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  • 1
    Electronic Resource
    Electronic Resource
    Effects of d-amphetamine, morphine, naloxone, and drug combinations on visual discrimination in rats (1988)
    Springer
    Psychopharmacology 94 (1988), S. 172-177 
    Details
    ISSN: 1432-2072
    Keywords: Rats ; Visual discrimination ; Morphine ; Amphetamine ; Naloxone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of d-amphetamine, morphine, and naloxone on visual discrimination were investigated using a two-choice discrete-trial procedure in which rats were trained to discriminate the position of a lightflash. Morphine (0.3–5.6 mg/kg) but not amphetamine (0.1–1.0 mg/kg) caused a significant dose-dependent disruption in discriminative performance. Both amphetamine and morphine increased response latencies. Naloxone (1.0 mg/kg) prevented the disruption of any aspect of performance by up to 100 mg/kg morphine. Performance after naloxone/amphetamine co-administration was not significantly different from that observed after amphetamine alone. Naloxone alone (0.3–10 mg/kg) had no effect on discrimination, spatial bias or response latencies. These results suggest that morphine and amphetamine affect different components of discrimination performance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00176840
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  • 2
    Electronic Resource
    Electronic Resource
    Suppression of deprivation-induced water intake in the rat by opioid antagonists: central sites of action (1987)
    Springer
    Psychopharmacology 91 (1987), S. 279-284 
    Details
    ISSN: 1432-2072
    Keywords: Naltrexone methobromide ; Water intake ; Paraventricular hypothalamic nucleus ; Supraoptic hypothalamic nucleus ; Opiate antagonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of naltrexone methobromide, a quaternary derivative of the opioid antagonist naltrexone, were investigated on deprivation (24 h)-induced water intake in the unilaterally cannulated rats. Naltrexone methobromide reduced post-deprivational water intake with an ED50 of 7.3 μg when tested at 30 min (peak effect) after intracere-broventricular administration. It also dose-dependently (0.3–10 μg) depressed water intake, with peak effects at 15 min, after microinjection into the paraventricular hypothalamic nucleus and into the supraoptic hypothalamic nucleus. The drug did not produce any other effects on behaviors. The ED50s were 1.4 μg when given into the paraventricular nucleus, and 3.3 μg when given into the supraoptic nucleus, respectively. Although injections of higher doses (1.0, 3.0 and/or 10 μg) of the drug into the preoptic area, zona incerta, and corpus callosum significantly suppressed water intake, other behavioral manifestations, such as rotational behaviors, convulsions, body shakes, head swaying, and/or backward locomotion were manifested simultaneously with the reduction in drinking. When injected into the lateral hypothalamic area, water intake was not significantly affected by the drug. These findings suggest that the paraventricular and supraoptic hypothalamic nuclei are important sites of action in the naltrexone-induced suppression of water intake.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00518177
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  • 3
    Electronic Resource
    Electronic Resource
    Pharmacologic specificity of tolerance to caffeine-induced stimulation of locomotor activity (1987)
    Springer
    Psychopharmacology 93 (1987), S. 428-434 
    Details
    ISSN: 1432-2072
    Keywords: Caffeine ; Tolerance ; Locomotor activity ; Methylxanthines ; Psychomotor stimulants ; Amphetamine ; Adenosine analogs ; Drug withdrawal ; Cross-tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pharmacologic specificity of tolerance to caffeine-induced stimulation of locomotor activity was studied in adult male rats that were given access to either caffeine solution (0.5 or 1.0 mg/ml) or plain water for 10 min every 6 h on a chronic daily basis; daily caffeine intake averaged 41 and 62 mg/kg, respectively. Dose-effect curves were determined for behavioral stimulant and depressant drugs in control and caffeine-treated groups. Drugs were injected IP and locomotor activity was measured for 30 min beginning 35 min later. Rats tolerant to stimulation of locomotor activity by caffeine were also tolerant to theophylline and 7-(2-chloroethyl)theophylline, but not to any of six nonxanthine stimulants, including cocaine, methylphenidate, and d-amphetamine. The adenosine analogs, R(−)-N6-2-(phenylisopropyl)adenosine(R(−)-PIA) and 5′-(N-ethyl)carboxamidoadenosine (NECA), decreased locomotor activity of control and caffeine-treated (0.5 mg/ml) rats; dose-effect curves in rats consuming caffeine chronically were displaced to the right of the control curves by 10-fold for R(−)-PIA and 100-fold for NECA. Dose-effect curves for the nonadenosine behavioral depressants chlorpromazine and diazepam were unchanged by chronic treatment with caffeine, but the curve for pentobarbital, which is thought to inhibit adenosine receptor binding, was shifted to the right by a factor of 3. Rats withdrawn from chronic caffeine for 24 h were still completely tolerant to caffeine-induced stimulation of locomotor activity. Dose-effect curves for R(−)-PIA and d-amphetamine in rats withdrawn from chronic caffeine for 24 h were not different from curves in control animals. These results indicate that tolerance to caffeine-induced stimulation of locomotor activity is specific to the methylxanthine class of stimulants and is not a property of nonxanthine psychomotor stimulants. Furthermore, the adenosine-antagonist activity of caffeine remains evident even in rats completely tolerant to the stimulant effect of caffeine. These results provide no support for the view that caffeine tolerance is due to enhanced sensitivity of central adenosine systems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00207230
