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Biomedical subjects

S T Higgins

Publications and source records attributed to S T Higgins.

At least 109 records · Page 6Linked to original sources
PubMed1989

Effects of d-amphetamine on choice of social versus monetary reinforcement: a discrete-trial test.

Two mutually exclusive options were concurrently available to eight volunteers during 60-min experimental sessions. Subjects chose every three minutes between conversing with another same-sex volunteer and providing speech monologues for monetary reinforcement. d-Amphetamine (12.5 and 25 mg/70 kg) significantly increased choice of social over monetary reinforcement. Drug-produced increases in choice of the social option were associated with increases in total seconds of speech and the rate of social conversation. d-Amphetamine also increased subject ratings of effects indicative of greater sociability such as friendliness, elation and energetic. These results suggest that d-amphetamine can increase the relative reinforcing effects of social interaction.

Aged↗
PubMed1989

Dose-dependent effects of atropine on behavioral and physiologic responses in humans.

Atropine is an antimuscarinic which has been frequently studied with learning and performance tasks using both human and animal subjects. However, interpretation of data from human studies is limited by the relatively narrow range of doses used in most such studies. In the present study a wide range of atropine doses (0, 1.5, 3.0, 6.0 mg/70 kg) were given, intramuscularly, to human volunteers to assess the effects of atropine on a variety of behavioral measures, subject ratings, and physiologic function. The time course of responses was examined over 24 hours. Behavioral measures were a computerized Performance Assessment Battery (PAB) which contained measures of logical reasoning, short-term memory and rapid arithmetic, a Digit Symbol Substitution Test (DSST), and a psychomotor test of hand-eye coordination (Circular Lights). Administration of atropine produced both time- and dose-dependent effects on most measures used, although sensitivity varied across measures. At the 1.5 mg dose, no effects on performance were detected, however, after 6.0 mg reliably and 3.0 mg occasionally, impairments occurred on measures of accuracy and speed of performance. These effects generally began by 1.5 hours postdrug and returned to baseline by 7-9 hours postdrug. In contrast, certain subject ratings and physiologic variables were affected by lower doses of atropine, showing deviations from baseline at 1.5 mg and producing a time course of effects that was both earlier in onset and longer in duration than was observed with the performance measures. The present results have practical implications for the clinical utilization of atropine in situations in which optimal performance is required.

Adult↗
PubMed1989

Smoking history, instructions and the effects of nicotine: two pilot studies.

In Study 1, ten never-smokers, ten ex-smokers and nine current smokers received nicotine (2 mg) and placebo gum hourly for 4 hours on 2 consecutive days in a randomized, double-blind, cross-over protocol. Dysphoria from nicotine was greatest in never-smokers, intermediate in ex-smokers, and least in current smokers (p less than 0.05). On the third day, subjects were given concurrent access to the same gums and told to chew ad lib. Across all subjects, nicotine was an aversive stimulus (i.e., self-administered less than placebo). Nicotine was avoided most in never-smokers, intermediate in ex-smokers and least in current smokers (p less than 0.05). Study 2 used a similar protocol and compared the nine current smokers in Study 1 who were not told they would receive nicotine with eight informed smokers, i.e., smokers told they would receive nicotine. Although nicotine appeared to be a reinforcer more often in the informed smokers than in the uniformed smokers (63% vs. 22%), this result was not statistically significant. Our results suggest 1) past drug history can influence the stimulus effects of nicotine and 2) the effects of instructions on the response to nicotine may be less in experimental settings than in therapeutic settings.

Adult↗
PubMed1989

Monologue speech: effects of d-amphetamine, secobarbital and diazepam.

