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  • 1
    Electronic Resource
    Electronic Resource
    Oxford UK : Blackwell Science Ltd.
    Journal of neurochemistry 74 (2000), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:κ-Opioid receptor agonists prevent alterations indopamine neurotransmission that occur in response to repeated cocaineadministration. The present microdialysis study examined whetheradministration of the selective κ-opioid receptor agonist U69593 withmethamphetamine prevents alterations in dopamine levels produced by neurotoxicdoses of methamphetamine. Swiss Webster mice were injected intraperitoneallywith methamphetamine (10.0 mg/kg) or saline, four times in 1 day, at 2-hintervals. Prior to the first and third injection, they received U69593 (0.32mg/kg s.c.) or vehicle. Microdialysis was conducted 3, 7, or 21 days later.Basal and K+-evoked (60 and 100 mM) dopamine overflow werereduced 3 days after methamphetamine administration. These effects werelong-lasting in that they were still apparent 7 and 21 days aftermethamphetamine treatment. Intrastriatal (5.0 and 50 μM) orsystemic (1.0-10.0 mg/kg) administration of methamphetamine increased dopamineconcentrations in control animals. In mice preexposed to methamphetamine,methamphetamine-evoked dopamine overflow was reduced. In animals that hadreceived methamphetamine with U69593, basal dopamine levels did not differfrom those of vehicle-treated controls. U69593 treatment attenuated thedecrease in K+-evoked dopamine produced by prior methamphetamine exposure. The reduction in methamphetamine-evoked dopamine levels was also attenuated. The administration of U69593 alone did not modify basal or stimulus-evoked dopamine levels. These data demonstrate that repeated methamphetamine administration reduces presynaptic dopamine neuronal function in mouse striatum and that co-administration of a selective κ-opioid receptor agonist with methamphetamine attenuates these effects. U69593 treatment did not modify the hyperthermic effects of methamphetamine, indicating that this κ-opioid receptor agonist selectively attenuates methamphetamine-induced alterations in dopamine neurotransmission.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford UK : Blackwell Science Ltd.
    Journal of neurochemistry 75 (2000), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract : The behavioral effects of cocaine are enhanced following constitutive deletion of the serotonin1B receptor. The neural substrates mediating the enhanced response to cocaine are unknown. The present studies determined whether basal dopamine dynamics or cocaine-evoked dopamine levels are altered in projection areas of mesostriatal or mesoaccumbens dopamine neurons following serotonin1B receptor deletion. Male wild-type and serotonin1B knockout mice were implanted with microdialysis guide cannulas aimed at the dorsal striatum or nucleus accumbens. The zero net flux method of quantitative microdialysis was used to quantify basal extracellular dopamine concentrations (DAext) and the extraction fraction of dopamine (Ed), which provides an index of dopamine uptake. Conventional microdialysis techniques were used to quantify cocaine (0, 5.0, and 20.0 mg/kg)-evoked dopamine overflow. Basal DAext and Ed did not differ in striatum of wild-type and knockout mice. Similarly, cocaine-stimulated dopamine overflow did not differ between genotype. The basal Ed did not differ in the nucleus accumbens of wild-type and knockout mice. However, DAext was significantly elevated in the nucleus accumbens of knockout mice. Cocaine-evoked dopamine overflow (nM) was also enhanced in the nucleus accumbens of knockout mice. However, the cocaine-induced increase in dopamine levels, relative to basal values, did not differ between genotype. These data demonstrate that deletion of the serotonin1B receptor is associated with increases in basal DAext in the nucleus accumbens. This increase is not associated with an alteration in Ed, suggesting increased basal dopamine release in these animals. It is hypothesized that these alterations in presynaptic neuronal activity are a compensatory response to constitutive deletion of the serotonin1B receptor and may contribute to the enhanced behavioral effects of psychostimulants observed in knockout mice.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 81 (2002), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: An involvement of the D3 dopamine receptor in the regulation of extracellular dopamine has been suggested. However, the mechanisms mediating this effect are unclear. We have used the technique of no net flux microdialysis under transient conditions to examine the influence of the D3-preferring agonist (+)-PD128907 upon extracellular dopamine levels in the nucleus accumbens of the mouse. (+)-PD 128907 (0.1 mg/kg intraperitoneally) significantly decreased extracellular dopamine. This decrease was associated with a marked increase in the extraction fraction, which suggests an increase in dopamine clearance. The ability of D3-preferring compounds to modulate dopamine uptake was investigated in vitro using rotating disk electrode voltammetry. (+)-PD 128907 (10 nm) significantly increased the initial clearance rate of 3 μm dopamine in rat nucleus accumbens tissue suspensions. Kinetic analysis revealed no change in the apparent Km of uptake but it showed a 33% increase in Vmax. In contrast, the D3 antagonist GR 103691 (10 nm) significantly decreased dopamine uptake. Consistent with the low levels of D3 receptors in the dorsal striatum, neither compound affected uptake in tissue suspensions from this brain region. These data indicate that D3 receptor activation increases dopamine uptake in the nucleus accumbens and suggest that this receptor subtype can regulate extracellular dopamine by modulating the DA transporter activity.