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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 93 (1987), S. 1-7 
    ISSN: 1432-2072
    Keywords: Concentration ; Concurrent fixed-ratio schedules ; Ethanol ; Lip contact response ; Oral route ; Phencyclidine ; Rhesus monkeys
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Five monkeys were trained to self-administer orally-delivered phencyclidine (0.25 mg/ml) and water under concurrent fixed-ratio 16 (FR 16) schedules during daily sessions that lasted 3 h. An 8% (w/v) ethanol solution was substituted for water and then the following series of phencyclidine concentrations was presented: 0.25, 0.5, 1, 0.03, 0.06, 0.12, 0 (water), and 0.25 mg/ml (retest). Next, the phencyclidine concentration was held constant (0.25 mg/ml), and the ethanol concentration was varied as follows: 8, 16, 32, 1, 2, 4, 0 (water), and 8% w/v (retest). Each drug concentration series was tested again with water concurrently available. At low phencyclidine concentrations the ethanol solution was preferred, but phencyclidine deliveries exceeded ethanol deliveries at higher phencyclidine concentrations. Ethanol-maintained responding was increased by the lower phencyclidine concentrations (0.03, 0.06 and 0.12 mg/ml), and it was slightly suppressed by the highest concentration (1 mg/ml). Phencyclidine was preferred to all concentrations of ethanol except 4%. Ethanol (8%) suppressed phencyclidine-maintained behavior at lower concentrations, but it had no effect at higher phencyclidine concentrations. The ethanol concentration-response functions were nearly identical whether phencyclidine (0.25 mg/ml) or water was concurrently present. Drug preferences were usually evident within the first 10 min of the session, suggesting they were based on olfaction, taste, or other immediate postingestional effects. These results show that two orally-delivered drugs may be concurrently self-administered under independently-operating FR schedules. Behavior maintained by one drug depends on the magnitude of the concurrently available, alternative reinforcing drug.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 129 (1997), S. 206-214 
    ISSN: 1432-2072
    Keywords: Key words Acquisition ; Amphetamine ; Autoshaping ; Cocaine ; Dose ; IV intake ; Rats ; Self-administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The effect of dose on the acquisition of IV amphetamine and cocaine self-administration was examined. Three unit doses of amphetamine (0.03, 0.06 and 0.12 mg/kg) and three unit doses of cocaine (0.05, 0.2 and 0.8 mg/kg) were tested in separate groups of ten (amphetamine) or 13 (cocaine) rats. Autoshaping methods were used to train rats to press a lever that resulted in drug infusion under a fixed-ratio (FR) 1 schedule. A daily 6-h autoshaping component non-contingently delivered 60 infusions according to a 60-s random time schedule with ten infusions delivered during the first half of each h. Each day autoshaping sessions were followed by a 6-h self-administration session. The criterion for acquisition was a 5-day period during which a daily mean of 100, 50 or 25 infusions for the three amphetamine doses and 400, 100 or 25 infusions were earned during the 6-h self-administration period for the three cocaine doses, respectively. As dose increased, more rats per group acquired drug self-administration and the mean number of days to meet the acquisition criterion decreased. The percentage of rats acquiring amphetamine self-administration increased with dose and ranged from 80 to 100%. Only one rat at the lowest cocaine dose met the acquisition criterion, but 100 percent of the rats at the two higher doses acquired. During the last 2 days of acquisition, mean infusions decreased and mean drug intake (mg/kg) increased as dose increased. On the last day of acquisition, the time course of infusions during the 6-h self-administration component was characterized by a steady rate of infusions per hour, and number of infusions was inversely related to dose. These findings indicate that the initial available dose of a drug is an important determinant of the rate and probability that successful acquisition will occur.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Key words Ethanol ; Food ; Monkey ; Oral ; Phencyclidine ; Progressive ratio ; Saccharin ; Self-administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The purpose of this experiment was to determine whether attenuation of ethanol consumption by naltrexone is the result of selective changes in the reinforcing effectiveness of drug and non-drug reinforcers. A range of naltrexone doses (0.1–1.0 mg/kg) was administered for 5 days, and the effects on the reinforcing effects of orally delivered 8% (w/v) ethanol, 0.25 mg/ml phencyclidine (PCP), 0.03% (w/v) saccharin and food were studied in eight rhesus monkeys. Food and liquids were available under independent and concurrent progressive-ratio (PR) schedules (ratio range 8–4096) during daily 3-h sessions. Ethanol-maintained responding was attenuated by 0.3 and 1.0 mg/kg doses of naltrexone, while saccharin-maintained responding was decreased at the 1.0 mg/kg dose. Furthermore, there was a significant linear trend that consumption of available ethanol and saccharin was attenuated dose-dependently by naltrexone. Following 5 days of naltrexone pretreatment, ethanol- and saccharin-maintained responding immediately returned to or exceeded baseline levels. Food- and PCP-maintained responding and intake were not significantly affected by any of the naltrexone doses examined. The decreased break point (BP) values for ethanol and saccharin suggest that their reinforcing effects are mediated through opioid reinforcement mechanisms. The lack of naltrexone attenuation of PCP- and food-maintained responding suggests that these reinforcers: 1) are not sensitive to naltrexone antagonism at the doses examined, 2) are mediated by non-opioid reinforcement mechanisms, and/or 3) have less intrinsic palatability.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: Key words Alternative reinforcer ; Behavioral economics ; Drug self-administration ; Elasticity ; Magnitude ; PCP ; Rhesus monkey ; Saccharin ; Unit price
