentobarbital-induced hypotension. To determine whether pentobarbital-induced cardiorespiratory depression is mediated by a GABAergic mechanism at this site, we applied this agent locally to the intermediate area in eight chloralose-anesthetized cats while monitoring respiratory activity, blood pressure and heart rate. Pentobarbital (0.5-1.5 mg) reduced minute ventilation from 383 +/- 19 to 227 +/- 31 ml/min (P less than .05) by reducing tidal volume from 29.8 +/- 2.4 to 16.1 +/- 1.6 ml (P less than .05), without changing respiratory rate. Mean blood pressure and heart rate were reduced from 150 +/- 16 mm Hg and 182 +/- 8 beats/min to 73 +/- 16 mm Hg and 136 +/- 12 beats/min (P less than .05), respectively. Respiratory depression culminated in apnea in each animal tested. Bicuculline applied to the intermediate area in doses that selectively counteract GABA-induced apnea (5.0-17.5 micrograms) reestablished breathing, mean arterial pressure and heart rate to values equal to or greater than control levels. This dose range of bicuculline had no effect on heroin-induced respiratory depression. Cardiorespiratory depression observed with i.v. administration of pentobarbital in four cats was also reversed by bicuculline (10-20 micrograms) applied to the intermediate area. These results indicate that pentobarbital acts at the intermediate area to activate a GABAergic system resulting in cardiorespiratory depression.

Animals↗

PubMed1983

Differential effects of prototype opioid agonists on the acquisition of conditional discriminations in monkeys.

In each of two components of a multiple schedule, patas monkeys were required to respond on a right or left lever depending upon the stimulus combination (a color and a geometric form) presented. Reinforcement of a response in the presence of one stimulus (the form) was conditional upon the other stimulus (the color). The completion of a two-member chain of discriminations produced a food pellet. Errors produced a brief time-out. One component of the multiple schedule was a repeated-acquisition task where the discriminative stimuli for left- and right-lever responses changed each session (learning). In the other component, the discriminative stimuli were the same each session (performance). Morphine, ketocyclazocine and SKF 10,047 each produced dose-related decreases in overall rate of responding in both components of the multiple schedule. However, each drug affected the patterning of responding in a different manner. Across a range of doses which decreased response rate, neither morphine nor ketocyclazocine affected accuracy of the discriminations. In contrast, SKF 10,047 and its enantiomers produced a dose-dependent disruption of accuracy; errors were increased in the acquisition component at doses lower than those required to disrupt the discrimination in the performance component. The effects of the l-isomer of SKF 10,047 were generally comparable to those of the racemate. In comparison to the racemate, the d-isomer of SKF 10,047 was found to produce greater error-increasing effects in the acquisition component and smaller rate-decreasing effects in both components of the multiple schedule. In general, the effects of cyclazocine and pentazocine on both accuracy and rate of responding were comparable to those obtained with SKF 10,047. The results suggest that in patas monkeys, opioids with activity at the putative sigma receptor such as SKF 10,047, cyclazocine and pentazocine exert a dose-dependent disruptive effect on the accuracy of discriminations, an action not shared by prototypical mu and kappa opioid agonists, at doses which produce approximately equivalent rate-decreasing effects.

Animals↗

PubMed1982

Phencyclidine in combination with pentobarbital: supra-additive effects on complex operant behavior in patas monkeys.

In one component of a multiple schedule, patas monkeys acquired a different four-response chain each session by responding sequentially on three keys in the presence of four geometric forms (learning). In the other component, the four-response chain was the same each session (performance). The response chain in each component was maintained by food presentation under a fixed-ratio schedule. Errors produced a brief timeout but did not reset the chain. When administered alone, phencyclidine and pentobarbital, at the higher doses, generally decreased the overall response rate and increased the percent errors in both components. The performance component tended to be less sensitive than the learning component to the drug effects. When phencyclidine was administered in combination with pentobarbital, the phencyclidine dose-effect curves for both rate and accuracy generally shifted progressively to the left as the dose of pentobarbital was increased. In two of three monkeys, combinations of phencyclidine with a high dose of pentobarbital consistently produced greater rate-decreasing and error-increasing effects than expected from simple addition of the effects of each drug given alone. In other words, the phencyclidine-pentobarbital combinations produced supra-additive effects on responding under the multiple schedule.

Animals↗

PubMed1982

Phencyclidine in combination with pentobarbital: supra-additive effects on complex operant behavior in pigeons.

Pigeons acquired a different four-response chain each session by responding sequentially on three keys in the presence of four colors. The response chain was maintained by food presentation under a fixed-ratio schedule. Errors produced a brief timeout but did not reset the chain. When phencyclidine was administered alone, the overall response rate decreased and the percent errors increased with increasing doses. Similar effects were found with a high dose of pentobarbital alone. When phencyclidine was administered in combination with pentobarbital, the phencyclidine dose-effect curves for rate and accuracy shifted to the left as the dose of pentobarbital was increased. Combinations of phencyclidine with a high dose of pentobarbital produced supra-additive effects; i.e., the effects on rate and accuracy were greater than expected from simple addition of the effects of each drug given alone. These results extend the generality of previous findings in patas monkeys in a similar repeated-acquisition task.

