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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 92 (1987), S. 313-319 
    ISSN: 1432-2072
    Schlagwort(e): Pentylenetetrazol ; Morphine ; Fentanyl ; U 69 593 ; Mr 2034 ; Bremazocine ; Phencyclidine ; Drug discrimination ; Anxiety ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rats were trained to detect the stimulus properties of pentylenetetrazol (PTZ), 16 mg/kg, and prototypic drugs for mu, kappa and sigma opioid receptors were tested for their ability to block or substitute for PTZ. Only the sigma agonist, phencyclidine, showed any capacity for blocking the PTZ stimulus. Drugs with selective kappa or sigma actions did not substitute for PTZ. However, morphine, fentanyl and Mr 2034 did substitute for the PTZ stimulus. This substitution was found to be centrally mediated in that quaternary morphine did not produce a PTZ-like stimulus. In contrast to the substitution of these drugs for PTZ, in rats trained to detect the stimulus properties of fentanyl, no substitution of PTZ for the fentanyl stimulus occurred. In tests of the capacity of various drugs to block the PTZ-like stimulus of mu agonists, the stimulus produced by morphine or fentanyl was blocked by naloxone, diazepam and haloperidol, but not by scopolamine. These results demonstrate that drugs with mu agonist properties show a one-way substitution for the discriminative stimulus produced by PTZ. The observation that haloperidol blocked the PTZ-like stimulus of mu agonists suggests the possible involvement of dopaminergic mechanisms in the mediation of the effect.
    Materialart: Digitale Medien
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 93 (1987), S. 435-436 
    ISSN: 1432-2072
    Schlagwort(e): Drug discrimination ; Pentylenetetrazol ; Cocaine ; Learning
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rats were trained to discriminate “drug” from “no drug” in a two-lever, food-reinforced task. One group was trained with cocaine (10 mg/kg) and a second group was trained with pentylenetetrazol (20 mg/kg). A method designed to shorten the time required for the training phase of drug discrimination experiments was assessed in subgroups for each drug. In one subgroup, single training sessions were conducted daily. In the other subgroup, a second session (either drug or saline) was conducted on days for which the first condition was saline. The training conditions were presented in an irregular sequence, with the same condition occurring in no more than two consecutive sessions. Rats trained by the accelerated method learned the discrimination in fewer days, with no decrement in acquisition per session, suggesting that drug discrimination training can be accomplished more rapidly by reducing inter-session interval.
    Materialart: Digitale Medien
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 94 (1988), S. 183-187 
    ISSN: 1432-2072
    Schlagwort(e): Drug discrimination ; Pentylenetetrazol ; Operant behavior
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rats were trained to discriminate pentylenetetrazol (PTZ, 20 mg/kg) from saline in a two-lever operant task. Correct lever presses were reinforced with food under the control of a fixed ratio 10 schedule. In tests of the effect of PTZ dose on level selection, rats selected the PTZ lever in a dose-dependent manner, with peak latency at the approximate ED50 dose (10 mg/kg). Rats usually pressed only the selected lever, regardless of dose, indicating that lever selection was a quantal (or bimodal) function of stimulus intensity. Lever biases observed during training sessions did not predict the performance of individual rats in tests with the ED50 dose. In three independent trials with this intermediate dosage, the rats selecting the PTZ lever varied from trial to trial, suggesting that rats detecting this dose did not form a stable subgroup. The pattern of lever selections across these three trials was not significantly different from that predicted by a model in which all subjects shared the same probability for detecting the drug stimulus. These results demonstrate that lever selection in a two-lever drugdiscrimination task can be quantal in nature, and suggest that rats trained with PTZ, 20 mg/kg, are homogeneous in sensitivity to this stimulus.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 99 (1989), S. 422-422 
    ISSN: 1432-2072
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 96 (1988), S. 110-115 
    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
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  • 6
    ISSN: 1432-2072
    Schlagwort(e): Pentylenetetrazol ; Drug dependence ; Withdrawal ; Mecamylamine ; Discrimination ; Diazepam ; Nicotine ; Anxiety
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rats were trained on an FR10 schedule of food reinforcement to press one lever after pentylenetetrazol (PTZ), 20 mg/kg, IP, and an alternate lever after saline. After acute nicotine, 0.64 mg/kg, SC, 35% of the rats pressed the PTZ-lever. Diazepam, 5 mg/kg, IP, blocked the stimulus produced by PTZ, and mecamylamine, 5 mg/kg, IP, blocked the stimulus produced by nicotine. Training was then suspended and rats were treated with nicotine, at 8-h intervals, 0.64 mg/kg on the 1st day, and 1.25 mg/kg on subsequent days, for 21 days. To determine whether nicotine withdrawal substitutes for the stimulus produced by PTZ, rats were tested with saline at various times after chronic nicotine injections. Data from this part of the study were replicated in another group given nicotine for 15 days. Saline at 8 h after nicotine (five determinations each group) produced a small but stable degree of PTZ lever selection (35±4%). At 48 h after termination of nicotine treatment, the percentage of rats selecting the PTZ lever (50%) was greater than that in a control group tested after an equivalent period without training. The PTZ-like stimulus detected after chronic nicotine was not altered by mecamylamine, was additive with PTZ, and was blocked by diazepam. These data suggest that withdrawal from chronic nicotine produces a weak PTZ-like stimulus, which can be antagonized by an anxiolytic drug.
