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  • 1
    ISSN: 1432-2072
    Keywords: Key words Baclofen ; Cocaine ; Extinction ; Intravenous self-administration ; Maintenance dose ; Rat ; Reinstatement of responding ; Relapse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: Recent studies suggest that the GABAB receptor agonist, baclofen, may be a useful pharmacotherapy for cocaine abuse. Objectives: To investigate further the effects of baclofen on maintenance and reinstatement of cocaine-reinforced behavior in rats. Methods: Two groups of rats were trained to self-administer IV cocaine (0.2 or 0.4 mg/kg per infusion) during daily 7-h sessions under a fixed-ratio 1 schedule. Rats were pretreated with baclofen (1.25, 2.5 or 5 mg/kg IP) or saline before the session for 5 consecutive days. An additional group of rats was trained to self-administer IV cocaine (0.4 mg/kg per infusion) during the first 2 h of daily 7-h sessions. Cocaine was replaced by saline for the remaining 5 h of the session. Once behavior had stabilized over the 7-h period, priming injections of saline (IV), cocaine (3.2 mg/kg IV) or baclofen (1.25 or 2.5 mg/kg IP) were administered prior to hour 4. Injections of baclofen (1.25 or 2.5 mg/kg IP) or saline were also given before priming injections of cocaine. Results: Pretreatment with the two higher doses of baclofen (2.5 and 5 mg/kg) decreased the number of cocaine infusions in both maintenance groups (0.2 and 0.4 mg/kg) over the 5-day treatment period. Baclofen had a greater suppressant effect on responding maintained by the lower dose of cocaine. Priming injections of baclofen (1.25 and 2.5 mg/kg) or saline did not reinstate responding. However, these same doses of baclofen dose-dependently reduced the reinstatement of responding produced by priming injections of cocaine. Conclusions: 1) The magnitude of the suppressant effects of baclofen on maintenance of cocaine self-administration depends upon the maintenance dose, 2) baclofen may be useful in preventing reinstatement of cocaine-seeking behavior, and 3) compared to maintenance, reinstatement of responding is more sensitive to the suppressant effects of baclofen.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Key words Behavioral economics ; Cocaine base ; Crack ; Demand ; Dopamine antagonist ; Drug self-administration ; Elasticity ; Raclopride ; Rhesus monkey ; SCH 23390 ; Unit price
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Previous studies suggest that dopamine antagonists may reduce the reinforcing effects of cocaine. However, the effects of these antagonists on the demand for smoked cocaine base have not been quantified. Objectives: To evaluate the effects of selective D1 (SCH 23390) and D2 (raclopride) dopamine receptor antagonists on the demand for smoked cocaine base in rhesus monkeys using a behavioral economic analysis. Methods: Six rhesus monkeys were trained to self-administer smoked cocaine base (1.0 mg/kg/delivery) under chained fixed-ratio (FR) schedules (FR64, 128, 256, 512, 1024 or 2048 for lever presses and FR5 for inhalations) during daily 4-h sessions. A maximum of ten smoke deliveries were available. After 5 days of stable behavior at each FR, SCH 23390 (0.01 and 0.056 mg/kg) or raclopride (0.03 and 0.056 mg/kg) were injected intramuscularly, before each session, for 3 consecutive days. Results: Pretreatment with both antagonists dose-dependently reduced cocaine intake across most FR values tested; however, the decrease in consumption was greater at the higher unit prices than at the lower unit prices. A statistical estimate of the price (FR) at which maximum responding occurred (Pmax) was decreased during drug pretreatment, indicating weakened reinforcing effectiveness of cocaine. Conclusions: These data suggest that both antagonists reduce the reinforcing effectiveness of smoked cocaine base, and they have a greater effect on cocaine consumption at higher FR values.
    Type of Medium: Electronic Resource
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  • 3
    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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  • 4
    ISSN: 1432-2072
    Keywords: Key words Acquisition ; Alternative reinforcer ; Dose ; Drug self-administration ; Oral phencyclidine ; PCP ; Rhesus monkeys ; Saccharin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The effects of drug dose and a non-drug alternative reinforcer on acquisition of oral PCP self-administration in rhesus monkeys were examined. Acquisition was studied using three groups of monkeys (seven subjects per group). One group received a low PCP dose (0.0375 mg/delivery) and the other two received a high PCP dose (0.15 mg/delivery). One of the high dose groups had concurrent access to a saccharin solution (0.03% w/v) and water during the intersession (17.5-h) period. Food non-restricted monkeys were initially given access to water under a fixed-ratio (FR) 1 schedule during daily 3-h sessions. Water was then replaced with PCP during the session. The monkeys were then reduced to 85% of their free-feeding body weights and fed before the session, and the FR value was increased from 1 to 2, 4 and 8. Subsequently, food was given post-session and water and PCP were available under concurrent FR 8 schedules. At this final step of the procedure, acquisition of PCP self-administration was considered to occur if PCP intake consistently exceeded water intake. When all three groups were given concurrent access to PCP and water, PCP intake was greater than water intake only in the group of monkeys receiving the high PCP dose. PCP intake increased when water replaced saccharin during intersession in the high PCP dose group. Within-group data revealed that 85.7% of monkeys acquired PCP reinforcement in the group given access to the high PCP dose while only 42.8% acquired in the other two groups. These data suggest that drug dose and presence of alternative non-drug reinforcers affect acquisition of drug self administration in non-human primates.
    Type of Medium: Electronic Resource
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  • 5
    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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