WITHDRAWAL OF CHRONIC CHLORPROMAZINE MEDICATION: AN EXPERIMENTAL ANALYSIS

Approximately 50% of all institutionalized, mentally retarded adults receive psychotropic medication to control inappropriate behavior. In this study, behaviors exhibited by five retarded adults were formally observed while they were on and off medication. Each subject had been receiving chlorpromazine for six or more years prior to the start of the study. The drug was withdrawn and readministered using a double-blind B-A-B (drug-placebo-drug) design. Effects were highly individualized. Some desirable behavior emerged when chlorpromazine was discontinued.     

Effects of d-amphetamine, chlorpromazine, and chlordiazepoxide on intercurrent behavior during spaced-responding schedules.

Effects of d-amphetamine, chlorpromazine, and chlordiazepoxide on lever pressing under direct control of spaced-responding schedules were compared with effects on intercurrent drinking and wheel running in the rat. Drug effects on lever pressing were systematically related to dose and were consistent for all animals; drug effects on intercurrent behavior were generally different for each animal. In the case of lever presses, increasing doses of d-amphetamine first increased and then decreased response rate, increasing doses of chlorpromazine produced graded decreases in response rate, and doses of chlordiazepoxide up to 40 mg/kg produced no effect on response rate. These data are discussed in context with the concept of schedule control, and it is suggested that the behavioral pharmacology of intercurrent behavior be explored as a useful procedure in the experimental analysis of intercurrent behavior.     

Quantification of the effects of chlorpromazine on performance under delayed matching to sample in pigeons.

The effects of four doses of chlorpromazine (dose range 0.5 to 12.5 mg/kg) on performance under a delayed matching-to-sample procedure in pigeons was investigated, using the exponential model of memory (White, 1985). Performance was measured using a bias-free measure of discriminability, log d (Davison & Tustin, 1978), and negative exponential functions were fitted to individual-subject and group data at each dose level. A decrease in matching accuracy was found to be caused by an increase in the rate of forgetting, b, and a decrease in the initial discriminability, log d0. Changes in rate of forgetting and discriminability occurred at doses that had no statistically significant effect on response latency. The exponential model of memory accounted well for the data and provided a useful way of quantifying the effects of chlorpromazine on the processes involved in delayed matching-to-sample performance.     

Selective antagonism of the rate-decreasing effect of d-amphetamine by chlorpromazine 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. When d-amphetamine was administered alone, the overall response rate decreased and the percent errors increased with increasing doses. When a small dose of chlorpromazine, which was ineffective when given alone, was administered in combination with d-amphetamine, the rate-decreasing effect was antagonized. The antagonism was selective, however, in that the error-increasing effect of d-amphetamine was augmented by chlorpromazine. The nature of the joint effect of the two drugs thus depended on the behavioral measure: rate vs. accuracy.     

Effects of some physiological and pharmacological manipulations on shock- facilitated mouse killing by onychomys leucogaster (Northern grasshopper mouse)

Onychomys leucogaster (northern grasshopper mice) were induced to kill mice with response-contingent shock, and the effects of several physiological, pharmacological, and endocrinological variables were assessed. Lesions of the septum facilitated mouse killing, while lesions of the amygdala abolished spontaneous mouse killing and delayed shock-facilitated killing. Chlorpromazine (2.5–5 mg/kg) and chlordiazepoxide (5–10 mg/kg) facilitated mouse killing on postdrug trials but did not affect killing when the animals were drugged. Adrenalectomy, castration, and castration adrenalectomy did not alter the frequency of kill nor were sex-related differences in killing noted. These results were compared to those found by others studying the effects of lesions and drugs on mouse killing by rats.     

Effects of chlorpromazine on fixed-ratio responding: modification by fixed-interval discriminative stimuli.

