Response-contingent injections of opioids have been shown to control behavior in various species.... more Response-contingent injections of opioids have been shown to control behavior in various species. To determine whether s.c. injections of etonitazene (ETZ) could maintain behavior in rats when administered under a single fixed-interval schedule. Rats were trained to lever press for eight 45-mg food pellets under a single fixed-interval (FI) 10-min schedule of reinforcement: following passage of the 10-min interval, each lever press resulted in a pellet delivery until eight pellets were obtained. Delivery of the reinforcer was signaled by a change in visual stimulus conditions. Once stable responding for the food pellets under the FI 10-min schedule was established, a s.c. injection of 3.2 micrograms/kg ETZ was administered to the rat by the investigator following schedule completion and delivery of the food pellets. After receiving the drug injection, rats were returned to the experimental chamber for 30 min and exposed to the same stimulus conditions that accompanied food reinforcement. Across sessions, the number of food pellets was decreased until rats were responding solely for the drug. Responding for the s.c. administered drug stabilized and persisted across sessions. When saline vehicle injections were substituted for the drug injections, responses diminished across sessions to levels below that of the drug baseline. Subsequent alternating blocks of ETZ and vehicle injections produced respective increases and decreases in responding. This study demonstrates that response-contingent s.c. injections of a drug can control behavior in rats, systematically replicating a previous experiment that used the i.p. route. Since all pertinent operant behavior is emitted prior to the administration of drug, this procedure can be used for testing the reinforcing effects of a drug without interference from any direct (rate-altering) drug effects. The present findings also extend the conditions under which drugs of abuse may reinforce behavior.
Journal of Pharmacology and Experimental Therapeutics, Jun 1, 1981
Methods Animals. Twenty-five naive male Wistar rats (Bio-Lab, St. Paul, MN) weighing between 375 ... more Methods Animals. Twenty-five naive male Wistar rats (Bio-Lab, St. Paul, MN) weighing between 375 to 465 g were used in these experiments. Separate groups of naive rats were used for each drug tested. Before the beginning of the experiment, the rats were housed in ...
Methadone usually is taken orally for drug abuse treatment in humans but oral methadone self-admi... more Methadone usually is taken orally for drug abuse treatment in humans but oral methadone self-administration by laboratory animals has not been investigated extensively. The present study examines acquisition and maintenance of oral methadone maintained responding in four adult male rhesus monkeys. Drug solution was available from one liquid delivery system and water from a second system during daily 3-h sessions. Locations of liquids were reversed each session, and liquid (0.65 ml per delivery) was delivered according to a fixed-ratio reinforcement schedule. Initially a test for the reinforcing effects of 0.00625-0.4 mg/ml methadone solutions was carried out but a consistent preference for drug over water was not seen. To establish methadone as a reinforcer, a fading procedure was used in which responding was first maintained by solutions of methadone (0.00625-0.4 mg/ml) combined with ethanol (0.0325-2.0% w/v). Subsequently, the concentration of the ethanol in the combination was gradually reduced to zero. Methadone-maintained responding (0.4 mg/ml) persisted when ethanol was no longer present. To confirm that the drug was serving as a reinforcer, the dose was varied: (a) by changing the volume delivered while the concentration was held constant and (b) by changing the concentration of the methadone while the volume per delivery was held constant. Over a wide range of doses, deliveries of methadone solution usually exceeded deliveries of concurrently available water. Orderly relationships were observed among methadone dose, response rate, and drug intake. The study of oral self-administration of opioid drugs by nonhuman primates may be a useful strategy for the development and evaluation of new drug substitution or replacement therapies.
Recent developments in alcoholism: an official publication of the American Medical Society on Alcoholism, the Research Society on Alcoholism, and the National Council on Alcoholism
Alcohol and other drugs are compared with respect to their abuse liability and dependence potenti... more Alcohol and other drugs are compared with respect to their abuse liability and dependence potential. Drug-reinforced behavior is defined, and factors related to the establishment of this behavior that have received increasing experimental attention in recent years are reviewed. Acquisition techniques, schedule of access, route of self-administration, and organism factors, such as species, gender, and genetic background, are discussed. Other areas of emerging interest are the effect of feeding regimens, alternative reinforcers, and social conditions on drug-reinforced behavior. Also, biochemical factors such as neurochemical alterations, hormonal changes, and alcohol and other drug combinations, are considered. Finally, dependence potential is considered in terms of observational changes and performance alterations that seem to be sensitive indicators of the protracted aspects of drug withdrawal. The relationship between drug-seeking behavior and withdrawal is examined.
