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  • 1
    Electronic Resource
    Electronic Resource
    Opioid modulation of the discriminative stimulus produced by pentylenetetrazol (1987)
    Springer
    Psychopharmacology 92 (1987), S. 313-319 
    Details
    ISSN: 1432-2072
    Keywords: Pentylenetetrazol ; Morphine ; Fentanyl ; U 69 593 ; Mr 2034 ; Bremazocine ; Phencyclidine ; Drug discrimination ; Anxiety ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00210836
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  • 2
    Electronic Resource
    Electronic Resource
    Quantal detection and homogeneous sensitivity in a pentylenetetrazol discrimination (1988)
    Springer
    Psychopharmacology 94 (1988), S. 183-187 
    Details
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Pentylenetetrazol ; Operant behavior
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00176842
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  • 3
    Electronic Resource
    Electronic Resource
    Reply to J.R. Hughes, S.T. Higgins, and W.K. Bichel: Behavioral “properties” of drugs (1989)
    Springer
    Psychopharmacology 99 (1989), S. 422-422 
    Details
    ISSN: 1432-2072
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00445570
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  • 4
    Electronic Resource
    Electronic Resource
    Withdrawal from chronic nicotine substitutes partially for the interoceptive stimulus produced by pentylenetetrazol (PTZ) (1986)
    Springer
    Psychopharmacology 90 (1986), S. 85-89 
    Details
    ISSN: 1432-2072
    Keywords: Pentylenetetrazol ; Drug dependence ; Withdrawal ; Mecamylamine ; Discrimination ; Diazepam ; Nicotine ; Anxiety
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00172876
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  • 5
    Electronic Resource
    Electronic Resource
    A method to shorten the training phase of drug discrimination (1987)
    Springer
    Psychopharmacology 93 (1987), S. 435-436 
    Details
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Pentylenetetrazol ; Cocaine ; Learning
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00207231
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  • 6
    Electronic Resource
    Electronic Resource
    Variations in cocaine self-administration by inbred rat strains under a progressive-ratio schedule (1996)
    Springer
    Psychopharmacology 127 (1996), S. 204-212 
    Details
    ISSN: 1432-2072
    Keywords: 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
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050078
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  • 7
    Electronic Resource
    Electronic Resource
    Discriminative stimulus effects of midazolam and abecarnil in rats treated chronically with diazepam or abecarnil (1995)
    Springer
    Psychopharmacology 121 (1995), S. 339-346 
    Details
    ISSN: 1432-2072
    Keywords: Abecarnil ; Diazepam ; Midazolam ; Benzodiazepine ; Tolerance ; Cross-tolerance ; Discriminative stimulus ; Partial agonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Abecarnil (ABC) is a beta-carboline that acts as an agonist at benzodiazepine (BZD) receptors. It possesses anxiolytic and anticonvulsant properties, but produces little sedation and is without muscle relaxant effects. To explain this unusual profile of activity, two hypotheses have been advanced: either 1) ABC acts as a partial agonist or 2) ABC acts as a full agonist, but only at a sub-population of BZD receptors. The present experiment used cross-tolerance profiles between BZDs and ABC to differentiate these hypotheses based upon predictions of receptor theory: tolerance produced to a full agonist should confer even greater cross-tolerance to a partial agonist. Rats were trained in a three-choice drug discrimination procedure to detect the benzodiazepine, midazolam (MDZ, 1.0 mg/kg) from pentylenetetrazole (PTZ, 20 mg/kg) from saline. Tested acutely, MDZ and ABC substituted for MDZ with similar potencies. Following chronic treatment with the BZD-agonist diazepam (DZP; 20 mg/kg per 8 h for 7 days), both the MDZ and ABC dose-effect curves were significantly shifted to the right, and both drugs showed a comparable three-fold decrease in potency. The chronic administration of ABC (4.0 mg/kg per 8 h for 7 days) produced a different spectrum of results. No significant shift occurred in the MDZ dose-effect curve, but there was a significant seven-fold shift to the right of the ABC dose-effect curve. Throughout all tests, PTZ-lever responding rarely occurred and did not account for more than 20% of lever selections for any individual test. These data support the hypothesis that ABC acts as a full agonist at a sub-population of BZD receptors, which mediate its substitution for MDZ.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246073
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  • 8
    Electronic Resource
    Electronic Resource
    Animal models of drug withdrawal symptoms (1990)
    Springer
    Psychopharmacology 101 (1990), S. 292-309 
    Details
    ISSN: 1432-2072
    Keywords: Drugs of abuse ; Drug withdrawal ; Drug discrimination ; Discriminative stimulus ; Withdrawal signs ; Withdrawal symptoms ; Benzodiazepines ; Diazepam ; Ethanol ; Cocaine ; Anxiety ; Drug dependence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There have been few attempts to model subjective symptoms of drug withdrawal using animals as subjects. Two approaches for developing such models are reviewed. First, using drug discrimination methodology, it may be possible to train animals to detect the effects of withdrawal. This method has two difficulties: 1) the only discriminations trained to date involve precipitated withdrawal, and 2) the stimulus controlling behavior is difficult to specify. Second, withdrawal from many drugs of abuse produces the symptom of anxiety, and it seems likely that animal models of anxiety could be useful for studying drug withdrawal. This hypothesis has been explored most fully using subjects trained to detect the discriminative stimulus properties of the putative anxiogenic drug pentylenetetrazole (PTZ). Withdrawal from benzodiazepines or ethanol substitutes fully for PTZ, and withdrawal from cocaine, morphine, and nicotine substitutes partially for PTZ. Emerging data suggest that other animal models of anxiety may also be useful for detecting drug withdrawal. The final portion of this review examines a behavioral test that is very sensitive for detecting physical signs of withdrawal in animals. In subjects maintained on an operant baseline using food as a reinforcer, withdrawal from a drug of dependence frequently is associated with disruption of that operant behavior. For example, tetrahydrocannabinol and cocaine, drugs that are not traditionally seen as having significant withdrawal signs, produce disruption of operant responding when high-dose administration is terminated, and their readministration reverses this behavioral disruption. Based on the observation that withdrawal is associated with anxiogenic stimuli, we suggest a method to determine if disruption of operant behavior may be related to these stimuli.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244046
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  • 9
    Electronic Resource
    Electronic Resource
    Tolerance to the reinforcing effects of cocaine in a progressive ratio paradigm (1994)
    Springer
    Psychopharmacology 116 (1994), S. 326-332 
    Details
    ISSN: 1432-2072
    Keywords: Cocaine ; Progressive-ratio schedule ; Rats ; Self-administration ; Tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245336
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  • 10
    Electronic Resource
    Electronic Resource
    Commentary on “Drug discrimination is a continuous rather than a quantal process following training on a VI-TO schedule of reinforcement” by Barrett et al. (1994)
    Springer
    Psychopharmacology 113 (1994), S. 300-301 
    Details
    ISSN: 1432-2072
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245199
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