Drugs of abuse from different pharmacological classes increase social conversation. Alcohol and d-amphetamine also increase rates of talking in subjects producing speech monologues in an isolated context. This latter finding suggests that the increases observed during dyadic social conversation may represent general increases in talking and not specific effects on social interaction. The present study was conducted to assess whether other abused drugs also increase monologue speaking. The acute effects of secobarbital (0, 50, 150, 250 mg), d-amphetamine (0, 25 mg) (Experiment 1), and diazepam (0, 10, 20, 40 mg) (Experiment 2) were investigated in healthy, adult volunteers. Secobarbital and d-amphetamine both increased the total amount of speech emitted, while diazepam generally had no effect or decreased talking. Experiment 3 was conducted to further compare the effects of secobarbital (0, 50, 150, 250 mg) and diazepam (0, 5, 15, 25 mg) using a within-subject, crossover design. Secobarbital increased talking in three of the four subjects studied, while diazepam, again, had no effect or decreased talking. In contrast to the differences noted with talking, secobarbital and diazepam both decreased response rates in a nonverbal performance task (i.e., circular-lights procedure); they also produced many similar effects on various subject-rated measures of drug effect. Thus, the differences in the effects of these two compounds on talking are not the result of a general difference in their overall profile of behavioral effects. In summary, the results obtained with secobarbital and d-amphetamine further demonstrate that an explicitly social context is not a necessary condition to observe drug-produced increases in speech quantity. The failure of diazepam to reliably increase talking in the present study illustrates the existence of some pharmacological specificity in the effect of drugs on human speech, and suggests another way in which the behavioral effects of the barbiturates and benzodiazepines may differ.

Administration, Oral↗
PubMed1989

Effects of atropine on the repeated acquisition and performance of response sequences in humans.

The present study assessed a 24-hr time course for the acute effects of intramuscular injections of atropine sulfate (0, 1.5, 3.0, and 6.0 mg/70 kg) in healthy adult humans responding under a two-component multiple schedule of repeated acquisition and performance of response sequences. Subjects resided in an inpatient research ward for the duration of the study. In each component of the multiple schedule, subjects completed a different sequence of 10 responses in a predetermined order using three keys of a numeric keypad. In the acquisition component, the subjects' task was to acquire a new sequence each session. Eight sessions were conducted daily: one immediately before administration of the drug and then 0.5, 1.5, 3.0, 5.0, 7.0, 9.0, and 24.0 hr after administration. In the performance component, the response sequence always remained the same. Overall percentage of errors increased and overall response rates decreased in the acquisition and performance components as an orderly function of drug dose. However, these effects were selective in that behavior in the acquisition component generally was affected at lower doses than in the performance component. When behavior was affected in both the acquisition and performance components, the time courses of effects were similar. Drug effects began at 0.5 or 1.5 hr, reached peak effects between 3.0 and 5.0 hr, and returned to placebo levels between 7.0 and 9.0 hr postdrug in both schedule components. None of the drug doses produced reliable effects the day after drug administration (24-hr postdrug) in either schedule component. The present study provides the first within-subject assessment of the magnitude and duration of the effects of an anticholinergic on repeated acquisition and performance baselines and extends to atropine the selective effects on these two baselines demonstrated previously with other compounds in humans and nonhumans.

Adult↗
PubMed1989

Repeated diazepam administration: effects on the acquisition and performance of response chains in humans.

The effects of repeated diazepam administration (80 mg) were assessed across a 12-hr time course with humans responding under a two-component multiple schedule of repeated acquisition and performance of response sequences. Subjects resided in an inpatient clinical research ward for the duration of the study. In each component of the multiple schedule, subjects completed sequences of 10 responses in a predetermined order using three keys of a numeric keypad. In the acquisition component, a new response sequence was to be acquired each session. In the performance component, the response sequence always remained the same. After stable responding was obtained and the effects of the placebo assessed, diazepam was administered for 3 consecutive days. The effects of repeated diazepam administration on overall percentage of errors across the two components of the multiple schedule were selective. In the acquisition component, the first dose of diazepam increased percentage errors with the magnitude of effects decreasing across the second and third days of diazepam administration. In the performance component, the percentage of errors was either minimally affected across all 3 days of diazepam administration or substantively increased on Day 1 with subsequent diazepam administrations having minimal effects. Effects on response rate were not selective. Diazepam decreased rates of responding in both schedule components, with the magnitude of effects decreasing across successive administrations. These results replicate previous findings in humans and nonhumans on the selective effects of diazepam on acquisition versus performance baselines. Also, the results suggest that the selective effects do not result from differences in reinforcement rate. Finally, the present results demonstrate that the selective recovery from repeated drug administration previously demonstrated in nonhumans using a repeated acquisition arrangement has generality to human behavior.

