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  • 1
    Electronic Resource
    Electronic Resource
    Discriminative stimulus properties of d-amphetamine-pentobarbital combinations (1980)
    Springer
    Psychopharmacology 68 (1980), S. 269-276 
    Details
    ISSN: 1432-2072
    Keywords: d-Amphetamine ; Pentobarbital ; Drug interactions ; Discriminative stimulus properties of drugs ; Discrimination history ; Key peck ; Pigeons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pigeons were trained to discriminate IM injections of 1.0 mg/kg d-amphetamine from water, 5.6 mg/kg pentobarbital from water, or 1.0 mg/kg d-amphetamine from 5.6 mg/kg pentobarbital by requiring them to peck different response keys depending on which substance was administered prior to the session. Excellent stimulus control was achieved under all conditions with close to 100% of the responses occurring on the injection-correlated key. In tests with doses different from those used in training, the percentage of responses on the drug key was directly related to drug dose. When d-amphetamine was given to birds trained to discriminate pentobarbital from water or when pentobarbital was given to birds trained to discriminate d-amphetamine from water, responding occurred predominately on the water-correlated key. d-Amphetamine produced a dose-related antagonism of the effects of pentobarbital for birds trained to discriminate pentobarbital from water or from d-amphetamine. Rates of responding on the drug key were generally highes after administration of the drug doses used in discrimination training; but response rates were not systematically related to the percentage of responses occurring on the drug key. All birds were subsequently trained to discriminate a combination of 1.0 mg/kg d-amphetamine and 5.6 mg/kg pentobarbital from either 1.0 mg/kg d-amphetamine or 5.6 mg/kg pentobarbital alone, demonstrating that the discriminative stimulus properties of amphetamine-pentobarbital combinations are different from either drug alone. Several of the drug effects reported were related to the drug discrimination that had been established.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00428114
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  • 2
    Electronic Resource
    Electronic Resource
    Evaluation of the effects of opioid agonists and antagonists under a delayed matching-to-sample procedure in pigeons (1987)
    Springer
    Psychopharmacology 93 (1987), S. 230-236 
    Details
    ISSN: 1432-2072
    Keywords: Pigeons ; Delayed matching-to-sample ; Conditional discriminations ; Morphine ; l-Methadone ; U 50,488 ; Ethylketocyclazocine ; Phencyclidine ; (+) N-Allylnormetazocine ; Naloxone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of several opioid agonists and antagonists were examined in pigeons performing under a delayed matching-to-sample procedure. The mu agonists morphine and l-methadone, the kappa agonists U 50,488 and ethylketocyclazocine, and the opioid antagonist naloxone had no effect on the accuracy of responding. These drugs were, however, behaviorally active as evidenced by the dose-dependent decreases in rates of responding associated with their administration. In contrast, the sigma agonists (+) N-allylnormetazocine and phencyclidine decreased the accuracy of responding in a dose-dependent fashion. The relative magnitude of these drug-induced decreases in accuracy were similar across the no delay (0-s), short (2-s), and long (8-s) delay intervals. For these drugs, accuracy-decreasing effects were obtained only at doses that reduced rates of responding. The results of the present investigation parallel those reported in pigeons responding under drug discrimination tasks, in which the discriminative stimulus properties produced by the mu and kappa agonists are similar to each other but distinguishable from those produced by the sigma agonists.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00179940
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  • 3
    Electronic Resource
    Electronic Resource
    Differential effects of opioid and nonopioid analgesics on conditional discriminations in pigeons (1988)
    Springer
    Psychopharmacology 94 (1988), S. 405-411 
    Details
    ISSN: 1432-2072
    Keywords: Conditional discriminations ; Opioid analgesics ; Stimulus control ; Fixed-consecutive-number ; Pigeons ; Nonopioid analgesics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Under the fixed-consecutive-number schedule (FCN), pigeons were reinforced for responding eight or more times on one response key (work key), and then responding once on a second response key. In one component of this schedule, an external stimulus signalled the completion of the response requirement on the work key (FCN 8-SD), whereas no stimulus change was programmed under the other (FCN 8). Across a range of doses, the mu opioid agonist morphine, the kappa opioid agonist U50,488 and the opioid antagonist naloxone had no consistent effect on accuracy under either FCN schedule. Naloxone and U50,488 produced a general flattening of the conditional probability functions by decreasing the conditional probability of response runs exceeding the minimum response requirement of eight consecutive responses on the work key. The sigma agonists phencyclidine and (+)N-allylnormetazocine and the nonopioid analgesics clonidine and l-nantradol produced large decreases in accuracy under the FCN 8 and small decreases under the FCN 8-SD. With the exception of (+)N-allylnormetazocine, these drugs consistently increased the conditional probability of responses runs shorter than the minimum response requirement on the work key. These findings indicate that the accuracy-altering effects of some opioid and nonopioid analgesics depend in part on the type of discrimination task.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00174698