Effects of chlorpromazine (1 to 100 mg/kg) were assessed on two pigeons' responding under various modifications of a multiple schedule of food delivery. During a fixed-interval component, the first response after 5 min produced food; during the subsequent, fixed-ratio component, the 30th response produced food. Modifications of the schedule entailed changes in stimulus conditions imposed during the fixed-ratio component that did not systematically alter characteristics of performance under non-drug conditions. In the first phase of the experiment, distinctive visual stimuli were correlated with each schedule component (conventional multiple schedule); chlorpromazine produced small decreases in fixed-ratio responding (20% at 30 mg/kg). When each response during the fixed-ratio component produced the stimulus correlated with the fixed-interval schedule (fixed-interval discriminative stimulus) for 1.2 s, effects of chlorpromazine were not different from those under the conventional multiple schedule. Chlorpromazine produced greater decreases in fixed-ratio responding (55% at 30 mg/kg) when either the first response of each fixed ratio changed the stimulus correlated with the fixed-ratio schedule to the fixed-interval discriminative stimulus for the remainder of the fixed-ratio component, or when the fixed-interval discriminative stimulus was presented independently of responding according to a matched temporal sequence. When the fixed-interval discriminative stimulus was present continuously during the fixed-ratio component (mixed schedule), chlorpromazine produced even more substantial decreases in fixed-ratio responding (greater than 80% at 30 mg/kg). Effects of chlorpromazine on fixed-interval responding were also modified by the schedules of fixed-interval discriminative stimulus presentation. The effects of chlorpromazine were a joint function of the stimuli prevailing during the multiple schedule and the degree to which responding influenced these stimuli.     

Effects of promazine, chlorpromazine, d-amphetamine, and pentobarbital on treadle pressing by pigeons under a signalled shock-postponement schedule.

The effects of promazine on treadle pressing to postpone the presentation of electric shock were studied in three pigeons. The effects of chlorpromazine, d-amphetamine, and pentobarbital were studied in two of these pigeons. Each treadle press postponed electric shock for 20 sec and presentation of a preshock stimulus for 14 sec. Selected doses of both promazine and chlorpromazine increased the rates of treadle pressing in all birds. The response-rate increases produced by promazine and chlorpromazine were due to increased conditional probabilities of treadle pressing both before and during the preshock stimulus. d-Amphetamine (1 and 3 mg/kg) slightly increased responding in one of the birds, but not to the extent that promazine or chlorpromazine did. In the other bird, the 10 mg/kg dose of d-amphetamine increased shock rate but did not change response rate. Some doses of d-amphetamine increased the conditional probabilities of responding both in the absence of the preshock signal and during the preshock signal in both birds. Pentobarbital only decreased response rates and increased shock rates.     

The effects of chlorpromazine and imipramine on rate and stimulus control of matching to sample.

Pigeons were trained to perform simultaneous, two-color matching to sample under a multiple fixed-ratio fixed-interval schedule of food presentation. The sequence terminating with a peck on the matching key (a "match") was treated as a unit, analogous to a single key peck in conventional schedules. Except for intermittent reinforcement of matches, no consequent stimulus distinguished matches from mismatches (sequences terminating with pecks on the nonmatching key). The pattern of matches during nondrug sessions resembled that of simpler operants maintained by similar schedules. Matches increased in rate toward the end of both components; mismatch rates increased more slowly. Imipramine increased the rate of mismatches, disrupted schedule patterning, and lowered accuracy in a dose-dependent fashion. Chlorpromazine lowered the overall rate of matches but affected schedule patterns and accuracy less than imipramine. The types of errors during drug sessions were not systematically related to the types of errors that appeared during nondrug sessions. Stimulus control was evaluated for each of the four possible color configurations and was found to be by the entire configuration of colors, not simply by the color of the sample.     

The long-term effects of naloxone,dibutyryl cyclic CMP,and chlorpromazine on aggression in mice monitored by an automated device

A device that records the squeaks of attacked mice, used in combination with a microcomputer, was evaluated as a means of monitoring fighting over extended periods. The influences of chlorpromazine, naloxone, and dibutyryl cyclic cytidine 3′5′ monophosphate were monitored for 23 hours. These drugs differed in their ability to decrease squeaking over this extended period. Naloxone, although it significantly decreased squeaking in the short-term, did not influence the 23-hour total. In contrast, dibutyryl cyclic cytidine 3′,5′ monophosphate proved to have a potent influence that resulted in a significant decrease in the total squeaking recorded over 23 hours.