Food and cocaine self-administration by baboons: effects of alternatives.

The effects of the availability of an alternative reinforcer on responding maintained by food pellets or drug solutions were examined in 8 adult male baboons (Papio hamadrayas anubis). During daily 23-hr experimental sessions, baboons had access to both food pellets and fluid under a two-choice procedure, in which the response requirement, under a fixed-ratio schedule, differed for the two commodities. There were no restrictions on access to water, which was continuously available from a spout at the rear of each cage. In Experiment 1, the fixed-ratio requirement, or cost, for fluid delivery remained constant while the fixed-ratio requirement for pellets was changed every 2 or 3 days when (a) no fluid, (b) a dilute dextrose vehicle, (c) 0.008 mg/kg per delivery cocaine, (d) 0.016 mg/kg per delivery cocaine, or (e) 0.032 mg/kg per delivery cocaine was available concurrently. In Experiment 1, progressively increasing the response requirement for pellets decreased pellet intake, but for 4 baboons pellet intake at maximum pellet cost was lower when cocaine, compared to the vehicle, was available. Increasing the response requirement for pellets had variable effects on vehicle intake. However, increasing the response requirement for pellets increased intake of at least one dose of cocaine to a greater extent than vehicle in all 8 baboons. Thus, cocaine could be considered a more effective economic substitute than vehicle for pellets. Experiment 2 systematically varied the order in which the response requirements for a pellet delivery were presented and added a control condition in which cocaine doses, yoked to the amount self-administered, were given three times during the session by the experimenter. Again, pellet intake at maximal pellet cost was lower when cocaine, compared to the vehicle, was available. In contrast, experimenter-given cocaine doses did not alter responding maintained by pellets. Thus, the effects of self-administered cocaine on responding maintained by food pellets differed from the effects of experimenter-given cocaine on responding maintained by food pellets.     

Modulation of Taste Aversions by a Pentobarbital Drug State: An Assessment of Its Transfer Properties

In a drug-discrimination procedure using conditioned taste aversions, a pentobarbital injection signaled a taste–toxin pairing while the vehicle injection signaled the same taste in the absence of the toxin. In transfer tests, drug states transferred control over consumption to other targets. If the training target was a fluid (saccharin), then transfer occurred to other fluids (both novel and familiar) but not to solid food. If the training target was food, then some transfer occurred to novel targets (both fluids and solid food) but not to familiar targets. Control rats revealed that the differential consumption seen during acquisition and during transfer tests was not due to the summation of two simple associations (i.e., drug–toxin and flavor–toxin) but rather reflected conditional control over consumption by the drug state.     

A pharmacological examination of the resistance-to-change hypothesis of response strength.

The effects of d-amphetamine sulfate, sodium pentobarbital, haloperidol, and cholecystokinin-octapeptide were examined within the context of Nevin's (1974, 1979) resistance-to-change hypothesis of response strength. In three experiments, rats' responding was reinforced by delivery of food under chained random-interval 30-s random-interval 30-s, multiple fixed-interval 30-s fixed-interval 120-s, or multiple random-interval 30-s random-interval 120-s schedules. Each rat received several doses of each drug and changes in response rate were measured. The resistance-to-change hypothesis predicts greater disruption of response rate relative to baseline in the initial component of the chained schedule and in the 120-s component of the multiple schedules. In the chained schedule cholecystokinin-octapeptide produced greater reductions in response rate relative to baseline in the initial component. However, no differences between components were observed with haloperidol or sodium pentobarbital, and high doses of d-amphetamine reduced response rate in the terminal component relatively more than in the initial component. In the multiple schedules either no differences were observed between components or response rate was reduced more relative to baseline in the 30-s component. The data fail to support the notion that drugs may be viewed within the same context as other response disruptors such as extinction, satiation, and the presentation of alternative reinforcement.     

Human coffee drinking: manipulation of concentration and caffeine dose.

In a residential research ward coffee drinking was studied in 9 volunteer human subjects with histories of heavy coffee drinking. A series of five experiments was undertaken to characterize adlibitum coffee consumption and to investigate the effects of manipulating coffee concentration, caffeine dose per cup, and caffeine preloads prior to coffee drinking. Manipulations were double-blind and scheduled in randomized sequences across days. When cups of coffee were freely available, coffee drinking tended to be rather regularly spaced during the day with intercup intervals becoming progressively longer throughout the day; experimental manipulations showed that this lengthening of intercup intervals was not due to accumulating caffeine levels. Number of cups of coffee consumed was an inverted U-shaped function of both coffee concentration and caffeine dose per cup; however, coffee-concentration and dose-per-cup manipulations did not produce similar effects on other measures of coffee drinking (intercup interval, time to drink a cup, within-day distribution of cups). Caffeine preload produced dose-related decreases in number of cups consumed. As a whole, these experiments provide some limited evidence for both the suppressive and the reinforcing effects of caffeine on coffee consumption. Examination of total daily coffee and caffeine intake across experiments, however, provides no evidence for precise regulation (i.e., titration) of coffee or caffeine intake.     