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: Tolerance ; Opioids ; Reinforcement ; Place conditioning ; Morphine ; U-69593 ; d-Amphetamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The issue of whether tolerance develops to the motivational effects of opioids was addressed by use of an unbiased place preference conditioning procedure. Administration of the μ-opioid agonists morphine or fentanyl produced dose-related preferences for the drug-associated place in control rats. In contrast, the κ-opioid agonist, U-69593 produced conditioned place aversions. Non-contingent administration of morphine (5.0 mg/kg/12 h) for 4 days prior to conditioning resulted in tolerance to its reinforcing effects, and cross-tolerance to the effects of fentanyl. No cross-tolerance to the motivational effects of the psychostimulantd-amphetamine or the κ-opioid agonist U-69593 was observed. Chronic administration of U-69593 prior to conditioning produced tolerance to its aversive effects. This treatment did not, however, modify the reinforcement produced by morphine. These data demonstrate that tolerance develops to both the reinforcing and aversive properties of opioids and suggest that differential cross-tolerance may provide a useful method for determining the pharmacological basis underlying drug-induced motivational effects.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 98 (1989), S. 203-206 
    ISSN: 1432-2072
    Keywords: Place conditioning ; Motivation ; Aversion ; Opioids, μ-, δ- and κ-receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The role of central versus peripheral opioid receptors in mediating the aversive effects of opioids was examined by use of an unbiased place preference conditioning procedure in rats. The non-selective opioid antagonist naloxone (NLX) produced conditioned aversions for the drug-associated place after subcutaneous (SC) as well as intracerebroventricular (ICV) administration. Place aversions were also observed in response to the ICV administration of the selective μ-antagonist CTOP. In contrast, the selective δ-antagonist ICI 174,864 and the selective κ-antagonist norbinaltorphimine (nor-BNI) (ICV) were without effect. Place aversions were also produced by central applications of the selective κ-agonist U50,488H and the dynorphin derivative E-2078. For those opioid ligands tested, the doses required to produce place aversions were substantially lower following ICV as compared to SC administration. These data confirm that κ-agonists and opioid antagonists produce aversive states in the drug-naive animal and demonstrate that this effect is centrally mediated. Furthermore, the ability of NLX and CTOP, in contrast to both ICI 174,864 and nor-BNI, to produce place aversions suggests that the aversive effects of opioid antagonists result from the blockade of μ-receptors.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 338 (1988), S. 392-396 
    ISSN: 1432-1912
    Keywords: β-Endorphin-(1-27) ; Opioids ; Place conditioning ; β-Endorphin ; μ-, δ-, κ-, ε-Receptors ; Motivation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A place preference conditioning procedure was used to characterize the motivational effects of β-endorphin-(1-27), a naturally occurring fragment of β-endorphin (β-EP). The intracerebroventricular (ICV) administration of β-EP, selective μ-(DAGO) or δ-(DPDPE) opioid receptor agonists to rats produced marked preferences for the drug-associated place, whereas the selective κ-opioid receptor agonist, U-50488H produced conditioned aversions. ICV injections of the β-EP-(1-27) (5–20 μg), however, resulted in no preference for either the drug- or vehicle-associated place. Pretreatment with β-EP-(1-27) (10 μg) eliminated the place preference produced by β-EP. It abolished the place preferences induced by both DAGO and DPDPE but did not modify the effects of either U-50488H or the psychostimulant d-amphetamine. These data demonstrate that β-EP-(1-27) selectively antagonizes the motivational effects of μ- and β-opioid agonists and suggest that this fragment may function as an endogenous antagonist of the reinforcing effects of opioid agonists in vivo.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 117 (1995), S. 240-247 
    ISSN: 1432-2072