The relationship between drug concentration and choice. PHARMACOL BIOCHEM BEHAV 54(3) [547][548][... more The relationship between drug concentration and choice. PHARMACOL BIOCHEM BEHAV 54(3) [547][548][549][550][551][552][553][554] 1996.-The relative reinforcing effects of orally delivered methadone were studied in five male rhesus monkeys. Drug deliveries were available under either a fixed-ratio (FR) or a fixed-interval (FI) schedule. Three concentrations of methadone, low (0.05 mg/ml), intermediate (0.2 mg/ml), and high (0.8 mg/ml) were delivered in 0.65 ml volumes. In the first experiment, monkeys were presented with a choice paradigm. Under independent FR schedules responding led to a delivery of either a methadone solution or the water vehicle. For each concentration, deliveries of a methadone solution maintained higher response rates than did deliveries of water. In the second experiment, methadone concentrations were tested in pairs in the following sequence: high vs. low, high vs. intermediate, intermediate vs. low, high vs. intermediate (retest), and high vs. low (retest). The retest of the last two pairs was designed to counterbalance the test sequence, so that order effects, if they existed, could be detected. Regardless of the schedule, the higher concentration of the methadone pair maintained a greater response rate than did the lower concentration. The present results are consistent with the generalization based on other studies that over a broad range of concentrations and across pharmacological classes, reinforcement schedules, and routes of administration, reinforcing effects increase with increases in drug concentration. Drug self-administration Methadone Opioids Drug addiction Reinforcement magnitude Drug reinforcement Choice Dose Relative reinforcement Fixed-ratio schedules Choice procedures Oral route Rhesus monkeys IN DRUG self-administration studies with simple reinforcement schedules response rate is usually an inverted U-shaped (or bitonic) function of dose . This response-rate function has been interpreted several ways. The ascending part of the curve often has been ascribed to increases in reinforcing effects with increases in dose, while the descending portion has been attributed to motor impairment, satiation, aversive effects, and/or decreases in reinforcing effects (15). If decreases in response rate do reflect decreases in reinforcing effectiveness, then the dose that maintains the highest rate of responding, that is, the dose at the peak of the inverted U-shaped function should be the most reinforcing dose, and rate of responding would be a universal measure of the magnitude of reinforcing effects. However, this interpretation has not been' supported by studies with rhesus monkeys (13,14,17,18, 21,22,37). These studies were conducted with psychomotor stimulants and barbiturates as reinforcers, and indicate that, at least with these drugs, the dose that maintains the highest rate is usually not the most reinforcing dose.
Journal of Pharmacology and Experimental Therapeutics
Studies of ethanol drinking suggest an inverse correlation between innate sensitivity to ethanol ... more Studies of ethanol drinking suggest an inverse correlation between innate sensitivity to ethanol and behavior reinforced by this drug. The present study investigated ethanol reinforced behavior in mice selectively bred for high, Long Sleep/Institute for Behavioral Genetics (LS), and low, Short Sleep/Institute for Behavioral Genetics (SS), sensitivity to ethanol. Results show that both lines will drink large amounts of ethanol postprandially. However, in the absence of food presentation, LS and SS mice differed significantly in ethanol reinforced behavior. Ethanol maintained higher rates of responding, greater intake and higher blood ethanol levels in LS relative to SS mice across increasing fixed-ratio values. Ethanol did not maintain fixed-ratio lever pressing above rates maintained by vehicle in SS mice. Responding for and consumption of 8% ethanol significantly exceeded that of vehicle only in LS mice. Response rates of LS mice showed a typical inverted U-shaped relationship to ethanol concentration. Postsession blood ethanol levels and body temperatures indicated pharmacologically significant ethanol intake only in LS mice. Thus, ethanol served as an effective reinforcer in LS mice across a range of environmental conditions. Conversely, ethanol was not established as a positive reinforcer in SS mice under any of the broad range of conditions studied. These results are not consistent with the frequently reported negative correlation between ethanol intake and sensitivity to ethanol and rule out a causal basis for correlations seen between these traits.