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Recent studies have shown that non-drug alternative reinforcers reduce drug self-administration. A goal of the present study was to explore factors such as magnitude of the alternative reinforcer and inter-session access to the alternative to identify conditions that lead to optimal reductions in drug intake. Objectives: To evaluate the effects of increasing the volume/delivery (v/d) of saccharin on oral phencyclidine (PCP) self-administration in rhesus monkeys given continuous access to PCP and saccharin during daily sessions using a behavioral economic analysis. The effects of availability of a saccharin solution during the inter-session period on session PCP consumption in drug-experienced monkeys was also investigated. Methods: Subjects had access to PCP (0.25 mg/ml) and either water or saccharin (0.03%) from two drinking spouts under concurrent and independent fixed-ratio (FR) schedules during daily 3-h sessions. The FR requirements for both available liquids were simultaneously increased (FR4–64). The v/d of saccharin or water was increased (from 0.3 ml to 1.2 ml), while the v/d of PCP remained constant (0.6 ml). In a second experiment, subjects had access to water or saccharin and water during the inter-session period (17.5 h) under an FR1 schedule. PCP and water were available during daily 3-h sessions under concurrent FR schedules. The FR for both liquids was increased (FR16–128). Results: PCP intake was reduced at all FRs and magnitude conditions when saccharin (versus water) was concurrently available. Varying the v/d of saccharin only had a modest effect on the extent to which PCP intake was decreased at the higher FR values. Inter-session saccharin availability (versus water) reduced session PCP intake and the magnitude of this effect was also greater at the higher FR values. Conclusions: The magnitude of the saccharin delivery had an effect on PCP consumption at higher FRs, suggesting that economic factors such as high drug cost (FR) and low cost (responses/ml) of the alternative reinforcer (saccharin) interact to produce a maximum suppression of drug intake. Between-session availability of saccharin also effectively reduced drug intake, and it had a greater effect on the maintenance levels of drug self-administration when the unit price of drug was high.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 137 (1998), S. 81-89 
    ISSN: 1432-2072
    Keywords: Key words Acquisition ; Autoshaping ; Caffeine ; Cocaine ; Food deprivation ; Intravenous self-administration ; Rats ; Saccharin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The effects of dietary caffeine and the amount and palatability of food on the acquisition of cocaine (0.2 mg/kg) self-administration were examined. Using an autoshaping procedure, seven groups of 13 rats each were trained to press a lever resulting in a cocaine (0.2 mg/kg infusion under a fixed-ratio 1 (FR 1) schedule. One group had ad libitum access to caffeine- (0.2% w/w) admixed food. Three groups had access to 10 g, 20 g or ad lib food each day. Another three groups had the same three amounts of ground food with powdered saccharin (0.2% w/w) added. During daily 6-h autoshaping sessions, ten infusions were delivered each hour under a random-time 90-s schedule after a brief (15 s) extension of a retractable lever. These were followed by 6-h self-administration sessions, when the lever remained extended and cocaine infusions were available under an FR 1 schedule. The acquisition criterion was self-administration of a mean of 100 infusions over 5 days. Cocaine self-administration was accelerated in the caffeine group compared to the regular chow group. However, by 30 days nearly the same percentage of rats in the caffeine and regular food groups met the acquisition criterion. In the other six groups, as the amount of food increased, the rate of acquisition and percentage of rats per group meeting the acquisition criterion decreased. In the ad lib group, acquisition was further reduced when saccharin was added to food. In summary, dietary caffeine accelerated acquisition and a greater amount and increased palatability of food independently interfered with acquisition of cocaine self-administration in rats.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2072