Animals↗

PubMed1982

Effects of chronic phencyclidine on fixed-ratio responding: no relation to neurotransmitter receptor binding in rat cerebral cortex.

The effects of chronic phencyclidine (3.2 mg/kg for 25 days) on responding maintained under a fixed-ratio 30 schedule of food presentation were studied in rats. Initially phencyclidine produced large decreases in the overall rate of responding. This decrease was due primarily to long pauses in responding and secondarily to a decrease in local rates of responding. Although tolerance developed to the rate-decreasing effects of phencyclidine in each subject, the extent and pattern of its development differed among the subjects. After the chronic drug regimen, the rats were sacrificed. Ligand binding to muscarinic cholinergic, opiate, adrenergic, and serotonergic receptors in cortex was then compared to that in rats which received saline with operant training, phencyclidine alone, or saline alone. Neither operant behavior alone, phencyclidine alone, nor the interaction of phencyclidine and operant behavior was found to alter binding to these receptors. These results indicate that behavioral tolerance develops to phencyclidine, but it is not accompanied by changes in binding to the receptors studied.

Animals↗

PubMed1982

Intravenous diazepam in humans: effects on acquisition and performance of response chains.

A technique based upon an individual-subject design was used to investigate the effects of intravenous diazepam on the acquisition and performance of response chains in humans. In each of two conditions subjects were required to emit a different sequence of ten responses in a predetermined order on three levers. The conditions alternated within each session under a multiple schedule. In the performance condition the sequence of responses was the same each session. The second condition was a repeated-acquisition task. In this condition subjects were required to learn a different sequence of responses each session. Diazepam produced dose-dependent decreases in the overall rate of responding in each subject under both conditions. In two of the three subjects tested, errors were increased in the learning condition at doses lower than those required to disrupt accuracy in the performance condition. In one subject, accuracy in both the learning and performance conditions was equisensitive to the disruptive effects of diazepam. These data are consistent with the effects of the benzodiazepines in analogous animal procedures. Furthermore, the data suggest that the behavioral effects of intravenous diazepam may exhibit marked variations across subjects at clinically relevant doses (5-10 mg).

Adult↗

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↗

PubMed1981

Selective antagonism of the error-increasing effect of morphine by naloxone in a repeated-acquisition task.

Pigeons acquired a different four-response chain each session by responding sequentially on three keys in the presence of four colors. The response chain was maintained by food presentation under a fixed-ratio schedule. Errors produced a brief timeout but did not reset the chain. When either morphine or naloxone was administered alone, the overall response rate decreased with increasing doses. The rate-decreasing effect was accompanied by an increase in percent errors with morphine but not with naloxone. Both effects of morphine were antagonized by doses of naloxone that were ineffective when given alone. The antagonism was selective in that naloxone (3 mg/kg) completely blocked the error-increasing effect but not the rate-decreasing effect of the higher doses of morphine. The view that naloxone is a specific narcotic antagonist was supported by the finding that naloxone failed to antagonize the rate-decreasing and error-increasing effects of d-amphetamine, pentobarbital, and phencyclidine.

Animals↗

PubMed1980

Effects of phencyclidine, pentobarbital, and d-amphetamine on the acquisition and performance of conditional discriminations in monkeys.

In each of two components of a multiple schedule, monkeys were required to respond on a right or left lever depending upon the stimulus combination (a color and a geometric form) presented. Reinforcement of a response in the presence of one stimulus (the form) was therefore conditioned upon the other stimulus (the color). The completion of a two-member chain of discriminations produced a food pellet. Errors produced a brief timeout. One composition of the multiple schedule was a repeated-acquisition task where the discriminative stimuli for left- or right-lever responses changed each session (learning). In the other component, the discriminative stimuli for left- or right-lever responses were the same each session (performance). Phencyclidine, pentobarbital, and d-amphetamine each produced dose-related decreases in the overall rate of responding in both components of the multiple schedule. At high doses each drug increased the percent errors in each component. At lower doses, however, the three drugs produced selective effects on accuracy. Errors were increased in the learning component at lower doses than those required to disrupt the discrimination in the performance component. A signal detection analysis of the data revealed that none of the drugs tested increased errors by selectively affecting either discriminability or bias.

Animals↗

PubMed1980

Effects of d-amphetamine and cocaine on strained ratio behavior in a repeated-acquisition task.