The effects of response requirement and small doses of methadone on human oral self-administratio... more The effects of response requirement and small doses of methadone on human oral self-administration of methadone were examined. Three methadone maintenance patients stabilized at a dose of 80mg methadone per day were recruited as subjects. Completing a response requirement, fixed ratio (FR) of 32, 64 or 128 responses (FR32, FR64, FR128) on one button dispensed 10ml of drug solution. Completing the equivalent response requirement on a second concurrently available response button dispensed 10ml of vehicle. The opportunity to respond was unavailable until the drug or vehicle had been consumed. Each 10ml of drug solution contained methadone doses of 0.027, 0.054 or 0.108mg/ml. The frequency of deliveries was limited so that subjects could not ingest more than 54mg of methadone; the difference between the 80mg daily methadone dose and the methadone consumed in session was administered 30min post-session. At FR64 and FR128 the frequency of deliveries decreased, at the 0.054 and 0.027mg/ml doses, relative to the frequency of deliveries at FR32. The amount of methadone consumed increased with increases in methadone dose and decreased with increases in FR size. These results demonstrate the reinforcing effects of small unit doses of methadone. This procedure provides a sensitive baseline for examining effects of other pharmacological interventions on methadone ingestion in humans.
The present study examined whether in humans the generalized matching law described the relation ... more The present study examined whether in humans the generalized matching law described the relation between relative responding and relative drug intake by humans under concurrent variable interval variable interval (conc VI VI) schedules of drug reinforcement. Methadone-maintained patients, stabilized on 80 mg per day of methadone, were recruited and trained to button press for repeated deliveries of small volumes (10 ml) of 0.08 mg/ml methadone solution. In the training phase, deliveries of methadone or vehicle solution were arranged under conc VI VI schedules of reinforcement. The mean interval for the methadone and for the vehicle options was 60 , 90, 120, 180, and 240 s. During another phase, responding on either of 2 buttons produced methadone solution. For the comparison option , the mean interval was 60, 90, 120, 180 or 240 s. For the concurrently available standard option, the mean interval was a constant 120 s. When methadone and vehicle were available, methadone was preferred to vehicle . When methadone was available at either option , the generalized matching law described the relation between relative response allocation and methadone intake. The results extend the generality of the matching law to human drug self-administration. The study also demonstrated the importance of reinforcement context as a determinant of human behavioral allocation.
ABSTRACT Examines psychological dependence on benzodiazepines (BZs), and presents findings from B... more ABSTRACT Examines psychological dependence on benzodiazepines (BZs), and presents findings from BZ self-administration (SA) research in animal and humans Ss. SA, reinforcement, and addiction are defined and contrasted. Effects of different BZs are described, indicating that most BZs are capable of reinforcing drug-taking behavior. BZ reinforcement appears to be a general effect of drugs acting as agonists at the BZ receptor. BZs appear to have a moderate abuse/addiction potential, less than barbiturates but more than some other non-BZ alternatives. Persons most at risk for BZ addiction appear to be those with a history of sedative and alcohol abuse. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
The Journal of pharmacology and experimental therapeutics, 1994
Oral benzodiazepine self-administration was examined in four adult male rhesus monkeys with histo... more Oral benzodiazepine self-administration was examined in four adult male rhesus monkeys with histories of ethanol- and pentobarbital-reinforced behavior. Drug solutions and vehicle were concurrently available for 3-hr each day under fixed-ratio (FR) reinforcement schedules. Initially, the monkeys rejected a midazolam solution (0.1 mg/ml) after direct substitution of the drug for an 8% ethanol solution. However, midazolam self-administration was subsequently established by using a fading procedure in which increasing amounts of drug (0.0125-0.2 mg/ml) were gradually added to an 8% ethanol solution, followed by gradual reduction of the ethanol concentration to zero. Midazolam was an effective reinforcer for three of four monkeys tested, i.e., responding that was maintained by the drug solution exceeded that maintained by the drug vehicle. The fourth monkey also self-administered midazolam but drug-maintained responding was not consistently greater than vehicle-maintained responding. Th...