Adult↗
PubMed1988

Effects of alcohol on speaking in isolated humans.

Drugs of abuse often increase human social interaction, as is suggested in our cultural drug use practices and has been demonstrated in controlled laboratory studies. The environmental and pharmacological mechanisms controlling these effects remain unclear. The present study examined the importance of a social context for obtaining drug-produced increases in human speech by examining the acute effects of alcohol (0, 22, 45, 67 g) on the amount of speech emitted by six normal volunteers who were producing speech monologues in an isolated context. A within-subject repeated-measures experimental design was used. Alcohol produced a significant dose-dependent increase in total speech. Conversely, response rates on a nonverbal behavioral task (circular-lights device) decreased as an orderly function of alcohol dose. These results suggest that a social context is not a necessary condition for alcohol to increase rates of human speech. Moreover, the decreases in response rates observed in the nonverbal task rule out the possibility that alcohol affected total speech via a generalized increase in overall activity levels.

Adult↗
PubMed1988

Time allocation in a concurrent schedule of social interaction and monetary reinforcement: effects of d-amphetamine.

Two mutually exclusive options (socializing versus monetary reinforcement) were concurrently available to two normal volunteers during 60-min experimental sessions under controlled laboratory conditions. The amount of money available in the monetary option was adjusted for individual subjects during baseline conditions until subjects divided their time approximately evenly between a social option in which they could converse with another same-sex volunteer or a monetary option in which money was earned for sitting quietly in a private room. In both subjects studied, d-amphetamine (5-25 mg) increased the percent of time allocated to the social option and total seconds of speech. This effect occurred even though increases in the time allocated to the social option necessarily resulted in a forfeiture of monetary reinforcement. The present results provide the first empirical evidence, to our knowledge, that d-amphetamine can increase the relative reinforcing effects of social interaction.

Adult↗
PubMed1988

An inverse relationship between baseline fixed-interval response rate and the effects of a tandem response requirement.

Previous experiments examining the effects of adding a tandem fixed-ratio response requirement on fixed-interval schedule performance have reported inconsistent results. One variable that may account for such inconsistencies is the baseline response rate in the fixed-interval condition. This possibility was investigated in the present study. Rats were given histories with either interresponse times greater than 11 s or fixed-ratio 40 schedules of reinforcement, which engendered either relatively low or high rates of responding, respectively, in the subsequent fixed-interval condition. A tandem ratio response requirement (fixed-ratio 9) was then introduced. The effects of adding this tandem response requirement were inversely related to the baseline fixed-interval response rates; low rates of responding in the fixed-interval condition were markedly increased, whereas high rates of responding were relatively unaffected. This inverse relationship appears to be similar to the rate-dependent relations observed in behavioral pharmacology. These results may provide an explanation for the inconsistent findings reported in previous studies on tandem fixed-interval fixed-ratio schedules and suggest that principles of behavioral pharmacology research may be applicable to the study of the effects of nonpharmacological variables on schedule-controlled behavior.

Animals↗
PubMed1987

Acute effects of ethanol and diazepam on the acquisition and performance of response sequences in humans.

The present study assessed the acute effects of p.o. administered ethanol (0, 22, 45, and 67 g) and diazepam (0, 10, 20 and 40 mg) in normal adult humans responding under a multiple schedule of acquisition and performance of 10-response sequences. In each component of the multiple schedule subjects were required to complete a different sequence of 10 responses in a predetermined order using three keys of a numeric keypad. In the acquisition component a new response sequence had to be acquired each session. In the performance component the response sequence remained the same from session to session. The higher doses of ethanol (67 g) and diazepam (20 and 40 mg) increased overall percent errors above placebo levels; the lower doses of these compounds had no significant effect. The increases in percent errors were selective across the two schedule components. Ethanol increased percent errors significantly only in the acquisition component. Diazepam increased percent errors significantly in the acquisition component at a lower dose (20 mg) than was necessary to increase errors in the performance component (40 mg). Ethanol (67 g) and diazepam (40 mg) decreased overall response rates as an orderly function of dose. In contrast to the percent errors measure, the effects on response rates were not significantly different across the performance and acquisition components. Peak effects on percent errors and response rates varied between 30 and 70 min and 45 and 80 min postdrug for ethanol and diazepam, respectively, and the duration of effects of the higher doses was greater than 3 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Acute marijuana effects on social conversation.

