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.     

Effects of D-amphetamine and ethanol on variable and repetitive key-peck sequences in pigeons

This experiment assessed the effects of d-amphetamine and ethanol on reinforced variable and repetitive key-peck sequences in pigeons. Pigeons responded on two keys under a multiple schedule of Repeat and Vary components. In the Repeat component, completion of a target sequence of right, right, left, left resulted in food. In the Vary component, 4-peck sequences differing from the previous 10 produced food. d-Amphetamine (0.1-3.0 mg/kg, i.m.) was administered in two separate phases, separated by ethanol administration (1.0-2.0 g/kg, i.g.). Under control conditions, measures of variability were high in the Vary component, and lower in the Repeat component. Following administration of the highest dose of d-amphetamine, but not ethanol, response rates decreased in both components. d-Amphetamine and ethanol tended to increase overall sequence variability in the Repeat component, and had less of an effect in the Vary component. Performance in the Repeat component during Phase 2 of d-amphetamine administration was more disrupted than during Phase 1. Measures of variability and repetition based on shifts in the relative frequency distributions of the 16 possible keypeck sequences differed from those based on the overall measure of variability, highlighting the importance of considering both molar and molecular measures when assessing the effects of drugs on reinforced variability and repetition. In addition, the shifts in the relative frequency distribution of response sequences suggest that d-amphetamine produced decrements in repeat performance by decreasing discriminative control within response sequences, whereas ethanol decreased repeat performance by decreasing discriminability between components as well as discriminative control within response sequences.     

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.     

Concurrent phencyclidine and saccharin access: presentation of an alternative reinforcer reduces drug intake.

Six monkeys self-administered orally delivered phencyclidine ("angel dust") and saccharin under concurrent fixed-ratio 16 schedules during daily three-hour sessions. Liquid deliveries were contingent upon lip-contact responses on solenoid-operated drinking spouts. Three saccharin concentrations (0.003%, 0.03% and 0.3%, wt/vol) were tested in a nonsystematic order. For each saccharin concentration, the following series of phencyclidine concentrations (mg/ml) was presented: 0.25, 0.5, 1, 0.25 (retest), 0.125, 0.0625, 0.0312, 0.25 (retest) and 0 (water with stimuli signaling phencyclidine). As the saccharin concentration increased, the number of drug deliveries decreased, and the peaks of the concentration-response functions were shifted to the right. The lowest saccharin concentration (0.003%, wt/vol) maintained responding in excess of phencyclidine levels in only one monkey. The two higher saccharin concentrations maintained behavior far in excess of phencyclidine, but saccharin deliveries decreased in some monkeys as phencyclidine concentration and intake (mg/kg) increased. The time course and patterns of phencyclidine-reinforced responding were also altered when saccharin was concurrently available. The results are discussed in terms of strategies to reduce drug-reinforced behavior, preference between different reinforcers, and measures of reinforcing efficacy.     

肝癌经皮无水酒精注射治疗存在的问题与思考

B超引导下经皮肝内肿瘤穿刺无水酒精注射是治疗原发性肝癌的一种新颖、有效、安全的方法,但存在多次B超引导穿刺、癌灶内酒精弥散不均和酒精浓度难以维持等问题,本文用哲学的方法就此进行分析,提出采用经皮穿刺导管置入术,可避免上述问题,并可实施其他治疗。     

