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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The specific opioid receptor antagonist naloxone attenuates the behavioral and neurochemical effects of amphetamine. Furthermore, the amphetamine-induced increase in locomotor activity is attenuated by intracisternally administered naltrindole, a selective δ-opioid receptor antagonist, but not by the irreversible μ-opioid receptor antagonist β-funaltrexamine. Therefore, this research was designed to determine if naltrindole would attenuate the neurochemical response to amphetamine as it did the behavioral response. In vivo microdialysis was used to monitor the change in extracellular concentrations of dopamine in awake rats. Naltrindole (3.0, 10, or 30 µg) or vehicle was given 15 min before and β-funaltrexamine (10 µg) or vehicle 24 h before the start of cumulative dosing, intracisternally in a 10-µl volume, while the rats were lightly anesthetized with methoxyflurane. Cumulative doses of subcutaneous d-amphetamine (0.0, 0.1, 0.4, 1.6, and 6.4 mg/kg) followed pretreatment injections at 30-min intervals. Dialysate samples were collected every 10 min from either the striatum or nucleus accumbens and analyzed for dopamine content by HPLC. Amphetamine dose-dependently increased dopamine content in both the striatum and nucleus accumbens, as reported previously. Naltrindole (3.0, 10, and 30 µg) significantly reduced the dopamine response to amphetamine in the striatum. In contrast, 30 µg of naltrindole did not modify the dopamine response to amphetamine in the nucleus accumbens. On the other hand, β-funaltrexamine (10 µg) had no effect in the striatum but significantly attenuated the amphetamine-induced increase in extracellular dopamine content in the nucleus accumbens. These data suggest that δ-opioid receptors play a relatively larger role than μ-opioid receptors in mediating the amphetamine-induced increase in extracellular dopamine content in the striatum, whereas μ-opioid receptors play a larger role in mediating these effects in the nucleus accumbens.
    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 398 (1982), 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 77 (1982), S. 295-300 
    ISSN: 1432-2072
    Keywords: Phencyclidine ; Opioids ; Naltrexone ; Drug discrimination ; Narcotic antagonists ; Squirrel monkeys
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The opioids SKF 10047, dl-cyclazocine, and dextrorphan have been shown to have phencyclidine (PCP)-like discriminative stimulus properties in the rat. In order to extend the generality of this observation, the stimulus effects of these and other opioids were evaluated in squirrel monkeys trained to discriminate between IM injections of saline and 0.25 mg/kg of PCP in a two-choice discrete-trial avoidance paradigm. Stimulus control of behavior was characterized by the reliable completion of at least 22 trials of a 25-trial session on the appropriate choice lever after an injection of saline or PCP. In tests of stimulus generalization, SKF 10047, d-cyclazocine, dextrorphan, normetazocine, dl-cyclazocine, l-cyclazocine, and dextromethorphan occasioned dose-related increases in PCP-appropriate responding. The first four of these compounds and, under some conditions, l- and dl-cyclazocine, produced stimulus control of behavior comparable to that produced by the PCP training dose. Six other opioids occasioned responding only on the saline-appropriate lever: ethylketocyclazocine, ketocyclazocine, levorphanol, levallorphan, pentazocine, naltrexone. Naltrexone (1.0 or 4.0 mg/kg) attenuated slightly the PCP-like stimulus effects of SKF 10047 and dextrorphan, but increased PCP-appropriate responding with l- and dl-cyclazocine and levorphanol by enabling higher doses of these drugs to be tested without disruption of responding. The PCP-like stimulus effects of certain opioids appear to be mediated at neuronal substrates acted upon by PCP rather than at sites typically associated with opiate activity. These neuronal sites of action common to opioids and PCP may correspond to the sigma “opiate” receptor.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 70 (1980), S. 11-18 
    ISSN: 1432-2072