The present study assessed the acute effects of smoked marijuana on social conversation. Speech quantity was recorded continuously in seven moderate marijuana users during separate 1 h experimental sessions following the paced smoking of 0, 1.01, 1.84, and 2.84% THC marijuana cigarettes. Subjects engaged in conversation with undrugged partners who smoked placebo marijuana cigarettes. The active marijuana produced significant decreases in speech quantity, increases in heart rate, and increases in self-reports of "high" and sedation. Partners showed no effects in speech quantity or self-reports of drug effects that were systematically related to the doses administered to the subject pair members. The effects on speech quantity observed in the present study after acute dosing are similar to the effects on social conversation reported previously during chronic marijuana dosing. Marijuana appears to be an exception to the general rule that drugs of abuse increase verbal interaction.

Adult↗
PubMed1986

Choice of blind methadone dose increases by methadone maintenance patients.

In the present study, a choice procedure was used in an outpatient methadone maintenance clinic to examine preferences for different double-blind methadone dose increases in 5 male patients. Subjects chose between 50 mg vs. 50 mg, 60 mg, 75 mg and 100 mg of methadone. In the 50 mg vs. 50 mg condition, each alternative was selected equally often. Percent selection of the higher doses (60, 75 and 100 mg) over the 50 mg dose of methadone increased in a dose-related fashion. Subject self-reports were consistent with methadone's opiate-like properties with dose-related trends being noted in most scales (e.g. opiate effects, drug liking). Overall, the results show that a choice procedure can be used successfully to assess the reinforcing properties of drugs in methadone maintenance patients and that methadone dose increases can function as a reinforcer in this population even under blind dosing conditions.

Adult↗
PubMed1986

Contingent methadone delivery: effects on illicit-opiate use.

This study examined the effects of contingent vs. non-contingent delivery of a methadone dose supplement on relapse to illicit opiate use in the context of a methadone outpatient detoxification program. Following a 3-week methadone stabilization period on 30 mg, patients (N = 39) were randomly assigned to a contingent, a non-contingent, or a control treatment group. All patients received identical gradual reductions in their assigned methadone dose. During the dose reduction period (weeks 4-11), members of the contingent (N = 13) and non-contingent groups (N = 13) could obtain daily methadone-dose supplements up to 20 mg, but contingent group members could obtain supplements only if their most recent urinalysis results were opiate negative. Control subjects (N = 13) did not have dose increases available. The contingent group presented significantly lower opiate-positive urines during weeks 8-11 (14% positive) of the detox than the non-contingent (38% positive) or control (50% positive) groups. Additionally, the availability of extra methadone improved treatment retention and increased clinic attendance above levels observed in the control group. The potential for further use of methadone's reinforcing properties in the treatment of opiate dependence is discussed.

Adult↗
PubMed1985

Pupillary response to methadone challenge in heroin users.

The relationship between self-reported illicit heroin use and pupillary response to a low-dose methadone challenge was examined in 28 men beginning methadone therapy for opiate dependence. Pupil diameter was assessed before and 60, 90, and 120 minutes after a 20 mg methadone dose on day 1 of treatment. Self-reports of opiate drug effects were also taken at these times. There was a significant negative correlation (r = -0.53) between pupillary constriction 120 minutes after drug dosing and the average dollar value of subjects' reported heroin use per week. In other words, those who showed the least pupillary constriction generally reported the highest amount of illicit heroin use. Total years since first opiate use was also a significant predictor of pupillary response (r = -0.46). Self-reported amount of heroin use and years since first opiate use together accounted for 60% of the total variance in pupillary response to the challenge (Mult r = 0.77). Pupillary response to a low-dose methadone challenge appears to be a clinically practical and objective method for determining opiate tolerance levels in applicants for methadone therapy.

Adult↗