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  • 4
    Electronic Resource
    Electronic Resource
    Joint effects of ethanol and caffeine on schedule-controlled responding in the pigeon (1979)
    Springer
    Psychopharmacology 62 (1979), S. 141-144 
    Details
    ISSN: 1432-2072
    Keywords: Ethanol ; Caffeine ; Schedule-controlled behavior ; Pigeons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Interactions between ethanol and caffeine were studied in pigeons keypecking under a multiple fixed ratio 30 fixed interval 5-min schedule of food presentation. When ethanol was administered alone, rates of responding under both components of the multiple schedule were generally decreased in a dose-related manner. Caffeine alone either decreased or had no effect on rates of responding under both the fixed ratio and fixed interval components. When caffeine and ethanol were combined, doses of caffeine which did not decrease rates of responding when given alone attenuated the rate-decreasing effects of ethanol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427127
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  • 5
    Electronic Resource
    Electronic Resource
    Antinociceptive effects of the kappa opioid, U50,488: lack of modulation by 5-HT2 antagonists (1993)
    Springer
    Psychopharmacology 112 (1993), S. 116-120 
    Details
    ISSN: 1432-2072
    Keywords: Kappa opioids ; U50,488 ; Serotonin ; 5-HT2 antagonists ; Ketanserin ; Pirenperone ; LY 53857 ; Shock titration ; Antinociception ; Analgesia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The kappa opioid, U50,488, was examined alone and in combination with the 5HT2 antagonists, ketanserin, pirenperone and LY 53857. Squirrel monkeys responded under a shock titration procedure in which shock intensity increased every 15 s from 0.01 to 2.0 mA in 30 steps. Five responses terminated the shock for 15 s, after which the shock resumed at the next lower intensity. The level at which the monkeys kept the shock 50% of the time (median shock level/MSL) was determined. U50,488 alone produced dose-dependent increases in median shock level whereas none of the 5-HT2 antagonists altered responding under this procedure. When ketanserin (0.032–5.6 mg/kg) was administered in combination with U50,488, very high doses of ketanserin (3.2–5.6 mg/kg) shifted the U50,488 dose-effect curve to the left. Neither pirenperone (0.032–10.0 µg/kg) nor LY53857 (0.01–0.32 mg/kg) altered the U50,488 dose-effect curve in any monkey. Taken together, these data do not support a role for the 5-HT2 system in kappa-induced antinociception in the primate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02247371
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  • 6
    Electronic Resource
    Electronic Resource
    The competitive NMDA receptor antagonist LY235959 modulates the progression of morphine tolerance in rats (1999)
    Springer
    Psychopharmacology 142 (1999), S. 209-214 
    Details
    ISSN: 1432-2072
    Keywords: Key words NMDA antagonists ; Opioid ; Antinociception ; Tail-withdrawal ; Tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A rat warm-water tail-withdrawal procedure was used to examine the effects of chronic administration of the competitive NMDA receptor antagonist LY235959 in morphine tolerant rats. Morphine dose-dependently increased tail-withdrawal latencies from 55°C water. When morphine (10 mg/kg) was administered twice-daily for 7 days, the morphine dose-effect curves shifted 0.3–0.5 log unit to the right. When morphine was administered for an additional 7 days, the morphine dose-effect curve shifted 0.4 log unit further to the right. Co-administration of LY235959 (1, 3, 10 mg/kg) along with morphine prevented the development of tolerance observed during the second week of chronic morphine administration. Although the highest dose of LY235959 (10 mg/kg) partially reversed tolerance in five of seven rats, tolerance was not reversed by lower doses of LY235959. These data suggest that NMDA receptor antagonists may effectively prevent the progressive development of morphine tolerance at doses that are not sufficient to reverse pre-established morphine tolerance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050881
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  • 7
    Electronic Resource
    Electronic Resource
    Serotonin involvement in the discriminative stimulus effects of κ opioids in pigeons (1993)
    Springer
    Psychopharmacology 111 (1993), S. 69-77 
    Details
    ISSN: 1432-2072
    Keywords: κ opioids ; Drug discrimination ; Serotonin ; p-CPA ; Pigeons ; 8-OH-DPAT ; NAN-190 ; Buspirone ; Ketanserin ; Spiradoline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of the present study was to examine the role of serotonin (5HT) in the discriminative stimulus effects ofκ opioids. Pigeons were trained to discriminate 5.6 mg/kg of theκ opioid, U50,488, from water. During substitution tests, both U50,488 and anotherκ opioid, spiradoline, produced 〉80% responding on the U50,488-appropriate key. In contrast, the nonopioid compound, phencyclidine and several serotonergic compounds failed to substitute for the U50,488 discriminative stimulus across a wide range of doses. During combination tests, the selective 5HT1A agonist, 8-OH-DPAT (0.001–3.2 mg/kg), dose-dependently attenuated the discriminative stimulus effects of 5.6 mg/kg U50,488 and 