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  • 1
    Electronic Resource
    Electronic Resource
    A simple and rapid method for assessing similarities among directly observable behavioral effects of drugs: PCP-like effects of 2-amino-5-phosphonovalerate in rats (1987)
    Springer
    Psychopharmacology 91 (1987), S. 297-304 
    Details
    ISSN: 1432-2072
    Keywords: 2-Amino-5-phosphonovalerate (AP5) ; Excitatory amino acid antagonists ; Phencyclidine ; Ketamine ; Amphetamine ; Apomorphine ; Pentobarbital ; Chlordiazepoxide ; Directly observable behaviors ; Cumulative dosing ; Cluster analysis ; Classification ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Directly observable behavioral effects of the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (AP5) (10–1,000 mg/kg IP, 0.18–5.6 μmol/rat ICV) and of phencyclidine (PCP) (3.2–56 mg/kg IP, 0.032–3.2 mg/rat ICV), ketamine (10–100 mg/kg), amphetamine (1–18 mg/kg), apomorphine (0.1–5.6 mg/kg), chlordiazepoxide (1–100 mg/kg), and pentobarbital (3.2–56 mg/kg) were studied in rats. Pharmacologically specific results were obtained rapidly and reliably, using a cumulative dosing procedure. Cluster analysis grouped the drug treatments, on the basis of their similarities in producing different behavioral activities, into three main clusters; characteristically, stimulant drugs (amphetamine, apomorphine) produced sniffing and gnawing; PCP-like drugs (PCP, ketamine) produced locomotion, sniffing, swaying and falling; sedative drugs (pentobarbital, chlordiazepoxide) produced loss of righting. The behavioral effects of ICV administration of AP5 were more similar to the effects of PCP-like drugs than to the effects of either stimulant or sedative drugs, thus supporting the hypothesis that the behavioral effects of PCP-like drugs may result from reduced neurotransmission at excitatory synapses utilizing NMDA preferring receptors. The present procedure is simple, rapid and may provide a useful approach in the classification of behaviorally active drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00518181
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  • 2
    Electronic Resource
    Electronic Resource
    Can the DRL 72s schedule selectively reveal antidepressant drug activity? (1995)
    Springer
    Psychopharmacology 117 (1995), S. 154-161 
    Details
    ISSN: 1432-2072
    Keywords: Antidepressants ; DRL 72s schedule Water reinforcement ; Chlordiazepoxided-Amphetamine ; Haloperidol ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of three antidepressants, desipramine (2.5–20 mg/kg) tranylcypromine (0.63–2.5 mg/kg) mianserin (1.25–10 mg/kg) and three non-antidepressants, chlordiazepoxide (CDP; 1.25–10 mg/kg) haloperidol (0.02–0.16 mg/kg)d-amphetamine (0.31–1.25 mg/kg) were evaluated in rats responding for water reinforcement under a DRL 72s schedule. The antidepressants all produced dose-related decreases in overall response rates, but no significant changes in reinforcement frequency. In contrast, the anxiolytic CDP did increase the number of reinforcers obtained. Haloperidol decreased both reinforcers and responses whilstd-amphetamine stimulated responding, thereby decreasing reinforcement frequency. An analysis of the modes of inter-response times (IRTs) revealed no significant shifts in the peaks of the IRT distributions for most of the drugs tested. Amphetamine, however, (0.31 and 0.63 mg/kg) decreased the modal values in correspondence with the shift to the left of the peak of responding caused by this compound. These results are discussed in the context of the use of the DRL 72s procedure as a screening test for antidepressant drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245181
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  • 3
    Electronic Resource
    Electronic Resource
    Empirical evidence that the state dependence and drug discrimination paradigms can generate different outcomes (1995)
    Springer
    Psychopharmacology 120 (1995), S. 272-279 
    Details
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Cue ; State dependence ; State ; Ethanol ; Learning ; Memory
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The study compared the outcomes generated by the State Dependence and Drug Discrimination paradigms with ethanol in the rat. Food-deprived rats learned to complete a fixed-ratio 10 schedule of bar presses for food within 120 s while treated with 320- to 1250-mg/kg doses of ethanol. Subsequent tests of recall of this response with saline failed to generate any evidence that transfer was hampered following the drug-to-saline state change. In contrast, each of 14 rats learned to discriminate 1250 mg/kg ethanol from saline in a Drug Discrimination procedure that also required the animals to press one of two levers for food according to a fixed- ratio 10 schedule. The results offer the first empirical evidence to demonstrate directly that the State Dependence and Drug Discrimination paradigms can generate different outcomes in otherwise identical experimental conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02311174
