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  • 1
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 215 (1973), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 91 (1987), S. 213-216 
    ISSN: 1432-2072
    Keywords: Pigeon ; Morphine ; Naltrexone ; β-Funaltrexamine ; Opioid antagonism ; Drug discrimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Antagonistic actions of the irreversible, μ-selective antagonist β-funaltrexamine (β-FNA) were evaluated in pigeons trained to discriminate among intramuscular injections of morphine (5.6 mg/kg), saline, and naltrexone (10.0 mg/kg). β-FNA administered alone (1.0 or 10.0 mg/kg) failed to mimic the discriminative stimulus effects of morphine or naltrexone. β-FNA attenuated the discriminative stimulus effects of morphine. A three-fold larger dose of morphine was required for complete generalization when pigeons were pretreated with a dose of 1.0 mg/kg β-FNA. A dose of 10.0 mg/kg β-FNA completely antagonized the morphine discriminative stimulus, so that pigeons responded predominantly on the saline key up to doses of morphine that suppressed responding. Doses of β-FNA that attenuated the effects of morphine had no effect on the discriminative stimulus effects of naltrexone. These results demonstrate that, like naltrexone, β-FNA attenuates the discriminative stimulus effects of morphine in pigeons and, at sufficiently large doses, antagonizes morphine in an unsurmountable manner. β-FNA does not, however, share discriminative stimulus properties with naltrexone in these pigeons, and fails to attenuate the discriminative stimulus effects of naltrexone, lending support to the suggestion that naltrexone exerts discriminative stimulus effects under these experimental conditions predominantly by a non-mu opioid mechanism.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: Drug discrimination ; NMDA antagonists Phencyclidine ; CGS 19755 ; Pigeons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of the present studies was to examine representative uncompetitive and competitive NMDA antagonists, as well as the glycine/NMDA antagonist, HA 966, in pigeons trained to discriminate either PCP or CGS 19755 from saline. Separate groups of pigeons were trained to discriminate either the uncompetitive, phencyclidine (PCP; 0.32 and 1.0 mg/kg, IM), or the competitive, CGS 19755 (cis-4-phosphonomethyl-2-piperidine-carboxylic acid; 1.8 mg/kg, IM), NMDA antagonists from saline. Uncompetitive and competitive NMDA antagonists were examined in generalization studies, as were the racemate and the (+) and (−) stereoisomers of HA 966 (3-amino-1-hydroxypyrrolid-2-one). Dizocilpine (MK 801) was fully generalized to PCP but not to CGS 19755. All competitive NMDA antagonists tested were fully generalized to CGS 19755, but not to PCP. The competitive antagonists, however, produced 〉50% PCP-appropriate responding. The (+) isomer of HA 966 was fully generalized by three of four pigeons discriminating PCP (1.0 mg/kg) or CGS 19755, whereas the racemate and the (−) isomer produced 〈40% drugappropriate responding in either group. Neither NMDA, morphine, nor pentobarbital produced 〉10% drug-appropriate responding in either discrimination group. The competitive antagonists tended to produce peak drug-appropriate responding at times greater than 60 min after administration, whereas uncompetitive antagonists produced peak drug-appropriate responding at earlier times. HA 966 also had a relatively slow onset of action as compared to PCP. These results suggest that antagonists acting at different modulatory sites of the NMDA receptor complex produce similar, but not identical, discriminative stimuli.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 118 (1995), S. 107-115 
    ISSN: 1432-2072
    Keywords: Benzodiazepines ; Drug abuse ; Physiological dependence ; Behavioral effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This article deals with some of the recent evidence bearing on the issues of the liability of benzodiazepines to lead to abuse, dependence, and adverse behavioral effects. Reviews of epidemiological, clinical and experimental literature indicated that the previous conclusion about abuse of these drugs still holds: the vast majority of the use of benzodiazepines is appropriate. Problems of nonmedical use arise nearly exclusively among people who abuse other drugs. Nevertheless, there are reasons for concern about patients who take benzodiazepines regularly for long periods of time. These drugs can produce physiological dependence when taken chronicaly, and although this does not appear to result in dose escalation or other evidence of “psychological dependence,” physiological dependence can result in patient discomfort if drug use is abruptly discontiniued. Also, physicians are currently prescribing shorter-acting benzodiazepines in preference to longer-acting benzodiazepines. The shorter-acting drugs can produce a more intense withdrawal syndrome following chronic administration. Furthermore, rates of use of benzodiazepines increase with age, and elderly patients are more likely than younger ones to take the drug chronically. The clearest adverse effect of benzodiazepines is impairment of memory. This, too, may be particular concern in older patients whose recall in the absence of drug is typically impaired relative to younger individuals, and who are more compromised following drug administration.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2072