    Keywords: Key words Concentration ; Concurrent schedules ; Monkey ; Oral ; Phencyclidine (PCP) ; Progressive ratio ; Self-administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: Progressive ratio (PR) schedules have become well accepted for testing the reinforcing effectiveness of drugs. This study extends the methods to concurrent PR schedules with different concentrations of orally delivered phencyclidine (PCP). Objective: The sensitivity of the procedure is tested by presenting different PCP concentrations with independently-operating PR schedules. Method: PCP self-administration was investigated in seven rhesus monkeys. Six different PCP concentrations (0.03–1.0 mg/ml) and water were randomly paired (21 pairings). Liquid delivery (24 ml) was contingent upon lip-contact responses on solenoid-operated drinking spouts; whereby, the response requirement or fixed-ratio (FR) increased (from 8 to 16, 32, 64, 128... to 4096) after each successful completion of a previous FR and subsequent liquid delivery. Monkeys self administered PCP during daily 3-h sessions, and each pair of concentrations was held constant until behavior had stabilized for at least 4 days. Results: The higher of the two PCP concentrations always maintained greater responding, PR break point (BP), or the last ratio completed, and liquid deliveries than did the lower concentration. However, the monkeys did not exclusively respond on the drinking spout that yielded the higher drug concentration. When examined across all drug pairings, the percentage of total available deliveries of the higher concentration was significantly greater than those of the lower concentration. The monkeys maximized the amount (mg) consumed for the response output. Responding, BPs and liquid deliveries maintained by 0.12 and 0.25 mg/ml PCP were significantly greater than other PCP concentrations; however, drug intake (mg) increased directly with PCP concentration. Conclusion: These results indicate that concurrent PR schedules using oral drug self-administration and a concurrent choice paradigm reliably provide an estimation of relative reinforcing strength, and behavior maintained by these schedules is sensitive to small changes in PCP concentration.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2072
    Keywords: Key words Closed economy ; Ethanol ; Food ; Monkey ; Naltrexone ; Open economy ; Phencyclidine ; Progressive ratio ; Self-administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Previous results suggested that naltrexone had opioid-selective effects on behavior reinforced by orally delivered drugs and food. The present study explores the possibility that previous results were due to presentation of the reinforcers in a closed economy (all reinforcers earned by subjects) and that naltrexone’s effect may be nonselective under conditions of an open economy (earned reinforcers supplemented by unearned). Objectives: The purpose of this experiment was to compare the effect of naltrexone on ethanol-, phencyclidine-(PCP), and food-reinforced responding under several open-economy conditions and compare them with those from a previous report using a closed economy. Methods: Ethanol (8% w/v), PCP (0.25 mg/ml), and food were available under independent, concurrent, progressive-ratio (PR) schedules with water, and side positions were alternated daily. Three naltrexone doses (0.1, 0.3, and 1.0 mg/kg) were administered in a nonsystematic order for 5 days, with the 5-day pretreatment period serving as a control. Four economic conditions were compared: data for the closed economy were taken from a recently completed experiment using the same monkeys. The open-economy condition was varied by allowing free access to 1, 2 or 3 times the amount of drug or food that was earned during session later during a post-session time-out period. Results: In an open economy, naltrexone nonselectively suppressed ethanol, PCP, and food-maintained behavior, in contrast to results in the previous study which used a closed economy, wherein naltrexone did not significantly suppress food- or PCP self-administration. As the economy for PCP, ethanol, and food became more open, the suppressant effects of naltrexone increased and, in many animals, behavioral measures decreased to zero. Conclusion: These results indicated that the economy under which drugs and food are self-administered is an important determinant of the effectiveness of naltrexone’s ability to suppress drug- and food-reinforced behavior. The results also suggest that testing medications for drug abuse using a food control condition under a closed economy can bias the results toward a conclusion of selectivity of the treatment medication for drug-reinforced behavior.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 119 (1995), S. 127-132 
    ISSN: 1432-2072
    Keywords: Cocaine base ; Crack ; Drug self-administration ; Fixed ratio ; Food deprivation ; Food satiation ; Progressive ratio ; Reinforcing efficacy ; Rhesus monkeys ; Smoking
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Studies have shown that both food deprivation and response cost have important influences on the magnitude of self-administration of a wide variety of psychoactive drugs. In an attempt to extend these findings to the smoked route of drug self-administration, the effects of food allotment and fixed-ratio (FR) value were evaluated in four male rhesus monkeys trained to smoke cocaine base. In the first phase of the experiment, monkeys were trained to self-administer smoked cocaine base under a chained progressive-ratio (PR), fixed-ratio (FR) schedule during daily experimental sessions. Monkeys were required to make 20 lever-press responses and then five inhalations on a smoking spout to obtain the first smoke delivery. The lever ratio then increased to 60, 140, 300, 620, 1260, 2540, and 4940 for each successive smoke delivery. The initial lever ratio value was reset to 20 at the beginning of each daily session. The body weights of three monkeys were determined under free-feeding conditions. Monkeys were then restricted to 100 g food and, when body weights had stabilized, the daily food allotment was increased to 150 g, approximately 210 g, or greater than 400 g (satiation). As the daily food allotment and body weight increased, the mean number of smoke deliveries decreased in two of three monkeys. In the second