    Keywords: Microdialysis Conditioned place preference ; Morphine Locomotor activity ; Genetic differences ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Studies examining differential sensitivity to psychoactive drugs in mice suggest that genotype may play a critical role. Furthermore, an involvement of genotype in mediating individual differences in sensitivity to the rewarding effects of several drugs of abuse has also been postulated. The aim of this study was to examine the conditioned rewarding and dopamine-releasing effects of morphine in two outbred rat strains commonly used in addiction research. Additionally, the behavioural and neuroendocrine responses of these strains to the stress of novelty were also examined. Basal locomotor activity was higher in Wistar rats than Sprague-Dawley following exposure to a novel environment. In contrast, elevations in plasma corticosteroid levels following novelty exposure did not differ between the two strains. In a counterbalanced place preference conditioning procedure, increasing doses of morphine (1.0–10.0 mg/kg SC) produced significant conditioned place preferences (CPP) in both Wistar and Sprague-Dawley strains. However, Wistar rats required a significantly larger dose of morphine (5.0 mg/kg) to produce a significant CPP than the Sprague-Dawley rats. In the latter strain, CPP occurred with doses of 3.0 mg/kg and greater. In parallel microdialysis experiments, both strains showed significant dose-related increases in dopamine release in the nucleus accumbens following acute morphine challenge (1.0–10.0 mg/kg SC). Again in Wistar rats, a larger dose of morphine was necessary to produce a significant increase in comparison to Sprague-Dawley rats. These results show that genetically distinct rat strains can show differential sensitivity to opioids, more specifically to drug-seeking responses.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-2072
    Keywords: Place conditioning ; SCH-23390 ; A-69024 ; D-1 receptor ; N. accumbens ; Mesolimbic system ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An unbiased place preference conditioning procedure was used to examine the secondary reinforcing effects of selective D-1 dopamine (DA) receptor antagonists and the neuroanatomical substrates mediating these effects. Systemic administration of SCH-23390 or the non-benzazepine D-1 receptor antagonist A-69024 produced dose-related conditioned aversions for the drug-associated place. In contrast, the D-2 antagonists spiperone and (−)sulpiride were without effect. SCH-23390-induced place aversions were also observed after intracerebroventricular administration. The minimum dose producing this effect was significantly lower than that after systemic injection. Aversive effects were also observed after microinjection of SCH-23390 into the n. accumbens. In contrast, microinjections of this antagonist into the ventral tegmental area, caudate putamen or medial prefrontal cortex were without effect. These data confirm that the blockade of D-1 but not D-2 DA receptors induces aversive states. Furthermore, they suggest that D-1 receptors in the n. accumbens may play an important role in the regulation of non-drug induced affective states.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 147 (1999), S. 33-34 
    ISSN: 1432-2072
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-2072
    Keywords: Cocaine ; Self-administration ; Place preference conditioningδ-opioid receptors ; Naltrindole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The non-selective opioid antagonist naltrexone and the partial agonist buprenorphine have been reported to reduce cocaine self-administration (SA) and relapse in both humans and rhesus monkeys. Data suggesting an involvement ofδ-opioid receptors in modulating the conditioned rewarding effects of cocaine were also recently presented. In view of such findings, the present SA and place conditioning studies were conducted to examine the influence of the selectiveδ-opioid receptor antagonist naltrindole upon the rewarding effects of cocaine. Sprague-Dawley rats were trained to self-administer cocaine (1.0 mg/kg per infusion) on an FR2 schedule of reinforcement. Dose-response and antagonist testing commenced once stable rates of cocaine SA were achieved. For antagonist testing, rats received naltrindole (0.03–10.0 mg/kg, IP) 30 min prior to the start of 2-h SA sessions. SA behavior in response to cocaine delivery (0.25 and 1.0 mg/kg per infusion) was then determined. Naltrindole in doses of 0.03–3.0 mg/kg did not alter the number of cocaine infusions taken by the rats. A higher dose of naltrindole (10.0 mg/kg), which markedly depressed locomotor activity, resulted in a 16% reduction of cocaine (0.25 mg/kg per infusion) SA behavior. When SA sessions were terminated and naltrindole (1.0 mg/kg) was administered repeatedly for 3 days, no alterations in the re-acquisition of cocaine SA were seen. Place conditioning studies also failed to find an effect of naltrindole (0.1–3.0 mg/kg) on cocaine (10 mg/kg) — induced conditioned place preferences. Naltrindole, by itself, did not induce significant place conditioning. These data fail to indicate a role ofδ-opioid receptors in modulating either the positive reinforcing or conditioned rewarding effects of cocaine. Furthermore, they suggest that the therapeutic actions of naloxone, naltrexone and buprenorphine on cocaine SA behavior may not result from the specific blockade ofδ-opioid receptors.
    Type of Medium: Electronic Resource
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