Matching under nonindependent variable-ratio schedules of drug reinforcement.

Response-contingent deliveries of oral pentobarbital maintained responding of 3 rhesus monkeys during daily 3-hr sessions. Deliveries of pentobarbital were arranged under nonindependent concurrent variable-ratio variable-ratio schedules. Responses to either schedule counted toward completion of both variable-ratio schedule requirements. This schedule is similar in some respects to conventional concurrent variable-interval variable-interval schedules, in which passage of time counts toward completion of the interval value on both schedules. Restricted nonindependent concurrent variable-ratio variable-ratio schedules were also studied. On that schedule, when a drug delivery was assigned to one spout, it had to be collected before responses on the opposite spout again counted toward completion of the schedule requirements. Relative reinforcer magnitude was varied by changing the drug concentration on one schedule while keeping the drug concentration constant on the other variable-ratio schedule. Under both types of concurrent variable-ratio schedules, the relative rate of responding corresponded to the relative drug intake. Unlike earlier studies of concurrent variable-interval variable-interval intravenous cocaine reinforcement, preference was proportionate to concentration, and exclusive preferences did not develop. The relationship between relative rate of responding and relative drug intake was well described by the generalized matching law.     

Effects of delta 9-THC on marijuana smoking, dose choice, and verbal report of drug liking.

The effects of delta 9-tetrahydrocannabinol content of marijuana on cigarette smoking, dose choice, and verbal report of drug "liking" by adult males living in a residential laboratory were investigated. Marijuana cigarettes were available during programmed intervals while subjects were engaged in recreational activities. The tetrahydrocannabinol content of the cigarettes remained constant each day, but was changed across days. Subjects provided written ratings of drug liking at the end of each day. In the first study, placebo or active (2.3% delta 9-tetrahydrocannabinol) marijuana cigarettes were available for 1-, 2-, or 3-day intervals at varying times of day. The number of cigarettes smoked was unrelated to tetrahydrocannabinol content, although verbal reports of drug liking were consistently higher when marijuana cigarettes containing tetrahydrocannabinol were smoked. In a second study, a choice procedure, consisting of four 3-day blocks of 2 sample days and 1 choice day, was used. On sampling days, subjects smoked cigarettes varying in tetrahydrocannabinol content (0.0, 2.0, and 3.5%, w/w); on choice days they were allowed to choose between the two previously sampled doses. The number of cigarettes was not consistently related to tetrahydrocannabinol content. Ratings of drug liking were increased when marijuana cigarettes contained tetrahydrocannabinol, but ratings of marijuana containing 2.0% and 3.5% of the compound were similar. In contrast, subjects consistently chose the 3.5% dose over either the 0.0% or 2.0% dose. Dose choice was more sensitive to tetrahydrocannabinol content than either reports of drug liking or numbers of cigarettes smoked.     

Male HIV-1 transgenic rats show reduced cocaine-maintained lever-pressing compared to F344 wildtype rats despite similar baseline locomotion

The HIV-1 transgenic (Tg) rat model is valuable for understanding HIV-associated neurocognitive disorders (HAND) and accompanying substance use and misuse. Tg and F344/NHsd wildtype (WT) rats were allowed to self-administer intrajugular cocaine. For the first 7 sessions, neither genotype self-administered cocaine (0.1 mg/kg/infusion) on a fixed ratio 1 schedule. We thus implemented a lever–cocaine “autoshaping” session followed by a series of manipulations changing dose and reinforcement schedule. Tg rats self-administered much less cocaine than WT rats throughout the study. Of 8 Tg rats, 5 modestly increased self-administration from sessions 36–50. Of those, only 3 showed a lever discrimination. Of 10 WT rats, 8 acquired robust self-administration by session 19; all WT rats self-administered cocaine by the end of the study. WT and Tg rats had similar baseline locomotor activity in the self-administration chamber suggesting that the low levels of cocaine intake in the Tg rats did not reflect a nonspecific motor impairment in this rat strain. Concomitant measurement of activity with self-administration revealed activity increases that followed increased cocaine intake. That relation held in Tg rats. Therefore, the present study provides evidence that HIV-1 Tg rats are less sensitive to the reinforcing effects of cocaine than their F344 WT counterparts.     

The Project Method of Teaching Psychology: A Rejoinder to Dr. Cason

Unlike word frequency counts—e.g., Thorndike and Lorge—or nonsense syllable norms, the total number of different words scaled in extant norms with free associations is limited, although some words were repeatedly scaled. In order to remedy this situation and broaden the word pool for future research, a new norm for 48 words was obtained by means of free associations in the present study (N = 58 men and women undergraduate students in psychology). Discrete normative free associations were procured for 10 words for the first time by the current norm. For the words previously scaled, whereas there were some noticeable differences, overall substantial consistency was observed between the present and earlier results. Further, a survey of previously available word association norms disclosed useful information and interesting trends in this field.     

