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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 83 (1984), S. 257-261 
    ISSN: 1432-2072
    Schlagwort(e): Drug discrimination ; Reinforcement variables ; Fentanyl ; Morphine ; Sufentanil ; Naloxone ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rats were trained to discriminate between fentanyl (0.04 mg/kg) and saline in a two-lever procedure. Using a FR 10 schedule of food reinforcement, drug-induced differences between the number of reinforcers obtained under fentanyl and saline conditions were observed. The effect of eliminating these differences on the outcome of generalization tests was investigated by different manipulations. In one group (N=10), the FR 10 schedule used during saline sessions was changed to FR 6 during drug sessions. In a second group (N=12), saline sessions ended after the number of reinforcers obtained was equal to the number obtained during the preceding drug session. A control group (N=10) was trained using a FR 10 schedule under both conditions. Elimination of differences in reinforcement frequency 1) accelerated the acquisition of the discrimination, 2) diminished response bias, 3) flattened the slope and reduced the ED50 value of generalization gradients of fentanyl, morphine and sufentanil and 4) increased the ED50 value of naloxone in antagonizing 0.04 mg/kg fentanyl. It is concluded that the unconditioned effects of 0.04 mg/kg fentanyl on response rate in a FR 10 procedure lead to differences between saline and drug sessions which contribute to the apparent discriminative stimulus properties of fentanyl.
    Materialart: Digitale Medien
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 76 (1982), S. 149-156 
    ISSN: 1432-2072
    Schlagwort(e): Drug discrimination ; Drug generalization ; Fentanyl ; Morphine ; Amphetamine ; Nicotine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Different groups of rats were trained to discriminate fentanyl (F) (0.03, 0.02, or 0.01 mg/kg) from saline or to discriminate 0.03 mg/kg fentanyl (F) from alternative stimulus conditions (saline, 0.15 mg/kg nicotine, or 0.01 mg/kg F). When percentage of responses on the drug lever and percentage of time spent responding on the drug lever were used as dependent variables, it was found that training dose and alternative stimulus condition both affected the ED50 and the slope of the F generalization gradient. ED50 and slope values based on group data were not significantly different from values based on individual data. Differences between the results of the first and second 2.5-min period of the extinction test were not significant. ED50 and slope values were unaffected by the preceding training session, except in the group trained to discriminate 0.03 from 0.01 mg/kg F. A lever selection measure showed a significant effect of alternative stimulus condition on ED50 values only. Training dose and alternative stimulus condition also affected the generalization to morphine. Under none of the conditions explored in this study did generalization occur to amphetamine or nicotine. The results are discussed in terms of the relative nature of drug generalization.
    Materialart: Digitale Medien
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  • 3
    ISSN: 1432-2072
    Schlagwort(e): Key words BTCP ; Cocaine ; Prazosin ; Monoamine re-uptake blocker ; Norepinephrine ; Dopamine ; Drug discrimination
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Rationale: Although both cocaine and the phencyclidine analog, BTCP, have dopamine (DA) re-uptake blocking properties, under some conditions their behavioral effects can be differentiated. Therefore, we examined whether the discriminative stimulus (DS) effects of BTCP are different from those of cocaine. Objectives: To compare the effects of monoamine re-uptake blockers, varying in their in vitro potencies as inhibitors of DA, norepinephrine (NE), or serotonin re-uptake, in different groups of rats trained to discriminate either BTCP or cocaine from saline. Additionally, drugs from other pharmacological classes were tested in both groups. Methods: Rats were trained to discriminate either BTCP (5 mg/kg, i.p.) or cocaine (10 mg/kg, i.p.) from saline under a two-lever FR10 drug discrimination procedure. Results: BTCP and cocaine cross-substituted in BTCP- and cocaine-trained rats. The DA re-uptake blockers, mazindol, indatraline, methylphenidate, GBR12909, and GBR12935, occasioned dose-related drug-lever (DL) selection both in cocaine- and in BTCP-trained rats, with potencies that were significantly correlated. In contrast, the NE re-uptake blockers, nisoxetine, desipramine, and nortriptyline, produced higher levels of DL selection in BTCP-trained rats than in cocaine-trained rats, a profile like that reported in low-dose cocaine-trained rats. Drugs from other classes acted similarly in both discriminations. Further, the α1-adrenergic antagonist prazosin dose dependently blocked the DS effects of the training dose of BTCP, but not of cocaine. Conclusions: Theresults suggest that the DS effects of BTCP are similar to cocaine, and resemble those of a low training dose of cocaine.