    Keywords: Key words Opioid antagonists ; Oral self-administration ; Intravenous self-administration ; Alcohol ; Operant behavior
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  These experiments evaluated the ability of naltrexone (NTX) to reduce selectively oral and IV ethanol-reinforced responding, and examined the ethanol-NTX interaction in terms of the competitive opioid antagonist property of NTX. Five rhesus monkeys self-administered ethanol or sucrose and concurrently available water. Ethanol concentration was varied from 0.25% to 8% (w/v). Naltrexone (0.032–0.32 mg/kg) or saline was given IM 30 min prior to some drinking sessions. NTX (0.32 mg/kg) reduced ethanol-reinforced responding at the concentration that maintained the most responding (1% or 2%). NTX (0.1 mg/kg) reduced ethanol-reinforced responding, both at a low ethanol concentration (0.25%) that produced little ethanol intake (g/kg), and at a higher concentration (4%) with an appreciable intake. Thus, NTX (0.1 mg/kg) shifted the ethanol concentration-consumption curve down, in an insurmountable manner. NTX (0.1 and 0.32 mg/kg) also reduced reinforced responding for sucrose 100 g/l. In another experiment, three rhesus monkeys were given opportunities to self-administer ethanol IV. NTX (0.1 mg/kg) reduced the number of ethanol injections obtained by the monkeys at all ethanol doses tested (0.01, 0.032, and 0.1 g/kg per injection).The dose-effect curve was also shifted down. These results showed that NTX reduced behavior maintained by either ethanol or sucrose non-selectively. Furthermore, the ability of NTX to suppress ethanol-reinforced responding did not depend on the route of ethanol administration and was not overcome by increasing the concentration or dose per injection of ethanol.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2072
    Keywords: Key words Capsaicin ; Antinociception ; Peripheral cannabinoid receptor ; Inflammatory pain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: Cannabinoids can reduce nociceptive responses by acting on peripheral cannabinoid receptors in rodents. Objectives: The study was conducted to evaluate the hypothesis that local administration of Δ9-tetrahydrocannabinol (Δ9-THC) can attenuate capsaicin-induced nociception in rhesus monkeys. Methods: Capsaicin (100 µg) was applied locally in the tail of rhesus monkeys to evoke a nociceptive response, thermal allodynia, in normally innocuous 46°C water. Δ9-THC (10–320 µg) was coadministered with capsaicin in the tail to assess local antinociceptive effects. In addition, a local antagonism study was performed to confirm the selectivity of Δ9-THC action. Results:Δ9-THC dose-dependently inhibited capsaicin-induced allodynia. This local antinociception was antagonized by small doses (10–100 µg) of the cannabinoid CB1 antagonist, SR141716A, applied in the tail. However, 100 µg SR141716A injected subcutaneously in the back did not antagonize local Δ9-THC. Conclusions: These results indicate that the site of action of locally applied Δ9-THC is in the tail. It provides functional evidence that activation of peripheral cannabinoid CB1 receptors can attenuate capsaicin-induced thermal nociception in non-human primates and suggests a new approach for cannabinoids in pain management.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-2072
    Keywords: Key words Opioid antagonists ; Alcohol reinforcement ; Self-administration ; Primates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: The endogenous opioid system may mediate the reinforcing effects of ethanol as well as sweet-tasting solutions. For example, opioid antagonists, such as naltrexone, reduce ethanol- and sucrose-reinforced responding in rhesus monkeys. If these effects are due to blockade of the µ-receptor, then an opioid antagonist such as quadazocine with a receptor selectivity profile similar to that of naltrexone should reduce responding at doses correlated with its µ-selectivity. Objectives: To determine whether quadazocine would reduce responding for ethanol and sucrose at µ-selective doses, and whether quadazocine and naltrexone would reduce responding for a bitter-tasting drug solution such as phencyclidine. Methods: Rhesus monkeys were given access to ethanol, sucrose, or phencyclidine concurrently with water. Prior to the drinking sessions, quadazocine (0.032–3.2 mg/kg) or saline was injected intramuscularly. During the phencyclidine experiment, naltrexone (0.1 and 0.32 mg/kg) was also tested. Results: The highest quadazocine doses (1 and 3.2 mg/kg) reduced ethanol and sucrose fluid deliveries without affecting the concurrently available water. Quadazocine reduced the fluid deliveries of both phencyclidine and water when concurrently available. Naltrexone reduced only phencyclidine fluid deliveries. Conclusions: The opioid antagonist effect on oral-reinforced responding is not selective for ethanol or sweet-tasting solutions; responding for phencyclidine was reduced as well. Quadazocine and NTX may reduce responding by blocking the µ-receptor because the relative potency of these antagonists to reduce oral self-administration was similar to their relative potency to produce withdrawal in morphine-dependent monkeys. However, water responding was low in these experiments, and thus we cannot rule out rate-dependent effects of the antagonists.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-2072
    Keywords: Key words Neuroactive steroid ; Barbiturate ; Self-administration ; Discriminative stimulus effects ; Rhesus monkey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale and Objectives: The present study was designed to assess possible abuse-related effects of the endogenous neuroactive steroid pregnanolone (3α-hydroxy-5β-pregnan-20-one) and the orally bioavailable, water-soluble neuroactive steroid pro-drug Co 8-7071 (3α,21-dihydroxy-3β-trifluoromethyl-5β-pregnan-20-one, 21-hemisuccinate). Methods: Four rhesus monkeys were prepared with chronic intravenous (IV) catheters and trained to press a lever under a ten-response fixed-ratio (FR) schedule of methohexital injection (0.1 mg/kg per injection). Three rhesus monkeys were trained to discriminate intragastric infusions of pentobarbital (10 mg/kg) from saline infusions under a FR5 schedule of stimulus-shock termination. Results: At least two doses of pregnanolone (0.003–0.1 mg/kg per injection) maintained injections per session above saline levels in the four monkeys tested, whereas Co 8-7071 (0.01–1.0 mg/kg per injection) maintained injections per session above saline levels in two of four monkeys at relatively low levels of injections per session. In rhesus monkeys trained to discriminate pentobarbital, IV pregnanolone injections (0.1–1.7 mg/kg, 5-min presession) dose-dependently reproduced the discriminative stimulus effects of pentobarbital in all monkeys tested. Intravenous administration of Co 8-7071 (1–10 mg/kg, 5-min presession) resulted in a dose-dependent increase to 〉80% pentobarbital-appropriate responding in two of three monkeys tested. Following intragastric infusions of Co 8-7071 (1.0–30 mg/kg), ≥80% pentobarbital-appropriate responding occurred in one out of three monkeys at 10 mg/kg when administered 60 min before the session. When administered 120 min before the session, however, 10–30 mg/kg Co 8-7071 reproduced the discriminative stimulus effects of pentobarbital in each of the three monkeys tested. Conclusions: These data demonstrate barbiturate-like abuse-related effects that differed between two pregnane steroids. Whereas pregnanolone functioned as a reinforcer, suggesting that this compound has abuse potential, Co 8-7071 did not, despite having pentobarbital-like discriminative effects.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 43 (1975), S. 13-17 
    ISSN: 1432-2072
    Keywords: Drug Self-Administration ; DITA ; d-Amphetamine ; Food Reinforcement ; Fixed-Ratio ; Lever-Press ; Rhesus Monkeys
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intravenous pretreatment with DITA (0.1–1.0 mg/kg) decreased the rate of food-reinforced lever pressing in rhesus monkeys. Response rate decreases were dose-dependent but showed the development of tolerance. Self-administration of DITA was initiated and maintained in each of three monkeys when 30 lever presses were required to produce each injection. Maximal response rate during periods of drug availability was maintained by 0.03 mg/kg/injection while higher and lower doses (0.01 and 0.10 mg/kg/injection) maintained lower response rates. Response rate in periods of food availability immediately preceding drug periods was relatively constant across sessions; response rate in periods of food availability immediately following drug periods, however, decreased with increasing amounts of drug self-administered. Replication of initial self-administration doses produced results comparable to original determinations in contrast to the tolerance observed with DITA effects upon food-reinforced responding. DITA was about 3 times less potent than d-amphetamine in maintaining response rates in drug periods and in decreasing the rate of subsequent food-reinforced responding.
    Type of Medium: Electronic Resource
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