phase of the experiment, three monkeys were maintained under either food-satiated or food-restricted conditions. Body weights were maintained at approximately 90% of their free-feeding weights under food-restricted conditions. The cost of the drug (lever FR value) was constant within each experimental session, but was increased after 3 consecutive days of stable responding. Fixed-ratio values were increased from 128 to 256, 512, 1024, and 2048. Monkeys were required to complete the lever FR value and then to make five inhalations on the smoking spout to gain access to 1.0 mg/kg per delivery cocaine base. The mean number of smoke deliveries increased at FR 256, 512, and 1024 when monkeys were food-restricted as opposed to food-satiated. Correspondingly, the mean number of responses increased under food-restricted conditions. Responding continued to increase over a wider range of FR values, and the peak number of responses was higher under food-restricted, as opposed to food-satiated conditions. These results, using the smoking route of administration, are consistent with the hypothesis that food deprivation increases the self-administration of reinforcing drugs.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-2072
    Keywords: Behavioral economics ; Demand ; Ethanol ; Income ; Oral ; Rhesus monkeys ; Saccharin ; Self-administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Eight rhesus monkeys (Macaca mulata) were trained to self-administer orally delivered ethanol (8%) and saccharin (0.03 or 0.3% wt/vol) or water under concurrent fixed-ratio (FR) schedules. The FR requirement for saccharin was fixed at 32, while the FR for ethanol was varied (4, 8, 16, 32, 64 and 128) in a nonsystematic order to assess demand for drug. Demand was defined as consumption plotted as a function of price (FR). Income was defined as the duration of access to available resources. Income was varied by allowing access to the concurrently available liquids 20, 60 or 180 min per day. Order of testing was counter-balanced across monkeys. Saccharin deliveries were much higher than ethanol deliveries under the 180-min income condition; however, they were lower than ethanol deliveries when income was reduced to 20 min and the ethanol FR was 4, 8 or 16. Thus, when the price of drug was relatively low, consumption of drug exceeded that of the nondrug reinforcer, and that relationship was reversed as income decreased. Saccharin deliveries sustained a proportionally greater reduction due to decreased income compared to ethanol deliveries. As income decreased from 180 to 20 min, saccharin deliveries were reduced by an average of 79.1% (across ethanol FR conditions) while ethanol deliveries were reduced by an average of 41.2 and 40.8% when concurrent saccharin or water were available, respectively; thus, drug self-administration was more resistant to income changes than saccharin. The demand for ethanol was shifted downward in a parallel fashion as income decreased. As ethanol cost (FR) increased, there were proportionately greater decreases in ethanol intake when saccharin was concurrently available compared to when water was available. There was a 35–50% reduction in ethanol deliveries due to concurrent saccharin (versus water) at FR 4, compared to a 55–75% reduction at FR 128. Cost of ethanol (FR), income level and the availability of a nondrug reinforcer are all variables that modify ethanol-reinforced behavior, and income alters the relative preference for a drug versus nondrug reinforcer.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 126 (1996), S. 281-285 
    ISSN: 1432-2072
    Keywords: Caffeine ; Cocaine base ; Crack ; Drug self-administration ; Fixed ratio ; Reinforcing effects ; Rhesus monkeys ; Smoking
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several recent studies have shown that caffeine potentiates the reinforcing, discriminative stimulus, and motor activating effects of cocaine in rats. The present study was designed to determine whether oral caffeine pretreatment would enhance the reinforcing effects of cocaine in rhesus monkeys trained to self-administer smoked cocaine base. The effects of oral caffeine pretreatment (0, 100, or 200 mg) and fixed-ratio (FR) value on cocaine-base smoking were evaluated in four male rhesus monkeys. Monkeys responded on a lever under a fixed-ratio (FR) schedule (FR 128, 256, 512, 1024, 2048, or 4096) and then made five inhalations on a smoking spout to gain access to volatilized cocaine base (0.25 or 1.0 mg/kg per delivery) during daily experimental sessions. Twenty pellets [20 non-caffeinated (0 mg caffeine), ten non-caffeinated+ten caffeinated (100 mg caffeine), or 20 caffeinated (200 mg caffeine) pellets] were administered 30 min prior to experimental sessions. The lever FR value was held constant within each experimental session, but was increased after 3 consecutive days of stable responding. Although the number of smoke deliveries that was self-administered significantly decreased from FR 128 to FR 4096, it did not change as a function of cocaine dose across the range of FR values tested. However, the interaction between cocaine dose and caffeine pretreatment was statistically significant. Compared to 0 mg caffeine, three of four monkeys pretreated with 200 mg caffeine responded for a greater number of smoke deliveries when they were maintained on a cocaine dose of 1.0 mg/kg per delivery, but not 0.25 mg/kg per delivery. Thus, caffeine pretreatment can produce small, but statistically significant increases in smoked cocaine self-administration in rhesus monkeys.
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