1. In Lewis (LEW), Fischer 344 (F344), Spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) ra... more 1. In Lewis (LEW), Fischer 344 (F344), Spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats, pentobarbital (PB)-induced sleep time was much longer in female than in male rats. 2. At the time of awakening, brain levels of PB were significantly higher in the female F344 than in the male rats, but there was no sex differences in other strains. 3. Each strain of rats was treated with PB-admixed food for 47 days. There were significant sex differences in mean drug intake of the SHR and LEW strains, but not the WKY and F344 strains during the final concentration. 4. Only female rats exhibited moderate to severe motor impairment by PB. 5. After PB treatment ended, various signs of PB withdrawal occurred in female, but not male, rats. These marked sex differences were observed in all four inbred strains. 6. The sex differences in physical dependence on PB may be due mainly to differences in rates of drug metabolism for the LEW, SHR and WKY rats, and to differences in CNS sensitivity...
... Also, high impulsivity predicted escalation and reinstatement of cocaine-seeking behav-ior, b... more ... Also, high impulsivity predicted escalation and reinstatement of cocaine-seeking behav-ior, but LoI rats ... In contrast, when free-choice novelty procedures were used (96), there were nega ... Other genetically divergent lines show differences in drug SA (eg, Lewis > Fischer 344), but ...
Rats given continuous access to etonitazene hydrochloride in their drinking water (5 micrograms p... more Rats given continuous access to etonitazene hydrochloride in their drinking water (5 micrograms per milliliter) more than doubled their drug intake while deprived of food. Another group of rats with implanted jugular catheters self-administered etonitazene (10 micrograms per kilogram) intravenously on a continuous reinforcement schedule, and the number of infusions increased significantly on days when they were deprived of food. These results suggest that feeding condition may be a powerful determinant of drug-reinforced behavior.
Response-contingent injections of opioids have been shown to control behavior in various species.... more Response-contingent injections of opioids have been shown to control behavior in various species. To determine whether s.c. injections of etonitazene (ETZ) could maintain behavior in rats when administered under a single fixed-interval schedule. Rats were trained to lever press for eight 45-mg food pellets under a single fixed-interval (FI) 10-min schedule of reinforcement: following passage of the 10-min interval, each lever press resulted in a pellet delivery until eight pellets were obtained. Delivery of the reinforcer was signaled by a change in visual stimulus conditions. Once stable responding for the food pellets under the FI 10-min schedule was established, a s.c. injection of 3.2 micrograms/kg ETZ was administered to the rat by the investigator following schedule completion and delivery of the food pellets. After receiving the drug injection, rats were returned to the experimental chamber for 30 min and exposed to the same stimulus conditions that accompanied food reinforcement. Across sessions, the number of food pellets was decreased until rats were responding solely for the drug. Responding for the s.c. administered drug stabilized and persisted across sessions. When saline vehicle injections were substituted for the drug injections, responses diminished across sessions to levels below that of the drug baseline. Subsequent alternating blocks of ETZ and vehicle injections produced respective increases and decreases in responding. This study demonstrates that response-contingent s.c. injections of a drug can control behavior in rats, systematically replicating a previous experiment that used the i.p. route. Since all pertinent operant behavior is emitted prior to the administration of drug, this procedure can be used for testing the reinforcing effects of a drug without interference from any direct (rate-altering) drug effects. The present findings also extend the conditions under which drugs of abuse may reinforce behavior.
Journal of Pharmacology and Experimental Therapeutics, Jun 1, 1981
Methods Animals. Twenty-five naive male Wistar rats (Bio-Lab, St. Paul, MN) weighing between 375 ... more Methods Animals. Twenty-five naive male Wistar rats (Bio-Lab, St. Paul, MN) weighing between 375 to 465 g were used in these experiments. Separate groups of naive rats were used for each drug tested. Before the beginning of the experiment, the rats were housed in ...