Effects of mesolimbic dopamine depletion on responding maintained by cocaine and food.

The hypothesis that mesolimbic dopamine is selectively involved in cocaine reinforcement was investigated in the rat. Animals were trained under a multiple schedule in which responding was reinforced by intravenous cocaine (0.75 mg/kg/injection) or food (45-mg pellets) under fixed-ratio 15 schedule requirements in alternate 30-min components of a 2-hr daily session. Infusion of the catecholaminergic neurotoxin 6-hydroxydopamine, but not the vehicle solution, into the region of the nucleus accumbens and olfactory tubercle produced selective reductions in cocaine self-administration without significantly altering responding maintained by food within the same sessions. This effect was reproduced in intact animals by substituting saline for cocaine in the self-administration component. These results support the hypothesis that the reinforcing effects of cocaine are dependent upon mesolimbic dopamine and demonstrate that cocaine self-administration can be disrupted in animals without altering behavior maintained by a nondrug reinforcer.     

Modifying drug-reinforced behavior by altering the economic conditions of the drug and a nondrug reinforcer.

Six rhesus monkeys were trained to self-administer orally delivered phencyclidine (0.25 mg/mL) and saccharin (0.03% wt/vol) under concurrent fixed-ratio 16 schedules. In Condition 1 the fixed-ratio requirement for phencyclidine was changed from 16 to 4, 8, 16, 32, 64, 128 and 16 while the fixed-ratio requirement for saccharin deliveries remained constant at 16. In Condition 2 the fixed-ratio value for saccharin was systematically altered while the fixed-ratio requirement for phencyclidine remained at 16, and in Condition 3 the fixed-ratio requirements for both phencyclidine and saccharin were altered simultaneously. Water was then substituted for saccharin, and the series of fixed-ratio manipulations was replicated. The phencyclidine concentration was reduced to 0.125 mg/mL and Conditions 1 and 3 were repeated. When the fixed-ratio requirement for phencyclidine was increased and the fixed-ratio requirement for saccharin or water remained fixed at 16, phencyclidine deliveries decreased when saccharin (vs. water) was concurrently available. The magnitude of the decrease ranged from 20% to 90% (of the concurrent water condition) as the fixed-ratio requirement for phencyclidine increased from 4 to 128. When the fixed-ratio requirement for phencyclidine remained at 16 and the fixed-ratio requirements for concurrent saccharin or water varied between 4 and 128, phencyclidine deliveries decreased by 30% to 40% due to the concurrent availability of saccharin (vs. water). This decrease occurred only at the three lowest fixed-ratio values when saccharin intake was relatively high. When the fixed-ratio requirements for both phencyclidine and concurrent saccharin or water were varied simultaneously, phencyclidine deliveries were reduced from 20% to 45% when saccharin (vs. water) was concurrently present. There was little effect of reducing the phencyclidine concentration when the data were analyzed in terms of unit price (responses per milligram). Thus, changes in the fixed-ratio requirement or drug concentration were functionally similar, and unit price of phencyclidine was the variable that was influenced by the presence of concurrent saccharin. These data indicate that drug-reinforced behavior is substantially reduced when the environment is enriched with an alternative nondrug reinforcer. The economic context in which these substances are presented is an important determinant of drug-reinforced behavior.     

THE AVERSIVE CONTROL OF EXCESSIVE ALCOHOL CONSUMPTION BY CHRONIC ALCOHOLICS IN THE LABORATORY SETTING1

The efficacy of several methods of aversive control of excessive alcoholic drinking was investigated in a semi-naturalistic setting that permitted objective measurement of the drinking behavior of chronic alcoholics. Studies 1A and 1B compared an escape-conditioning procedure with a control procedure in which aversive electrical shocks were administered before drinking. Neither procedure effectively decreased subjects' pretreatment, baseline alcoholic drinking behavior. In Study 2, aversive response-contingent shocks effectively suppressed alcoholic drinking, but drinking subsequently returned to its former levels after withdrawal of punishment. Self-administered shock appeared to be as effective as experimenter-administered punishment for controlling drinking, even when the punishment contingency was faded out over time. Study 3 replicated the suppressant effect of punishment, and demonstrated that contingent shock was significantly more effective than yoked, noncontingent shock. A direct comparison of self- versus experimenter-administered punishment suggested a possible slight advantage for the latter.     