    Materialart: Digitale Medien
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  • 4
    ISSN: 1432-2072
    Schlagwort(e): Key words Schizophrenia ; Extrapyramidal side-effect ; Neuroleptic ; Antipsychotic ; Dopamine D2 receptor ; Serotonin 5-HT1A receptor ; Intrinsic activity ; Paw test ; Catalepsy ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rationale: Combining neuroleptics with 5-HT1A ligands is thought to improve the preclinical profile of neuroleptics and may be of interest in the development of new compounds that have greater therapeutic potential and/or are better tolerated. Objective: To examine 1) the ability of 5-HT1A ligands to alter the effects of neuroleptics in preclinical models for antipsychotic potential (hindlimb retraction time in the paw test) and extrapyramidal side-effects (forelimb retraction time in the paw test; catalepsy tests), 2) the role of intrinsic activity at 5-HT1A receptors in the modulatory effects of 5-HT1A ligands, and 3) the generality of the interactions across neuroleptics. Methods: The effects of different doses of 5-HT1A ligands with intrinsic activity ranging from high (e.g., 8-OH-DPAT) to low (e.g., WAY 100135) administered together with a fixed, high dose of the neuroleptics haloperidol, risperidone, and tropapride were examined in the paw test and on catalepsy. Results: Firstly, the 5-HT1A agonists 8-OH-DPAT and ipsapirone attenuated the extrapyramidal-like effects of haloperidol and risperidone more than their therapeutic-like effects; this was not observed for tropapride, where all of its effects were markedly attenuated. Secondly, neither the weak 5-HT1A agonist WAY 100135 nor the silent antagonist WAY 100635 attenuated the effects of neuroleptics. Thirdly, neuroleptics apparently differed in their sensitivity to interactions with 5-HT1A agonists inasmuch as 8-OH-DPAT and ipsapirone attenuated the effects of tropapride on hindlimb retraction times more than those of haloperidol or risperidone. Conclusions: The present data suggest that 5-HT1A agonists with intermediate or high, but not low, intrinsic activity may abolish the extrapyramidal effects of neuroleptics. Together with results of previous studies, it appears that 5-HT1A agonists alter the antipsychotic-like effects of neuroleptics, although this may depend on the neuroleptic studied.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 144 (1999), S. 405-410 
    ISSN: 1432-2072
    Schlagwort(e): Key words Conflict behavior ; Pigeon ; Anxiolytic ; Benzodiazepine partial allosteric agonist ; CGS 9896 ; ZK 95962 ; ZK 91296 ; Bretazenil ; Zolpidem ; Alpidem ; Imidazenil ; Abecarnil
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract   Rationale: Although all of the benzodiazepines in use for the treatment of anxiety are presumably full agonists, it is conceivable that partial benzodiazepine agonists may also be clinically effective on the basis of their effects in preclinical models of anxiety. Objectives: To compare the anxiolytic-like effects of different pharmacological/chemical classes of partial benzodiazepine agonists in the pigeon conflict procedure. Methods: Anticonflict effects in pigeons whose responding was maintained under a multiple FR30 food:FR30 food+shock schedule were characterized by 1) the magnitude of punished responding or 2) the percentage of pigeons (n=5–7/dose) showing significant increases in punished responding. Results: The partial allosteric modulators bretazenil and imidazenil produced anticonflict effects comparable with or superior to those observed following administration of the relatively full agonist midazolam. In contrast, neither the β-carbolines CGS 9896, ZK 95962 and ZK 91296, nor the imidazopyridines, alpidem and zolpidem, produced anticonflict effects comparable to either bretazenil and imidazenil or the relatively full benzodiazepine agonist, midazolam, at the doses examined in this study. Conclusions: Although the β-carboline ZK 95962 produced some anticonflict effects, none of the other compounds had anxiolytic-like effects like those observed with midazolam, bretazenil or imidazenil. However, because bretazenil and imidazenil produced robust anticonflict activity, the results indicate that partial allosteric modulators could have anxiolytic effects similar to those produced by higher efficacy compounds. Altogether, the results indicate that partial benzodiazepine agonists differ in their ability to produce robust anticonflict effects in the pigeon.