Methadone usually is taken orally for drug abuse treatment in humans but oral methadone self-admi... more Methadone usually is taken orally for drug abuse treatment in humans but oral methadone self-administration by laboratory animals has not been investigated extensively. The present study examines acquisition and maintenance of oral methadone maintained responding in four adult male rhesus monkeys. Drug solution was available from one liquid delivery system and water from a second system during daily 3-h sessions. Locations of liquids were reversed each session, and liquid (0.65 ml per delivery) was delivered according to a fixed-ratio reinforcement schedule. Initially a test for the reinforcing effects of 0.00625-0.4 mg/ml methadone solutions was carried out but a consistent preference for drug over water was not seen. To establish methadone as a reinforcer, a fading procedure was used in which responding was first maintained by solutions of methadone (0.00625-0.4 mg/ml) combined with ethanol (0.0325-2.0% w/v). Subsequently, the concentration of the ethanol in the combination was gradually reduced to zero. Methadone-maintained responding (0.4 mg/ml) persisted when ethanol was no longer present. To confirm that the drug was serving as a reinforcer, the dose was varied: (a) by changing the volume delivered while the concentration was held constant and (b) by changing the concentration of the methadone while the volume per delivery was held constant. Over a wide range of doses, deliveries of methadone solution usually exceeded deliveries of concurrently available water. Orderly relationships were observed among methadone dose, response rate, and drug intake. The study of oral self-administration of opioid drugs by nonhuman primates may be a useful strategy for the development and evaluation of new drug substitution or replacement therapies.
Recent developments in alcoholism: an official publication of the American Medical Society on Alcoholism, the Research Society on Alcoholism, and the National Council on Alcoholism
Alcohol and other drugs are compared with respect to their abuse liability and dependence potenti... more Alcohol and other drugs are compared with respect to their abuse liability and dependence potential. Drug-reinforced behavior is defined, and factors related to the establishment of this behavior that have received increasing experimental attention in recent years are reviewed. Acquisition techniques, schedule of access, route of self-administration, and organism factors, such as species, gender, and genetic background, are discussed. Other areas of emerging interest are the effect of feeding regimens, alternative reinforcers, and social conditions on drug-reinforced behavior. Also, biochemical factors such as neurochemical alterations, hormonal changes, and alcohol and other drug combinations, are considered. Finally, dependence potential is considered in terms of observational changes and performance alterations that seem to be sensitive indicators of the protracted aspects of drug withdrawal. The relationship between drug-seeking behavior and withdrawal is examined.
The relationship between drug concentration and choice. PHARMACOL BIOCHEM BEHAV 54(3) [547][548][... more The relationship between drug concentration and choice. PHARMACOL BIOCHEM BEHAV 54(3) [547][548][549][550][551][552][553][554] 1996.-The relative reinforcing effects of orally delivered methadone were studied in five male rhesus monkeys. Drug deliveries were available under either a fixed-ratio (FR) or a fixed-interval (FI) schedule. Three concentrations of methadone, low (0.05 mg/ml), intermediate (0.2 mg/ml), and high (0.8 mg/ml) were delivered in 0.65 ml volumes. In the first experiment, monkeys were presented with a choice paradigm. Under independent FR schedules responding led to a delivery of either a methadone solution or the water vehicle. For each concentration, deliveries of a methadone solution maintained higher response rates than did deliveries of water. In the second experiment, methadone concentrations were tested in pairs in the following sequence: high vs. low, high vs. intermediate, intermediate vs. low, high vs. intermediate (retest), and high vs. low (retest). The retest of the last two pairs was designed to counterbalance the test sequence, so that order effects, if they existed, could be detected. Regardless of the schedule, the higher concentration of the methadone pair maintained a greater response rate than did the lower concentration. The present results are consistent with the generalization based on other studies that over a broad range of concentrations and across pharmacological classes, reinforcement schedules, and routes of administration, reinforcing effects increase with increases in drug concentration. Drug self-administration Methadone Opioids Drug addiction Reinforcement magnitude Drug reinforcement Choice Dose Relative reinforcement Fixed-ratio schedules Choice procedures Oral route Rhesus monkeys IN DRUG self-administration studies with simple reinforcement schedules response rate is usually an inverted U-shaped (or bitonic) function of dose . This response-rate function has been interpreted several ways. The ascending part of the curve often has been ascribed to increases in reinforcing effects with increases in dose, while the descending portion has been attributed to motor impairment, satiation, aversive effects, and/or decreases in reinforcing effects (15). If decreases in response rate do reflect decreases in reinforcing effectiveness, then the dose that maintains the highest rate of responding, that is, the dose at the peak of the inverted U-shaped function should be the most reinforcing dose, and rate of responding would be a universal measure of the magnitude of reinforcing effects. However, this interpretation has not been' supported by studies with rhesus monkeys (13,14,17,18, 21,22,37). These studies were conducted with psychomotor stimulants and barbiturates as reinforcers, and indicate that, at least with these drugs, the dose that maintains the highest rate is usually not the most reinforcing dose.