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  • 4
    Electronic Resource
    Electronic Resource
    Acute opioid but not benzodiazepine dependence in rats responding for intracranial self-stimulation (2000)
    Springer
    Psychopharmacology 148 (2000), S. 263-271 
    Details
    ISSN: 1432-2072
    Keywords: Key words Benzodiazepine ; Chlordiazepoxide ; Diazepam ; Flumazenil ; Intracranial self-stimulation (ICSS) ; Morphine ; Naltrexone ; Opioid ; Progressive ratio
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Four-hour pretreatment with a single dose of morphine or related opioids sensitizes rats responding for intracranial self-stimulation (ICSS) to the rate-decreasing effect of naltrexone, indicative of antagonist-precipitated withdrawal from acute opioid dependence. Objectives: To determine whether sensitization to naltrexone could be observed in morphine-pretreated rats responding under a progressive ratio (PR) schedule of ICSS and to determine whether acute pretreatment with benzodiazepines produces similar sensitization to flumazenil. Methods: Rats with an electrode in the medial forebrain bundle were trained to respond under an ICSS PR schedule, in which the number of responses required for a 250-ms stimulus started at one, then increased gradually. If no responding occurred for 30 s, the response requirement reverted to a single response and the break point was operationally defined. Results: Pretreatment (4-h) with 3.0 mg/kg or 5.6 mg/kg morphine reduced the ED25 values of naltrexone for decreasing response rate from 18±6.7 mg/kg to 0.021±0.006 mg/kg and 0.006±0.001 mg/kg, respectively. Changes in break point usually paralleled changes in response rate. In contrast, 4- to 24-h pretreatment with the benzodiazepines chlordiazepoxide (30 mg/kg and 100 mg/kg) or diazepam (3.0 mg/kg and 10 mg/kg), behaviorally-active doses, did not significantly alter sensitivity to the effects of flumazenil (1.0–30 mg/kg). Conclusions: These results show that PR ICSS provides a stable behavioral baseline for testing drugs in rats and extend to this procedure the generality of the phenomenon of acute opioid dependence. There was no comparable evidence of acute benzodiazepine dependence, suggesting that there are differences in the ways that opioid and benzodiazepine agonists initiate the adaptive changes that underlie the state of physical dependence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050050
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  • 5
    Electronic Resource
    Electronic Resource
    Morphine-like discriminative stimulus effects of opioid peptides: possible modulatory role ofd-Ala2-d-Leu5-enkephalin (DADL) and dynorphin A(1-13) (1988)
    Springer
    Psychopharmacology 94 (1988), S. 32-37 
    Details
    ISSN: 1432-2072
    Keywords: Opioid peptides ; Discriminative stimulus effects ; Opioid receptor subtypes ; Morphine ; Dynorphin A(1-13) ; d-Ala2-d-Leu5-enkephalin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The role of the different opioid receptors was studied in rats trained to discriminate SC injections of 3.0 mg/kg morphine from saline by tests for generalization to graded doses of morphine and receptor-selective peptides administered into the lateral cerebral ventricle. Dose-dependent morphine-like stimulus effects were produced over a wide range of doses (0.001–30 μg), depending upon ligand and animal, by morphine, by themu-selective peptides DAGO[d-Ala2-NMePhe4-Gly(ol)-enkephalin] and FK33824[d-Ala2,NMePhe4-Met(O)5-(ol)-enkephalin], and by thedelta-selective peptide, DADL[d-Ala2,d-Leu5enkephalin]. The order of relative potency of these substances was: FK33824〉DAGO〉morphine〉DADL. In contrast, DPLPE[d-Pen2,l-Pen5)enkephalin], which has much greaterdelta receptor selectivity than does DADL, and dynorphin A(1-13) (0.1–10 μg), akappa-receptor agonist, engendered choice responding appropriate for saline. When 1.0 μg DADL, a dose lacking morphine-like discriminative effects, was administered concurrently with SC morphine, the stimulus effects of morphine were potentiated. Concurrent administration of 10 μg dynorphin A(1-13) and morphine attenuated the stimulus effects of morphine inconsistently. These results support previous findings thatmu-opioid receptors are of primary importance in mediating the morphine-like discriminative effects of opioid peptides. They also suggest that morphine-like discriminative effects can be modulated by other types of opioid receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00735877
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