    Materialart: Digitale Medien
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  • 6
    ISSN: 1432-2072
    Schlagwort(e): Key words Schizophrenia ; Neuroleptics ; Dopamine D2 receptor ; Serotonin 5-HT2 receptor ; α1-Adrenoceptor ; Conditioned avoidance response ; Rats
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Using a conditioned avoidance procedure in rats, the present study examined the ability of 8-OH-DPAT, ritanserin, and prazosin to alter the effects of the dopamine antagonists, raclopride and haloperidol, on avoidance- and on escape responding. The 5-HT1A agonist 8-OH-DPAT (0.16 mg/kg) significantly enhanced the inhibitory effects of both raclopride and haloperidol on the conditioned avoidance response and produced a small enhancement of the effects of haloperidol on escape failures. The α1-adrenoceptor antagonist prazosin (0.63 mg/kg) significantly enhanced the effects of raclopride on the conditioned avoidance response, but enhanced the effects of only a single dose of haloperidol; prazosin did not alter the effects of either dopamine antagonist on escape failures. The 5-HT2 antagonist ritanserin (0.16 mg/kg) failed significantly to alter the effects of the dopamine antagonists examined here. These findings suggest that blockade of 5-HT2 receptors may not enhance the antipsychotic efficacy of D2-like antagonists. Further, they confirm previous findings with respect to interactions between 5-HT1A agonists and neuroleptics, and support the hypothesis that combined 5-HT1A agonist/D2-like antagonist properties may be of clinical importance.
    Materialart: Digitale Medien
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  • 7
    ISSN: 1432-2072
    Schlagwort(e): Key words Sensitization ; Reverse tolerance ; Tolerance ; Withdrawal ; Cocaine ; BTCP ; Locomotion ; Dopamine reuptake inhibitor ; Psychostimulant ; Dopamine transporter ; Addiction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Because the dopamine reuptake inhibitors cocaine and BTCP produce different behavioral effects after repeated administration, we studied whether they could alter each other’s effects by examining the effects of crossing over repeated treatment with cocaine and BTCP on cocaine-induced locomotion. Male C57BL/6 mice were treated repeatedly with cocaine or BTCP during a first phase (days 1–3) and 3 days later, treated repeatedly with the same or the other compound during a second phase (days 7–9), after which they were administered one of several doses of cocaine on the next day. Locomotor activity was assessed after every daily treatment. The results show that 1) cocaine induced sensitization to its locomotor effects, 2) cocaine-induced sensitization was not altered by subsequent repeated treatment with BTCP, 3) initial repeated treatment with BTCP induced apparent cross-tolerance to cocaine, and 4) the initial effects of repeated BTCP were not markedly altered by subsequent repeated treatment with cocaine. The results indicate that the initial effects produced by repeated cocaine or BTCP are enduring and relatively difficult to alter by crossing over repeated treatment with the other compound. Thus, sensitization to the locomotor effects of cocaine in mice appeared to be attenuated by prior repeated treatment with BTCP but not reversed when followed by repeated treatment with BTCP.