Drug discrimination under two concurrent fixed-interval fixed-interval schedules

Pigeons were trained to discriminate 5.0 mg/kg pentobarbital from saline under a two-key concurrent fixed-interval (FI) 100-s FI 200-s schedule of food presentation, and later tinder a concurrent FI 40-s FI 80-s schedule, in which the FI component with the shorter time requirement reinforced responding on one key after drug administration (pentobarbital-biased key) and on the other key after saline administration (saline-biased key). After responding stabilized under the concurrent FI 100-s FI 200-s schedule, pigeons earned an average of 66% (after pentobarbital) to 68% (after saline) of their reinforcers for responding under the FI 100-s component of the concurrent schedule. These birds made an average of 70% of their responses on both the pentobarbital-biased key after the training dose of pentobarbital and the saline-biased key after saline. After responding stabilized under the concurrent FI 40-s FI 80-s schedule, pigeons earned an average of 67% of their reinforcers for responding under the FI 40 component after both saline and the training dose of pentobarbital. These birds made an average of 75% of their responses on the pentobarbital-biased key after the training dose of pentobarbital, but only 55% of their responses on the saline-biased key after saline. In test sessions preceded by doses of pentobarbital, chlordiazepoxide, ethanol, phencyclidine, or methamphetamine, the dose-response curves were similar under these two concurrent schedules. Pentobarbital, chlordiazepoxide, and ethanol produced dose-dependent increases in responding on the pentobarbital-biased key as the doses increased. For some birds, at the highest doses of these drugs, the dose-response curve turned over. Increasing doses of phencyclidine produced increased responding on the pentobarbital-biased key in some, but not all, birds. After methamphetamine, responding was largely confined to the saline-biased key. These data show that pigeons can perform drug discriminations under concurrent schedules in which the reinforcement frequency under the schedule components differs only by a factor of two, and that when other drugs are substituted for the training drugs they produce dose-response curves similar to the curves produced by these drugs under other concurrent interval schedules.     

QUANTIFICATION OF ETHANOL'S ANTIPUNISHMENT EFFECT IN HUMANS USING THE GENERALIZED MATCHING EQUATION

Increases in rates of punished behavior by the administration of anxiolytic drugs (called antipunishment effects) are well established in animals but not humans. The present study examined antipunishment effects of ethanol in humans using a choice procedure. The behavior of 5 participants was placed under six concurrent variable‐interval schedules of monetary reinforcement. In three of the six concurrent schedules, punishment, in the form of monetary loss, was superimposed on one alternative. Data were analyzed according to the generalized matching equation which distinguishes between bias (allocation of behavior beyond what matching to relative reinforcer densities would predict) and sensitivity to reinforcement (how well behavior tracks relative reinforcer densities). In addition, participants completed a pencil‐tapping test. Under placebo punishment conditions, all participants demonstrated low response rates and a bias against the alternative associated with punishment, despite a resultant loss of available reinforcers. Bias against the punished alternative was dose‐dependently reduced in participants shown to be most sensitive to ethanol (0.6, 1.2, and 1.8 g/kg) in measures of overall responding and on the pencil‐tapping test. No ethanol‐induced change in bias was noted when punishment was not imposed. Sensitivity to reinforcement also decreased for participants shown to be sensitive to ethanol. In addition to extending antipunishment effects to humans, these results also show that antipunishment effects can be quantified via the matching equation.     

The effects of alcohol and persuasive social pressure on human physical aggression

Intoxicated and nonintoxicated subjects were given the opportunity to administer electric shocks to a nonprovocative opponent within the context of a competitive reaction time task. Social pressure was used to persuade subjects to administer a highly noxious electric shock to the passive opponent. The social pressure manipulation significantly increased the intoxicated subjects' use of the highly noxious shock. Non-intoxicated subjects did not evidence an appreciable increase in the use of the intense shock option.     

Effects of ethanol withdrawal on muricidal behavior

When naive rats of our colony were individually housed for 1 month with free access to laboratory chow and water as drinking fluid, 6% exhibited muricidal behavior. When naive rats of the same colony were similarly housed but received ethanol 20% in water as the sole source of drinking fluid (ll.5 g ethanol/kg/day), the percentage of killer rats was the same. However, when the rats were housed in similar conditions and submitted to a 1-day ethanol withdrawal, the percentage of muricidal rats increased to 25%. Ethanol intake in the same conditions as described above did not change muricidal behavior of spontaneous killers and did not induce killing behavior in nonkiller animals. GABA-mimetic agents administered IP blocked ethanol withdrawal-induced killing behavior as well as spontaneous muricidal activity.