    Keywords: Morphine ; Naloxone ; Physical dependence ; Operant behavior ; Withdrawal ; Tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chronic morphine treatment has been reported to induce long-lasting changes in the responses of animals to the subsequent administration of morphine or narcotic antagonists. However, there have been few systematic studies in which the effects of morphine or narcotic antagonists have been compared in the same group of animals before, during, and after chronic morphine administration. Rats were trained to press a lever on a variable interval (1 min) schedule of food presentation and dose-response curves were determined for morphine (0.3–30 mg/kg) and naloxone (0.003–10 mg/kg) in the same group of animals prior to, during, and following morphine dependence. Dependence was induced and maintained by scheduled access to 0.05% morphine drinking solution for 10 min every 6 h. Response rates and fluid intake remained constant over the 9 month study. The dose-response curves for morphine and naloxone in predependent and dependent animals were similar to those previously reported in studies using other schedules of reinforcement and different techniques for establishing morphine dependence: chronic morphine treatment produced a threefold decrease in the effect of morphine and a dramatic increase in the effectiveness of naloxone in decreasing response rate. The altered sensitivity of dependent rats to morphine and naloxone was completely reversed in the post-dependent animals, within 4 weeks after the withdrawal of morphine. Scheduled access to a morphine solution affords a simple means of maintaining morphine-tolerant and dependent animals for long-term behavioral studies.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 80 (1983), S. 1-9 
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Opioids ; Narcotic antagonists ; Phencyclidine ; Cyclazocine ; Naltrexone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To assess the commonalities and differences in the discriminative stimulus properties of phencyclidine (PCP) and psychotomimetic opioids, rats were trained to discriminate PCP (2.0 mg/kg), cyclazocine (1.0 mg/kg), and saline in a three-choice discrete-trial avoidance paradigm. Stimulus control of behavior, defined as the reliable completion of 18 trials of a 20-trial session on the appropriate choice lever after administration of PCP, cyclazocine, or saline, was established in an average of 157 sessions. In tests of stimulus generalization, SKF-10,047 and dextrorphan engendered lever choices appropriate to both PCP and cyclazocine, sometimes in the same animal and at the same dose. The rats responded almost exclusively on the PCP-appropriate lever after ketamine and on the saline lever after morphine and d-amphetamine, indicating pharmacologic specificity. Naltrexone, in doses that had little effect on stimulus control of behavior by PCP, completely blocked cyclazocine-like stimulus control. Decreases in cyclazocine choices in the presence of naltrexone were associated with increases in PCP choices. These results support conclusions derived from two-choice procedures that psychotomimetic opioids have PCP-like stimulus effects, and provide direct evidence that these effects of cyclazocine are mediated by a component of action insensitive to an opiate antagonist.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2072
    Keywords: Diprenorphine ; Naloxone ; Ketocyclazocine ; Ethylketocyclazocine ; Opiate antagonist ; κ-Receptor ; Punishment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of naloxone and diprenorphine, opiate antagonists with different receptor-binding properties, and the putative κ-receptor agonists, ketocyclazocine and ethyl-ketocyclazocine (EKC), were studied on food-reinforced responding in rats. Behavior was maintained under a multiple-component 1-min variable-interval schedule in which 12-min periods of unpunished responding alternated with 4-min periods in which each response was punished by a brief electric footshock. Daily sessions were 1 h. Naloxone (0.01–10 mg/kg) decreased unpunished responding only slightly; punished responding was decreased significantly to 66% of control by 10 mg/kg. Diprenorphine (0.01–10 mg/kg) did not affect unpublished responding and increased punished responding dose-dependently to as much as 190% of control. EKC (0.01–1.0 mg/kg) decreased unpunished and punished responding dose-dependently and comparably, whereas ketocyclazocine (0.01–1.0 mg/kg)decreased unpublished responding but did not significantly affect punished responding. Diprenorphine was more potent than naloxone in blocking the decreases in responding produced by the κ agonists. Differences in the behavioral effects of naloxone and diprenorphine appear to reflect the different receptor-binding properties of the two opiate antagonists.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 114 (1994), S. 215-224 
    ISSN: 1432-2072