    Materialart: Digitale Medien
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 90 (1986), S. 475-481 
    ISSN: 1432-2072
    Schlagwort(e): Apomorphine ; Amphetamine ; Chlordiazepoxide ; Scopolamine ; Phencyclidine ; Pentobarbital ; Morphine ; Haloperidol ; Chlorpromazine ; Satiation ; Extinction ; Response repetition ; Response switching ; Pigeons
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Using a reinforcement schedule that arranges random sequences of reinforcements over two response keys, low and high probabilities of repetition of non-reinforced responses were generated in two groups of pigeons (n=3 per group) by varying the probability of reinforcement for responding on the key to which reinforcement was assigned. Unlike rats, the pigeons did not show a tendency to repeat just-reinforced responses, but showed a strong position bias, that was reduced by additional feeding and extinction, but not by any of the drug treatments. Apomorphine increased response repetition, irrespective of the control probability of repetition; d-amphetamine increased low probabilities of repetition, but decreased high probabilities. Chlordiazepoxide and scopolamine selectively decreased high probabilities of repetition; phencyclidine and pentobarbital selectively increased low probabilities of repetition. Morphine, haloperidol, chlorpromazine, additional feeding, and extinction did not affect repetition of non-reinforced responses. Extinction increased perseveration, whereas drug effects on perseveration were not observed. Drug-induced changes of patterning of responses as exemplified herein by drug-induced alterations of repetitiveness may be relevant to the interpretation of drug effects upon performance brought about by other behavioral processes such as discrimination.
    Materialart: Digitale Medien
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  • 9
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 72 (1981), S. 251-256 
    ISSN: 1432-2072
    Schlagwort(e): dl-Amphetamine ; Amylobarbitone ; Drug mixture ; PLG ; Fenfluramine ; Habituation ; Exploratory response ; General activity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A test situation was developed in which the effects of drugs on habituation of exploratory behavior (head-poke responses) could be assessed independently of their effects on general activity (locomotion and rearing). Habituation, spontaneous recovery from habituation and stimulus specificity of habituation were studied. An amphetamine-barbiturate mixture attenuated habituation of the head-poke response without influencing general activity. Pro-Leu-Gly-NH2 (PLG), an oxytocin fragment, increased locomotor activity and did not alter the course of habituation of the head-poke response. Since exploratory behavior and general activity can be pharmacologically dissociated in the test situation used, it is concluded that the test situation is suitable for studying the effects of drugs on habituation of exploratory behavior. The amphetamine-barbiturate mixture did not influence the stimulus specificity of habituation of the head-poke response. Fenfluramine however increased the effects of stimulus change on the head-poke response while not influencing habituation of this response. These results show that habituation and stimulus specificity of habituation of exploratory behavior can be pharmacologically dissociated.
    Materialart: Digitale Medien
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  • 10
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 131 (1997), S. 307-312 
    ISSN: 1432-2072
    Schlagwort(e): Key words β-Adrenergic receptors ; Tertatolol ; Cocaine ; Drug discrimination ; Dose versus dose discrimination ; ( ; )-Propranolol ; Nadolol ; ICI 118 ; 551 ; Betaxolol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Although many of the behavioral effects of cocaine are widely believed to be mediated by blockade of dopamine transporters, recent studies suggest that norepinephrine (NE) may play a modulatory role. In this study, selective and nonselective β-adrenergic receptor antagonists were administered alone or in combination with cocaine (2.5 mg/kg, IP) to rats trained to discriminate a low dose (2.5 mg/kg) from a high dose of cocaine (10 mg/kg) in a two-lever, FR10 drug discrimination procedure. The central β2/β1-adrenergic antagonists (–)-propranolol and tertatolol, and the β2-adrenergic antagonist, ICI 118,551, produced high-dose appropriate responding in a dose-related manner when administered (IP) in combination with the low training dose of cocaine. In contrast, neither the peripheral β2/β1-adrenergic antagonist, nadolol, nor the central β1-adrenergic antagonist, betaxolol enhanced the behavioral effects of the low dose of cocaine in a manner comparable with that produced by compounds with central β2-adrenergic antagonist properties. Also in contrast to findings obtained using β-adrenergic antagonists, neither the α1-adrenergic agonist cirazoline, nor the α2-adrenergic ligands (±)-efaroxan and UK-14304 enhanced the behavioral effects of the low dose of cocaine. Overall, these results suggest that central β2-adrenergic receptors may play a modulatory role in the discriminative stimulus effects of cocaine.
    Materialart: Digitale Medien
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