Pigeons acquired a different four-response chain each session by responding sequentially on three keys in the presence of four colors. When the fixed-ratio requirement for food presentation was five completions of the chain, d-amphetamine and cocaine disrupted the behavior. As the dose of each drug was increased, the overall response rate decreased, the overall accuracy was impaired (i,e., percent errors increased), and there was less within-session error reduction (acquisition). In contrast, when the fixed-ratio requirement was either 20 or 50 completions of the chain, certain doses of both drugs produced large increases in the overall response rate by eliminating the extended pausing (ratio strain) that was characteristic of the control sessions. These rate-increasing effects were accompanied by error-decreasing effects, both during acquisition and after the response chain had been acquired. Taken together, the results show that the effects of d-amphetamine and cocaine on behavior in a repeated-acquisition task can be modulated by manipulating the value of the fixed-ratio schedule maintaining the behavior.

Animals↗

PubMed1980

Effects of d-amphetamine, cocaine, and phencyclidine on the acquisition of response sequences with and without stimulus fading.

In each of three components of a multiple schedule, monkeys were required to emit a different sequence of four responses in a predetermined order on four levers. Sequence completions produced food on a fixed-ratio schedule. Errors produced a brief timeout. One component of the multiple schedule was a repeated-acquisition task where the four-response sequence changed each session (learning). The second component of the multiple schedule was also a repeated-acquisition task, but acquisition was supported through the use of a stimulus-fading procedure (faded learning). In a third component of the multiple schedule, the sequence of responses remained the same from session to session (performance). At higher doses, d-amphetamine, cocaine, and phencyclidine decreased the overall rate of responding and increased the percent errors in all three components. At lower doses, however, the three drugs produced selective effects on errors. Errors were increased in the learning component at lower doses than those required to disrupt the behavior in the faded-learning component. The performance component tended to be the least sensitive to disruptive drug effects. The data are consistent with the view that stimulus fading can modulate the effects of drugs on acquisition.

Animals↗

PubMed1979

Effects of cocaine and d-amphetamine on the repeated acquisition and performance of conditional discriminations.

The acute and chronic effects of cocaine and d-amphetamine on food-reinforced behavior were investigated in pigeons responding on a two-component multiple schedule. In one component, the behavioral task consisted of the same chain of conditional discriminations each session (performance). In the other component, the chain of conditional discriminations was changed from session to session (learning). In comparison to control sessions, both acute cocaine and d-amphetamine increased errors in each component of the multiple schedule. Responding in the learning component, however, was generally disrupted at lower doses than those that affected responding in the performance component. At high doses, both drugs produced pauses in responding in each component in three of the four subjects. Pausing engendered by d-amphetamine was approximately twice as long as that under cocaine. Upon chronic administration, both the pausing and error-increasing effects of each drug diminished. Drug-induced changes in timeout responding, however, did not decrease during chronic administration. Redeterminations of the d-amphetamine dose-effect curves following chronic cocaine administration suggested the existence of cross-tolerance between cocaine and d-amphetamine. Both the acute and chronic data are consistent with the view that conditions of stimulus control may modulate the behavioral effects of drugs.

Animals↗

PubMed1979

Effects of methamphetamine and scopolamine on variability of response location.

Methamphetamine and scopolamine were studied in monkeys responding under a multiple fixed-ratio fixed-interval schedule of reinforcement. A response on any one of six levers could satisfy the schedule requirements. Variability of response location was evaluated in terms of switches, where a switch was defined as a response on one lever followed by a response on a different lever. Under baseline conditions the fixed-ratio schedule generated a high rate of responding and a low level of variability, while the fixed-interval schedule generated a low rate of responding and a high level of variability. Both methamphetamine (0.1 to 0.5 mg/kg) and scopolamine (2.4 to 240 microgram/kg) decreased overall response rate and increased variability of response location in each component of the multiple schedule with increasing doses of drug. At lower doses both drugs were found to decrease rate without affecting response variability.

Animals↗

PubMed1979

An experimental analysis of the effects of d-amphetamine and cocaine on the acquisition and performance of response chains in monkeys.

In one component of a multiple schedule of food presentation, monkeys acquired a different four-response chain each session by responding sequentially on three keys in the presence of four geometric forms (learning). In the other component, the four-response chain was the same each session (performance). Both d-amphetamine and cocaine, at the higher doses, disrupted the behavior in the learning component; the overall response rate decreased, the overall accuracy was impaired (i.e., percent errors increased), and there was less within-session error reduction. The performance component was generally less sensitive than the learning component to the disruptive effects of both drugs on rate and accuracy. After pre-feeding or during an extended session, the response rate decreased in both components, but accuracy was generally unaffected. When the four discriminative stimuli in both components were removed, the behavior was disrupted to a greater extent in the performance component. The disruptive effects of both drugs on behavior in the learning component were attenuated when the drugs were administered during the session after the response chain had been acquired. It was concluded that the greater sensitivity of the learning component to disruptive drug effects is related to the relatively weak stimulus control and/or the lower rate of reinforcement associated with that component.

Animals↗