Effects of d-amphetamine, diazepam, and pentobarbital on the schedule-controlled pecking and locomotor activity of pigeons

Pigeons were trained on a variant of the autoshaping procedure devised by Matthews and Lerer (1987) in which a keylight stimulus ramp of increasing brightness signaled the passing of a 30-s interfood interval. This procedure generates two distinct behavioral components: key pecking and locomotor activity. The effects of three psychoactive drugs on these behavior classes were measured. d-Amphetamine had negligible effects on both types of behavior, whereas diazepam and pentobartital increased key pecking and decreased activity in a dose-dependent fashion. In Experiment 2, the possibility that drug effects were suppressed by excessively strong stimulus control exerted in Experiment 1 was tested by decreasing the discriminability of the stimulus ramp. The direction of the effects of diazepam and pentobarbital was the same as in Experiment 1 but the magnitude of the effects tended to be larger. The effects of d-amphetamine, however, remained quite small, suggesting that, under these conditions, locomotor activity and key pecking are less sensitive to d-amphetamine. In Experiments 3 and 4, key pecking was eliminated by removing the keylight. Reinforcers were presented at fixed intervals in Experiment 3 and at variable intervals in Experiment 4. The drug effects on activity observed in Experiments 1 and 2 disappeared in both Experiments 3 and 4. The results suggest that diazepam and pentobarbital affect activity indirectly by increasing key-pecking behavior, which, in turn, competitively decreases activity.     

Response suppression by visual stimuli paired with postsession d-amphetamine injections in the pigeon

Responding of pigeons, maintained under a fixed-interval 3-minute schedule of food presentation, was decreased on days that the color of the lights illuminating the food magazine was changed and d-amphetamine (1.0 mg/kg, i.m.) was injected after the session. Responding was not decreased by keylight color changes paired with postsession d-amphetamine or by postsession injections of saline. Administration of pentobarbital (3.0 to 5.6 mg/kg), but not d-amphetamine (.3 to 3.0 mg/kg), before the session increased rates of responding suppressed by drug-paired magazine lights. Responding maintained under a fixed-ratio 30-response schedule was not decreased when differently colored magazine lights were paired with a low (.3 mg/kg) postsession dose of d-amphetamine; with high (3.0 mg/kg) postsession doses, however, responding was completely suppressed after two pairings. The effects of pairing magazine stimuli with an intermediate (1.0 mg/kg) postsession dose of d-amphetamine depended upon the magnitude of prior postsession doses. After being paired with a low dose, stimuli paired with 1.0 mg/kg did not suppress responding. After being paired with a high dose, stimuli paired with 1.0 mg/kg completely suppressed responding. The suppression of food-maintained responding by stimuli paired with postsession drug administration depends upon both behavioral and pharmacological variables.     

Facilitation of human tobacco self-administration by ethanol: a behavioral analysis.

The effect of ethanol on the cigarette smoking of alcoholic subjects was studied in a residential laboratory. During daily 6-hr sessions, cigarettes were obtained either by request to the ward staff or by operation of a lever (fixed-ratio 5 or 10). In a mixed sequence across days, sessions involved ingestion of either vehicle (orange juice or vehicle plus ethanol (133.7 g). During ethanol sessions, the rate of cigarette smoking increased from 26% to 117% of vehicle levels. A series of control studies eliminated a number of potential behavorial mechanisms for the observed effect and indicated that the ethanol-induced increase in cigarette smoking occurred under a variety of experimental conditions: (1) when smoking could not occur concurrently with ethanol or vehicle consumption; (2) when subjects were not allowed to socialize; (3) when ingestion of ethanol or vehicle was scheduled for a number of consecutive days; (4) when various doses of ethanol were administered under blind conditions. In control experiments, weighing unsmoked tobacco and counting the number of puffs per cigarette indicated the effect was not due to smoking less of each cigarette. The effect was not limited to the experimental sessions alone, since total daily smoking was higher on ethanol days than vehicle days.     

Effects of d-amphetamine and pentobarbital under concurrent fixed-ratio schedules.

Pigeons were studied under a two-key concurrent fixed-ratio schedule of food presentation. During the first five sessions, the fixed-ratio requirements were 30 responses on one key (major key) and 120 responses on the other key (minor key): responding occurred almost exclusively on the major key. When the fixed-ratio requirements were then made equal at 30 responses on both keys, responding continued to predominate on the major key. The asymmetric distribution of responses persisted when the concurrent fixed-ratio fixed-ratio schedule was interrupted with periods during which the major key was associated with extinction while the other key remained associated with a fixed-ratio schedule. Additionally, in some subjects the fixed-ratio requirements were increased. These schedule modifications decreased the asymmetry in responding but did not eliminate it. d-Amphetamine decreased rates on both keys and slightly increased the asymmetric distribution of responses, while pentobarbital reversed the distribution of responses by increasing low rates and decreasing high rates. The pigeons maintained their original asymmetric distribution of responses during the 1 1/2-year-long study, despite schedule alterations and drug administrations.     

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.