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  • Place conditioning  (4)
  • Rats  (3)
  • 1
    Digitale Medien
    Digitale Medien
    β-Endorphin-(1-27) is a naturally occurring antagonist of the reinforcing effects of opioids (1988)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 338 (1988), S. 392-396 
    Details
    ISSN: 1432-1912
    Schlagwort(e): β-Endorphin-(1-27) ; Opioids ; Place conditioning ; β-Endorphin ; μ-, δ-, κ-, ε-Receptors ; Motivation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00172115
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  • 2
    Digitale Medien
    Digitale Medien
    Tolerance and selective cross-tolerance to the motivational effects of opioids (1988)
    Springer
    Psychopharmacology 96 (1988), S. 110-115 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Tolerance ; Opioids ; Reinforcement ; Place conditioning ; Morphine ; U-69593 ; d-Amphetamine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02431542
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  • 3
    Digitale Medien
    Digitale Medien
    Evidence that the aversive effects of opioid antagonists and κ-agonists are centrally mediated (1989)
    Springer
    Psychopharmacology 98 (1989), S. 203-206 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Place conditioning ; Motivation ; Aversion ; Opioids, μ-, δ- and κ-receptors ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00444692
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  • 4
    Digitale Medien
    Digitale Medien
    Neuroanatomical substrates mediating the aversive effects of D-1 dopamine receptor antagonists (1991)
    Springer
    Psychopharmacology 103 (1991), S. 209-214 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Place conditioning ; SCH-23390 ; A-69024 ; D-1 receptor ; N. accumbens ; Mesolimbic system ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02244205
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  • 5
    Digitale Medien
    Digitale Medien
    Development of physical dependence on morphine in respect to time and dosage and quantification of the precipitated withdrawal syndrome in rats (1973)
    Springer
    Psychopharmacology 33 (1973), S. 19-38 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Development of Morphine Dependence ; Precipitated Withdrawal ; Rats
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In rats implanted subcutaneously with morphine containing pellets different degrees of dependence were induced by varying the dosage, frequency of implantation and duration of exposure to morphine. Withdrawal was precipitated by intraperitoneal injection of morphine antagonists, mostly levallorphan. The absorption of morphine from the subcutaneous depots was estimated chemically. When withdrawal was precipitated with a constant dose of antagonist the frequency of occurrence of various counted signs and the presence of some checked signs were studied in respect to varying degrees of dependence. The results were compared to those obtained after administration of increasing doses of antagonist in groups of animals that had developed a constant degree of dependence. In both types of experiments the results were rather similar. Some signs became progressively more pronounced when dependence got stronger or the dose of the antagonist was increased. In contrast, other signs showed a maximal frequency at the lower degrees of dependence or after administration of the lower doses of antagonist and decreased or even disappeared when the degree of dependence was higher or the dose of antagonist further increased. Obviously, in withdrawal the intensity of “recessive” signs like writhing and wet dog shaking declines when “dominant” signs like jumping, flying (a vigorous kind of jumping) and teeth chattering increase. An inverse relationship between the occurrence of various signs could also be shown within the 30 min observation period. Changes in the integrative mechanisms controlling behaviour during withdrawal are supposed to be the reason for this shift of signs. In other experiments in which the interval between each morphine implantation was prolonged the frequency of some signs like jumping and teeth chattering tented to plateau. This finding seems to be correlated to some kind of steady state on resorption of morphine from the subcutaneous depots, as was found in chemical analysis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00428791
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  • 6
    Digitale Medien
    Digitale Medien
    Role of catecholaminergic mechanisms in the expression of the morphine abstinence syndrome in rats (1974)
    Springer
    Psychopharmacology 39 (1974), S. 121-143 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Expression of Morphine Withdrawal ; Catecholaminergic Mechanisms ; Rats
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effect of various drugs affecting catecholaminergic mechanisms on the precipitated morphine withdrawal syndrome was studied in rats which had developed a medium degree of dependence. Administration of low doses of d-amphetamine, cocaine, and L-Dopa shortly before precipitating withdrawal by levallorphan induced a dose-dependent increase of “dominant” withdrawal signs such as jumping and a decrease of “recessive” signs such as wet dog shaking; signs such as diarrhea and ptosis decreased, whereas rhinorrhea, salivation and lacrimation increased. A qualitatively very similar change in withdrawal signs occurred when withdrawal was precipitated in extremely highly dependent rats and/or increasing doses of the antagonist were administered. Therefore, the effects of the above drugs are interpreted as potentiation of withdrawal. Pretreatment with higher doses of the same drugs provoked strong stereotyped behaviour which obviously suppressed the occurrence of other motor signs. Activation of noradrenergic or dopaminergic mechanisms with desipramine or apomorphine induced an increase in the intensity of withdrawal, which was, however, much more pronounced after the former than the latter drug. When catecholamines (CA) were previously depleted by alpha-methyl-para-tyrosine (AMT), apomorphine lost a great part of its effectiveness. Blockade of CA synthesis by AMT alone resulted in decreased jumping while at the same time writhing largely increased, thus, inducing a profile of signs characteristic for a weak withdrawal. Selective inhibition of noradrenaline synthesis by FLA-63 resulted in a reduction in withdrawal intensity. Ro 4-4602 + L-Dopa, given after AMT, antagonized and reversed the reduction of withdrawal, but this effect was not so pronounced when by additional pretreatment with FLA-63 NA levels remained low. It is concluded that of both brain CA especially noradrenaline is involved in the manifestation of the morphine withdrawal syndrome.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00440843
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  • 7
    Digitale Medien
    Digitale Medien
    Comparison of withdrawal precipitating properties of various morphine antagonists and partial agonists in relation to their stereospecific binding to brain homogenates (1976)
    Springer
    Psychopharmacology 46 (1976), S. 41-51 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Precipitated morphine withdrawal ; Morphine antagonists and partial agonists ; Stereospecific opiate binding ; Rats
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In morphine-dependent rats the withdrawal precipitating properties of various morphine antagonists and partial agonists were studied by quantitatively evaluating a variety of different withdrawal signs. A comparison of the dose response curves of the various substances obtained for the different signs revealed marked differences in respect to the lowest effective doses (EDs) necessary to precipitate the withdrawal signs as well as in the maximum frequencies of the signs induced. The “pure” antagonist, naloxone, which was judged very potent according to the ED, precipitated the lowest levels of jumping, whereas certain partial agonists of the benzomorphane type, which were less potent according to the ED, induced very high levels of this sign. These latter compounds, however, failed to precipitate “complete” withdrawal, as evidenced by the nearly complete absence of some of the withdrawal signs. The jumping precipitating potency of the antagonists as judged from the ED was found to be highly correlated to the stereospecific binding of these substances to rat brain homogenate. On the other hand, the ability of the substances to precipitate high levels of jumping was seen to increase, at least within a certain range, with increasing degree of agonistic properties, as indicated by the ratio of stereospecific binding in the presence and absence of sodium.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00421548
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