    Keywords: Amphetamine ; Cocaine ; Opioid antagonist ; Naloxone ; Catecholamine uptake inhibitors ; Catecholamine releasing agents ; Psychomotor stimulants ; Motor activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Naloxone, an opioid receptor antagonist, attenuates a wide range of behavioral effects ofd-amphetamine, such as the stimulation of motor activity. To investigate the pharmacological selectivity of the naloxone/amphetamine interaction, we assessed the effects of naloxone (5.0 mg/kg SC) upon motor activity induced in rats by a range of psychomotor stimulant drugs with a mechanism of action either similar to or different from that ofd-amphetamine. Each of the drugs tested caused dose-dependent increases in both gross and fine activity. Naloxone attenuated the gross but not the fine activity response tod- andl-amphetamine, but had no influence upon the other catecholamine-releasing drugs, methamphetamine and phendimetrazine. In contrast, naloxone increased the gross but not the fine activity response to the catecholamine uptake inhibitors cocaine and mazindol, but had no effects upon the motor response to methylphenidate. The responses to other stimulant drugs (apomorphine, caffeine, scopolamine) were unaffected by naloxone pretreatment. The present findings extend the range of conditions under which naloxone and, by inference, endogenous opioid systems, modulate the behavioral response to psychomotor stimulants. However, the differential effects of naloxone upon the motor response to individual stimulant drugs support previous suggestions of fundamental differences in mechanisms of action among these compounds.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 63 (1979), S. 207-209 
    ISSN: 1432-2072
    Keywords: d-Amphetamine ; Chlorpromazine ; Naloxone ; Avoidance behavior
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Lever-pressing by squirrel monkeys was maintained under a continuous avoidance schedule in which each response postponed for 30 s the delivery of an electric shock to the tail. Dose-response curves were determined for chlorpromazine (0.03–0.3 mg/kg) and d-amphetamine (0.03–1.0 mg/kg) administered alone and administered concomitantly with 1.0 or 10 mg/kg of aaloxone. The dose-response curves for chlorpromazine and d-amphetamine were similar to those previously reported for monkeys under other schedules of shock-maintained behavior: Chlorpromazine decreased responding in a dose-related manner while d-amphetamine increased responding at low doses and disrupted behavior at the highest dose. Naloxone did not modify the effects of chlorpromazine, and d-amphetamine. These results suggest that interactions observed previously between naloxone and nonopiate drugs on behavior in pigeons and rodents are not general phenomena in all animal species.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 39 (1974), S. 23-37 
    ISSN: 1432-2072
    Keywords: Morphine ; Pentazocine ; Avoidance Behavior ; Tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Dose-response curves were determined for the effects of morphine (0.3–10 mg/kg) and pentazocine (1.0–30 mg/kg) on continuous avoidance responding in the rat. Each dose of morphine was retested following 3 days of morphine administration. The pentazocine curve was redetermined after 3 days of treatment with either pentazocine or morphine. Upon initial testing, morphine and pentazocine both generated biphasic dose-response curves. Graded increases in response rate were produced by 0.3–3.0 mg/kg of morphine and by 1.0–10 mg/kg of pentacozine; behavior was disrupted by 10 mg/kg of morphine and by 30 mg/kg of pentazocine. The stimulant effects of the lower doses of morphine and pentazocine were markedly reduced by 3 days of drug treatment; the disruptive effect of the highest dose of each drug was similarly attenuated. These findings show that tolerance can develop to a stimulant component of action of morphine and pentazocine in the rat. The development of pentazocine cross-tolerance to morphine provides additional support for the view that a common mechanism mediates the effects of morphine and pentazocine on avoidance behavior.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 34 (1974), S. 135-142 
    ISSN: 1432-2072
    Keywords: Profadol ; Naloxone ; Avoidance Behavior ; Locomotor Activity ; Narcotic Antagonists
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of profadol, an analgesic with mixed agonist and antagonist properties, were evaluated on continuous avoidance responding and locomotor activity in the rat. Profadol was tested alone and concomitantly with 8.0 mg/kg of naloxone. Profadol had a biphasic effect on avoidance response rate, increasing it at from 0.5–8.0 mg/kg and decreasing it at 32 mg/kg. Naloxone blocked both the rate increasing and the rate decreasing effects of profadol on avoidance responding. Locomotor activity was unaffected by 0.5–64 mg/kg of profadol alone, but was increased when profadol and naloxone were administered together. These findings extend the dual action hypothesis for morphine to a partial morphine agonist. This study provides further evidence that the behavioral activity of narcotic antagonists can be evaluated in the rat in an objective and quantitative manner.
    Type of Medium: Electronic Resource
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