Journal of Pharmacology and Experimental Therapeutics
Studies of ethanol drinking suggest an inverse correlation between innate sensitivity to ethanol ... more Studies of ethanol drinking suggest an inverse correlation between innate sensitivity to ethanol and behavior reinforced by this drug. The present study investigated ethanol reinforced behavior in mice selectively bred for high, Long Sleep/Institute for Behavioral Genetics (LS), and low, Short Sleep/Institute for Behavioral Genetics (SS), sensitivity to ethanol. Results show that both lines will drink large amounts of ethanol postprandially. However, in the absence of food presentation, LS and SS mice differed significantly in ethanol reinforced behavior. Ethanol maintained higher rates of responding, greater intake and higher blood ethanol levels in LS relative to SS mice across increasing fixed-ratio values. Ethanol did not maintain fixed-ratio lever pressing above rates maintained by vehicle in SS mice. Responding for and consumption of 8% ethanol significantly exceeded that of vehicle only in LS mice. Response rates of LS mice showed a typical inverted U-shaped relationship to ethanol concentration. Postsession blood ethanol levels and body temperatures indicated pharmacologically significant ethanol intake only in LS mice. Thus, ethanol served as an effective reinforcer in LS mice across a range of environmental conditions. Conversely, ethanol was not established as a positive reinforcer in SS mice under any of the broad range of conditions studied. These results are not consistent with the frequently reported negative correlation between ethanol intake and sensitivity to ethanol and rule out a causal basis for correlations seen between these traits.
The effects of response requirement and small doses of methadone on human oral self-administratio... more The effects of response requirement and small doses of methadone on human oral self-administration of methadone were examined. Three methadone maintenance patients stabilized at a dose of 80mg methadone per day were recruited as subjects. Completing a response requirement, fixed ratio (FR) of 32, 64 or 128 responses (FR32, FR64, FR128) on one button dispensed 10ml of drug solution. Completing the equivalent response requirement on a second concurrently available response button dispensed 10ml of vehicle. The opportunity to respond was unavailable until the drug or vehicle had been consumed. Each 10ml of drug solution contained methadone doses of 0.027, 0.054 or 0.108mg/ml. The frequency of deliveries was limited so that subjects could not ingest more than 54mg of methadone; the difference between the 80mg daily methadone dose and the methadone consumed in session was administered 30min post-session. At FR64 and FR128 the frequency of deliveries decreased, at the 0.054 and 0.027mg/ml doses, relative to the frequency of deliveries at FR32. The amount of methadone consumed increased with increases in methadone dose and decreased with increases in FR size. These results demonstrate the reinforcing effects of small unit doses of methadone. This procedure provides a sensitive baseline for examining effects of other pharmacological interventions on methadone ingestion in humans.