Behavior controlled by scheduled injections of cocaine in squirrel and rhesus monkeys.

Rates and patterns of key-press responding maintained under schedules in which responding resulted in intravenous injections of cocaine were studied in squirrel monkeys and rhesus monkeys. Each injection was followed by a 60- or 100-sec timeout period. Schedule-controlled behavior was obtained at appropriate cocaine doses in each species. Under FR 10 or FR 30 schedules, performance was characterized by high rates of responding (usually more than one response per second) in each ratio. Under FI 5-min schedules, performance was characterized by an initial pause, followed by acceleration of responding to a final rate that was maintained until the end of the interval. Under multiple fixed-ratio fixed-interval schedules, rates and patterns of responding appropriate to each schedule component were maintained. Responding seldom occurred during timeout periods under any schedule studied. At doses of cocaine above or below those that maintained characteristic schedule-controlled behavior, rates of responding were relatively low and patterns of responding were irregular. Characteristic fixed-interval responding was maintained over a wider range of cocaine doses than characteristic fixed-ratio responding. Complex patterns of responding controlled by discriminative stimuli under fixed-ratio or fixed-interval schedules can be maintained by cocaine injections in squirrel monkeys and rhesus monkeys.     

Oral self-administration of pentobarbital by rhesus monkeys: maintenance of behavior by different concurrently available volumes of drug solution.

For 4 rhesus monkeys, mouth-contact responses with either of two brass spouts were reinforced according to fixed-ratio schedules by 0.65-mL liquid deliveries during daily 3-hr sessions. Three experiments were conducted. In each experiment, independent fixed-ratio schedules were concurrently in effect at the two spouts. Following completion of each fixed ratio on a spout, a specified number of liquid deliveries were available from that spout under a continuous-reinforcement schedule. The number of such deliveries available at each spout was manipulated independently. In Experiment 1, a 1-mg/mL pentobarbital solution was simultaneously available with water (the drug vehicle) under concurrent fixed-ratio schedules of 32 responses for 3 subjects and 64 responses for the remaining subject. The number (N) of liquid deliveries that were available after completion of each fixed ratio was varied in the following order: 8, 4, 2, 1, and 8 (retest). For each subject at each condition, drug maintained more responding than water. The number of drug deliveries obtained per session was directly related to the amount of drug available per fixed ratio (i.e., to N), whereas the number of fixed ratios completed per session generally was inversely related to the value of N. In Experiment 2, fixed-ratio size was the same for each subject as in Experiment 1, but deliveries of a 1-mg/mL pentobarbital solution were available at both spouts. The number of drug deliveries available under one fixed-ratio schedule (Ns, the "standard" reinforcer amount) was held at eight, and the number of drug deliveries available under the second schedule (Nc, the "comparison" reinforcer amount) was changed across blocks of six sessions of stable responding in the following order: 1, 2, 4, 8, 4, 2, and 1. The identical series of comparison reinforcer amounts (Nc) was then tested twice more, but with the standard reinforcer (Ns) held first at four and then at two deliveries. Across the three choice series, reinforcing effects were directly related to reinforcer magnitude. In Experiment 3, deliveries of a 1-mg/mL pentobarbital solution again were available at both spouts. However, the two reinforcer amounts were held constant at N = 8 deliveries under one schedule and N = 4 deliveries under the second schedule, and fixed-ratio size was systematically varied. Across the range of fixed-ratio sizes from low to high, the degree to which behavior was better maintained by the larger of the two drug quantities was an inverted U-shaped function of fixed-ratio size.(ABSTRACT TRUNCATED AT 400 WORDS)     

Chlordiazepoxide effects on ethanol self-administration: dependence on concurrent conditions.

Experiments examined the effects of acute doses of chlordiazepoxide upon ethanol self-administration in the rat. A concurrent-schedule procedure was used that employed choice between ethanol (5%) and a second fluid (either water or a 1% sucrose solution). When ethanol and water were the available fluids, chlordiazepoxide at doses of 15 and 20 mg/kg reduced ethanol-reinforced responding and intake, with a greater reduction occurring at the 20 mg/kg dose. However, when ethanol and sucrose were concurrently available, in many rats only the 20 mg/kg dose of chlordiazepoxide reduced ethanol-reinforced responding. The differences in dose response function occurred in most animals without large changes in the baseline ethanol-reinforced responding across the two concurrent conditions. Thus the dose-effect curve relating chlordiazepoxide and ethanol self-administration can be altered, dependent upon the nature of the concurrently available reinforcers.