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  • 4
    Electronic Resource
    Electronic Resource
    In vivo estimates of efficacy at 5-HT1A receptors: effects of EEDQ on the ability of agonists to produce lower-lip retraction in rats (2000)
    Springer
    Psychopharmacology 149 (2000), S. 377-387 
    Details
    ISSN: 1432-2072
    Keywords: Key words 5-HT1A agonist ; Intrinsic activity ; Efficacy ; Irreversible antagonism ; Lower-lip retraction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Maximal responses are often used as a measure of intrinsic activity or efficacy, but cannot be directly equated to efficacy. Using irreversible antagonists, estimates of efficacy can be obtained that may be less dependent on specific conditions. Objectives: To characterize the intrinsic activity of serotonin (5-HT)1A agonists by examining the effects of an irreversible antagonist on their ability to produce 5-HT1A receptor-mediated responses. Methods: The effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on the ability of 5-HT1A agonists to produce lower-lip retraction (LLR) in rats were studied. Results: In the absence of EEDQ, each 5-HT1A agonist produced full effects, the rank order of potency being: S 14506 〉 8-OH-DPAT 〉 buspirone 〉 ipsapirone. EEDQ decreased the number of 5-HT1A binding sites and shifted the dose–response curves (DRCs) of each agonist either to the right or, at higher EEDQ doses, to the right and downward. The manner in which these shifts occurred, however, differed among the compounds. For each agonist, all DRCs obtained after different doses of EEDQ were fitted to models proposed by Furchgott and Black and Leff, and the results indicated the following rank order of efficacy: ipsapirone 〈 buspirone ≈ 8-OH-DPAT 〈 S 14506. 5-HT1A agonist-induced LLR appears to be mediated by 5-HT1A receptors, because the 5-HT1A antagonist, WAY 100635, shifted the agonist DRCs to the right in a parallel and dose-related manner, with pA2 values ranging from 7.8 to 8.1. Moreover, pretreatment with WAY 100635 protected against the antagonist activity of EEDQ. Conclusions: The results suggest that the effects of EEDQ on the ability of 5-HT1A agonists to produce LLR in rats may be useful to obtain estimates of their apparent efficacy at 5-HT1A receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130000374
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  • 5
    Electronic Resource
    Electronic Resource
    External stimulus control in a “drug-discrimination” procedure: Drug effects and inter-animal variation (1984)
    Springer
    Psychopharmacology 82 (1984), S. 168-173 
    Details
    ISSN: 1432-2072
    Keywords: Stimulus control ; Drug discrimination ; Morphine ; Chlorpromazine ; Scopolamine ; Haloperidol ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats (N=12) were trained to discriminate between two stimulus conditions S1 and S2, consisting of combinations of visual and tactile stimuli [S1: box lighted (L) and wooden floor insert present (W); S2: box dark (D) and grid floor present (G)] in a two-lever discrimination procedure. S1 was continuously present during half of the sessions, and S2 was continuously present during the remaining sessions. Morphine (0.3–6 mg/kg) and haloperidol (0.04–0.08 mg/kg), but not chlorpromazine (1–4 mg/kg) and scopolamine (0.031–0.125 mg/kg), decreased the accuracy of discriminative responding during S1 sessions. None of the drugs significantly affected discrimination accuracy during S2 sessions. After drug testing was completed, reversed combinations of the visual and tactile stimuli were tested (i.e. L+G, and D+W). Inter-animal variation in the control by the component stimuli was observed. The results suggest that “intermediate results” (i.e. equal responding on drug and saline lever) in drug discrimination research, if observed at the highest dose of a drug at which animals still respond, may be interpreted in terms of a drug-induced disruption of discriminative responding. The results further suggest that inter-animal variation in the outcome of drug generalization tests may be partly related to inter-animal variation in the degree of stimulus control by different components of the training drug stimulus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427767
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  • 6
    Electronic Resource
    Electronic Resource