    Materialart: Digitale Medien
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  • 7
    ISSN: 1432-2072
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 116 (1994), S. 326-332 
    ISSN: 1432-2072
    Schlagwort(e): Cocaine ; Progressive-ratio schedule ; Rats ; Self-administration ; Tolerance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract This experiment used rats to test whether a regimen of chronic cocaine would produce tolerance to cocaine i.v. self-administration under a progressive ratio (PR) schedule of reinforcement. Under this PR schedule, an increasing number of responses was required to complete the ratio for each subsequent cocaine injection, and failure to complete the required ratio for the next injection within 1 h of the previous cocaine injection terminated the session. The number of injections taken in the session was termed the breaking point and used as the dependent variable. Rats were trained under this schedule until breaking point values were stable, after which cocaine dose-effect data were obtained: the breaking point increased as the dose of cocaine increased. Subsequently, rats were assigned to one of two groups for 7 days of chronic treatment: one group was infused with cocaine (18 mg/kg, given over 20 min once every 8 h) and the other group received 0.9% saline. Following termination of chronic treatment, cocaine dose-effect data were redetermined in both groups. Chronic cocaine treatment significantly decreased breaking point values across the entire dose-effect curve, although the effect was observed in only four of seven subjects. In contrast, chronic saline treatment produced no significant effect on the breaking point measures. Following a further 5 days of recovery from chronic treatment, cocaine dose-effect data were redetermined in both groups; these curves were essentially identical to those obtained before chronic treatments. These data support the hypothesis that tolerance occurs to the reinforcing effects of cocaine, as measured by a decrease in the breaking point, at least for a subset of animals.
    Materialart: Digitale Medien
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  • 9
    ISSN: 1432-2072
    Schlagwort(e): Genetic basis of substance abuse ; Inbred strains ; Cocaine ; Self-administration ; Progressive-ratio ; Restriction fragment length polymorphisms ; Rats ; D1 receptor ; D2 receptor ; Dopamine ; SCH 23390 ; Eticlopride
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract This study investigated the influence of genetics on extent of cocaine taking in rats that were self-administering cocaine under a progressive-ratio schedule. Fischer 344, ACI and Brown Norway rats were subjects because previous genetic studies on dopamine receptor loci have indicated that these are genetically divergent strains. All subjects were assessed for acquisition and stability of cocaine self-administration under a progressive-ratio schedule. Subsequently, a dose-effect curve for cocaine self-administration was determined for each strain. Fischer 344 rats maintained a higher average breaking point than did the ACI or Brown Norway strains. In addition, dopamine receptor antagonists differentially reduced the ability of cocaine to serve as a reinforcer across the three strains. The D1-selective dopamine receptor antagonist, SCH 23390, and the D2/D3-selective dopamine receptor antagonist, eticlopride, were significantly more effective in reducing the self-administration of cocaine in Brown Norway rats than for the other two strains. The results of this study demonstrate that genetic differences may play an important role in determining responding under progressive-ratio schedules for cocaine, possibly due to differences in the reinforcing efficacy of cocaine.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 10
    ISSN: 1432-2072
    Schlagwort(e): Key words Genetic basis of substance abuse ; Inbred strains ; Cocaine ; Self-administration ; Progressive-ratio ; Restriction fragment length polymorphisms ; Rats ; D1 receptor ; D2 receptor ; Dopamine ; SCH 23390 ; Eticlopride
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  This study investigated the influence of genetics on extent of cocaine taking in rats that were self-administering cocaine under a progressive-ratio schedule. Fischer 344, ACI and Brown Norway rats were subjects because previous genetic studies on dopamine receptor loci have indicated that these are genetically divergent strains. All subjects were assessed for acquisition and stability of cocaine self-administration under a progressive-ratio schedule. Subsequently, a dose-effect curve for cocaine self-administration was determined for each strain. Fischer 344 rats maintained a higher average breaking point than did the ACI or Brown Norway strains. In addition, dopamine receptor antagonists differentially reduced the ability of cocaine to serve as a reinforcer across the three strains. The D1-selective dopamine receptor antagonist, SCH 23390, and the D2/D3-selective dopamine receptor antagonist, eticlopride, were significantly more effective in reducing the self-administration of cocaine in Brown Norway rats than for the other two strains. The results of this study demonstrate that genetic differences may play an important role in determining responding under progressive-ratio schedules for cocaine, possibly due to differences in the reinforcing efficacy of cocaine.
    Materialart: Digitale Medien
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