Repeated Diazepam Administration: Effects on the Acquisition and Performance of Response Chains in Humans

Abstract

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.

Acute behavioral effects of estazolam and triazolam in non-drug-abusing volunteers.

“…Estazolam and triazolam impaired learning, recall, and performance on the repeated acquisition procedure, digit entry and recall task, and DSST as a function of dose. These findings systematically replicate previous reports that used these measures to assess the behavioral effects of anxiolytichypnotic-sedative compounds including alprazolam (Bickel, Hughes, & Higgins, 1990;Evans, Troisi, & Griffiths, 1994;Mumford et al, 1995aMumford et al, , 1995b, abecarnil (Mumford et al, 1995a), diazepam (Bickel, Higgins, & Griffiths, 1989, Bickel et al, 1990Desjardins, Moerschbaecher, Thompson, & Thomas, 1982;Higgins, Bickel, O'Leary, & Yingling, 1987;Higgins & Stitzer, 1990), lorazepam (Roache & Griffiths, 1987;Rush et al, 1993a), pentobarbital (Kirk et al, 1990;Roache & Griffiths, 1985), temazepam (Rush et al, 1993b;Rush & Griffiths, 1996), triazolam (Bickel et al, 1990;Evans et al, 1990;Kirk et al, 1990;Rush et al, 1993aRush et al, , 1993bRush & Griffiths, 1996), secobarbital (Higgins & Stitzer, 1990), and zolpidem (Evans et al, 1990;Rush & Griffiths, 1996). Estazolam and triazolam also increased participant-rated strength of drug effect and observer-rated sedation, which is consistent with the profile of effects produced by anxiolytic-hypnotic-sedative drugs (e.g., Evans et al, 1990;Rush et al, 1993aRush et al, , 1993b This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.…”

Response Patterns and Cardiovascular Effects During Response Sequence Acquisition by Humans

“…Subjects in the current study demonstrated consistent patterns of response sequence acquisition across sessions, as evidenced by decreases in the number of incorrect responses emitted over trials. These results are consistent with the results from a number of studies (e.g., Bickel, Higgins, & Griffiths, 1989;Higgins, Woodward, & Henningfield, 1989).…”

Effects of Cocaine and Alcohol, Alone and in Combination, on Human Learning and Performance

“…This baseline permits an assessment of drug effects on responding in transition (i.e., learning) contrasted with steady-state (i.e., performance) conditions. Drug effects often differ for these two conditions (e.g., Bickel, Higgins, & Griffiths, 1989;Desjardins, Moerschbaecher, Thompson, & Thomas, 1982;Higgins, Woodward, & Henningfield, 1989), and, thus, inclusion of both conditions provides for a more comprehensive characterization of the effects of this commonly used drug combination than either condition alone. In addition, in prior studies with humans the repeated-acquisition and performance procedure has been sensitive to the acute effects of cocaine and alcohol alone, which makes it an interesting baseline on which to study the effects of these drugs in combination (e.g., Fischman, 1984;Higgins, Bickel, O'Leary, & Yingling, 1987;Higgins, Bickel, et al, 1989 All subjects were recent but occasional users of cocaine.…”