3.2 mg/kg spiradoline. This effect was reversed by the 5HT1A antagonist, NAN-190 (0.01–1 mg/kg), in a dose-dependent manner. Buspirone (0.01–10 mg/kg), a 5HT1A partial agonist, also attenuated the discriminative stimulus effects of the training dose of U50,488 but ipsapirone, another 5HT1A partial agonist, did not. Ketanserin, a 5HT2 antagonist, and MDL72222, a 5HT3 antagonist, attenuated the effects of U50,488, whereas the 5HT1B,1C agonist, mCPP, and the 5HT2 agonist, DOI, did not. Depletion of 5HT withp-CPA also attenuated U50,488's discriminative stimulus effects. Taken together, the results suggest that serotonin release is an important component in the discriminative stimulus effects produced byκ opioids; however, the effects of DOI and mCPP alone suggest that activation of post-synaptic 5HT receptors is not sufficient to produce the full spectrum ofκ opioid discriminative stimulus effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02257409
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  • 8
    Electronic Resource
    Electronic Resource
    The role of serotonergic receptors in the effects ofmu opioids in squirrel monkeys responding under a titration procedure (1996)
    Springer
    Psychopharmacology 126 (1996), S. 42-49 
    Details
    ISSN: 1432-2072
    Keywords: Morphine ; Serotonin ; Antinociception ; Shock titration ; Squirrel monkeys
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This experiment was conducted to determine whether drugs acting on brain serotonin modulate the effects of themu opioid, morphine, as measured by the squirrel monkey shock titration procedure and, if so, whether serotonergic modulation is mediated via specific 5HT receptor subtypes. Under this procedure, electric shock was delivered to the monkey's tail and scheduled to increase once every 15 s from 0.01 to 2.0 mA in 30 steps. Five responses on a lever during the 15-s shock period terminated the shock for 15 s, after which the shock resumed at the next lower intensity. The intensity below which monkeys maintained shock 50% of the time (median shock level or MSL) and rate of responding (RR) in the presence of shock were determined under control conditions and after administration of morphine alone and in combination with various serotonergic compounds. Morphine increased median shock level and decreased rate of responding in a dose-dependent manner. These effects of morphine were attenuated by the 5HT1A receptor agonists, 8-OH-DPAT [(+)-8-hydroxy-2(di-n-propylamino tetralin HBr] and ipsapirone. The effects of morphine were not altered by the 5HT1A receptor antagonist, NAN-190 [1-(2-methoxyphenyl)-4-[4-(2-phthalimido) butyl] piperazine HBr], the 5HT2 receptor antagonist, ketanserin, the 5HT3 receptor antagonist, MDL 72222 [3-tropanyl-3,5-dichlorobenzoate], the alpha2 adrenergic antagonist, yohimbine, or the alpha2 adrenergic agonist, clonidine. These results suggest that 5HT1A receptors may be involved in the effects of morphine in the shock titration procedure, whereas 5HT2, 5HT3 and alpha2 adrenergic receptors do not appear to play a role in morphine's effects in this procedure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246409
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  • 9
    Electronic Resource
    Electronic Resource
    Role of morphine maintenance dose in the development of tolerance and its attenuation by an NMDA receptor antagonist (2000)
    Springer
    Psychopharmacology 148 (2000), S. 59-65 
    Details
    ISSN: 1432-2072
    Keywords: Key words NMDA receptor ; Opioid ; Antinociception ; Tail-withdrawal ; Tolerance ; Maintenance dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Current research shows that N-methyl-d-aspartate (NMDA) receptor antagonists attenuate the development of morphine tolerance in rodent antinociceptive assays. Objective: The purpose of this study was to determine the role of morphine maintenance dose in the attenuation of morphine tolerance by the competitive NMDA receptor antagonist, LY235959. Methods: A rat warm-water tail-withdrawal procedure was used to measure the antinociceptive effects of morphine and LY235959. In this procedure, the distal 8 cm of each rat’s tail is immersed in 40° (non-noxious) and 55°C (noxious) water, and the latency to remove the tail is recorded. Results: Morphine (0.3–10 mg/kg, SC) produced dose-dependent increases in tail-withdrawal latencies from the 55°C water. Following determination of the morphine dose-effect curves, rats were administered chronically one of three doses of morphine (10, 20, or 40 mg/kg) either alone or in combination with LY235959 (1.0, 3.0, or 5.6 mg/kg, SC) twice daily for 7 days. Chronic administration of 10, 20, and 40 mg/kg morphine produced rightward shifts in the morphine dose-effect curves of approximately 3-, 6-, and 12-fold, respectively. When LY235959 (1.0–5.6 mg/kg) was co-administered with 10 mg/kg morphine, the development of morphine tolerance was attenuated in a dose-dependent manner, with complete prevention observed following 3.0 mg/kg LY235959. LY235959 (1.0, 3.0 mg/kg) also attenuated the development of tolerance to 20 and 40 mg/kg morphine; however, tolerance was not completely prevented. Administering 3.0 mg/kg LY235959 along with 20 and 40 mg/kg morphine was functionally equivalent to treating rats with half the amount of morphine. Conclusion: These data suggest that the maintenance dose of morphine, and thus the magnitude of tolerance, can determine the effectiveness of an NMDA receptor antagonist to attenuate morphine tolerance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050025
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