The present study examined whether in humans the generalized matching law described the relation ... more The present study examined whether in humans the generalized matching law described the relation between relative responding and relative drug intake by humans under concurrent variable interval variable interval (conc VI VI) schedules of drug reinforcement. Methadone-maintained patients, stabilized on 80 mg per day of methadone, were recruited and trained to button press for repeated deliveries of small volumes (10 ml) of 0.08 mg/ml methadone solution. In the training phase, deliveries of methadone or vehicle solution were arranged under conc VI VI schedules of reinforcement. The mean interval for the methadone and for the vehicle options was 60 , 90, 120, 180, and 240 s. During another phase, responding on either of 2 buttons produced methadone solution. For the comparison option , the mean interval was 60, 90, 120, 180 or 240 s. For the concurrently available standard option, the mean interval was a constant 120 s. When methadone and vehicle were available, methadone was preferred to vehicle . When methadone was available at either option , the generalized matching law described the relation between relative response allocation and methadone intake. The results extend the generality of the matching law to human drug self-administration. The study also demonstrated the importance of reinforcement context as a determinant of human behavioral allocation.
ABSTRACT Examines psychological dependence on benzodiazepines (BZs), and presents findings from B... more ABSTRACT Examines psychological dependence on benzodiazepines (BZs), and presents findings from BZ self-administration (SA) research in animal and humans Ss. SA, reinforcement, and addiction are defined and contrasted. Effects of different BZs are described, indicating that most BZs are capable of reinforcing drug-taking behavior. BZ reinforcement appears to be a general effect of drugs acting as agonists at the BZ receptor. BZs appear to have a moderate abuse/addiction potential, less than barbiturates but more than some other non-BZ alternatives. Persons most at risk for BZ addiction appear to be those with a history of sedative and alcohol abuse. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
The Journal of pharmacology and experimental therapeutics, 1994
Oral benzodiazepine self-administration was examined in four adult male rhesus monkeys with histo... more Oral benzodiazepine self-administration was examined in four adult male rhesus monkeys with histories of ethanol- and pentobarbital-reinforced behavior. Drug solutions and vehicle were concurrently available for 3-hr each day under fixed-ratio (FR) reinforcement schedules. Initially, the monkeys rejected a midazolam solution (0.1 mg/ml) after direct substitution of the drug for an 8% ethanol solution. However, midazolam self-administration was subsequently established by using a fading procedure in which increasing amounts of drug (0.0125-0.2 mg/ml) were gradually added to an 8% ethanol solution, followed by gradual reduction of the ethanol concentration to zero. Midazolam was an effective reinforcer for three of four monkeys tested, i.e., responding that was maintained by the drug solution exceeded that maintained by the drug vehicle. The fourth monkey also self-administered midazolam but drug-maintained responding was not consistently greater than vehicle-maintained responding. Th...
1. In Lewis (LEW), Fischer 344 (F344), Spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) ra... more 1. In Lewis (LEW), Fischer 344 (F344), Spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats, pentobarbital (PB)-induced sleep time was much longer in female than in male rats. 2. At the time of awakening, brain levels of PB were significantly higher in the female F344 than in the male rats, but there was no sex differences in other strains. 3. Each strain of rats was treated with PB-admixed food for 47 days. There were significant sex differences in mean drug intake of the SHR and LEW strains, but not the WKY and F344 strains during the final concentration. 4. Only female rats exhibited moderate to severe motor impairment by PB. 5. After PB treatment ended, various signs of PB withdrawal occurred in female, but not male, rats. These marked sex differences were observed in all four inbred strains. 6. The sex differences in physical dependence on PB may be due mainly to differences in rates of drug metabolism for the LEW, SHR and WKY rats, and to differences in CNS sensitivity...
... Also, high impulsivity predicted escalation and reinstatement of cocaine-seeking behav-ior, b... more ... Also, high impulsivity predicted escalation and reinstatement of cocaine-seeking behav-ior, but LoI rats ... In contrast, when free-choice novelty procedures were used (96), there were nega ... Other genetically divergent lines show differences in drug SA (eg, Lewis > Fischer 344), but ...
Rats given continuous access to etonitazene hydrochloride in their drinking water (5 micrograms p... more Rats given continuous access to etonitazene hydrochloride in their drinking water (5 micrograms per milliliter) more than doubled their drug intake while deprived of food. Another group of rats with implanted jugular catheters self-administered etonitazene (10 micrograms per kilogram) intravenously on a continuous reinforcement schedule, and the number of infusions increased significantly on days when they were deprived of food. These results suggest that feeding condition may be a powerful determinant of drug-reinforced behavior.
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