    Acute effects of naloxone and naltrexone, but lack of delayed effects, on exploratory behavior in the rat (1984)
    Springer
    Psychopharmacology 84 (1984), S. 383-387 
    Details
    ISSN: 1432-2072
    Keywords: Naloxone ; Naltrexone ; Exploration ; Locomotor activity ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Exploratory head-poke responses, locomotor activity, and rearing were studied in five groups of rats (n=8 per group) during two 30-min sessions. The opiate antagonists naloxone and naltrexone (0.5 and 2 mg/kg) were administered once, 30 min before the first session. Delayed drug effects were studied during the second session, 24 h after the first session. During the initial 10 min of the first session naloxone and naltrexone decreased the number of head-poke responses without reducing locomotor activity and rearing. Both drugs decreased the number of head-poke responses, locomotor activity, and rearing during the remainder of this session. Equivalent doses of naloxone and naltrexone produced similar effects. The duration of a head-poke response increased during the session. Drug effects on head-poke duration were not observed. Delayed drug effects on behavior during the second session were not obtained. The observation that both naloxone and naltrexone were effective in the present procedure suggests that the effects of naloxone and naltrexone reported here are a function of opiate antagonist properties of these drugs. The data suggest further that the extent to which opiate receptor blockade results in a specific reduction of exploratory behavior may be partly dependent upon the length of the test session.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00555217
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  • 7
    Electronic Resource
    Electronic Resource
    Phencyclidine (PCP)-like discriminative stimulus effects of metaphit and of 2-amino-5-phosphonovalerate in pigeons: generality across different training doses of PCP (1987)
    Springer
    Psychopharmacology 93 (1987), S. 437-442 
    Details
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Training dose ; Pharmacological specificity ; Threshold dose analysis ; Phencyclidine ; Excitatory amino acids ; Receptor acylator ; 2-Amino-5-phosphonovalerate (AP5) ; Metaphit ; Pentobarbital ; Chlordiazepoxide ; Pigeons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pigeons were trained to discriminate either a fixed dose of PCP (1 mg/kg; n=3) or a progressively decreasing dose (1-0.56–0.32 mg/kg; n=4) from saline. Lowering of the training dose shifted the dose-effect curve for PCP's discriminative stimulus effects about 5-fold to the left, in a parallel manner, but did not decrease the accuracy of the discrimination performance and did not significantly increase the extent to which pentobarbital and chlordiazepoxide produced PCP-appropriate responding. Dose-effect curves based on binary generalization data were evaluated statistically with new methods that may be more appropriate than those used previously. Metaphit, a proposed PCP-receptor acylator, and 2-amino-5-phosphonovalerate (AP5), an N-methyl-d-aspartate (NMDA) antagonist, produced complete PCP-appropriate responding in the high training dose group only at doses that suppressed the rate of responding and that produced ataxia. However, 4-fold lower doses of metaphit and AP5, which did not produce directly observable behavioral effects, were found to substitute completely for PCP in the low training dose group. These data support the notion that PCP, metaphit, and AP5 have a common discriminative effect in pigeons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00207232
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  • 8
    Electronic Resource
    Electronic Resource
    Repeated administration of cocaethylene induces context-dependent sensitization to its locomotor effects (1996)
    Springer
    Psychopharmacology 124 (1996), S. 300-305 
    Details
    ISSN: 1432-2072
    Keywords: Cocaine ; Dopamine reuptake blockers ; Reverse tolerance ; Convulsions ; Context-dependency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The cocaine analog, cocaethylene, has recently been identified as an active metabolite in humans consuming ethanol and cocaine. Since this compound exhibits affinity for the dopamine transporter that is more selective than that of cocaine, it is conceivable that its behavioral properties may be distinguishable from those of cocaine (cf. Elsworth et al. 1993). To investigate further the behavioral effects of cocaethylene, its ability to induce sensitization to locomotor activity in C57BL/6 mice was determined and compared with that of cocaine. In the first part of the study, mice were treated repeatedly with cocaethylene in the test environment and were then challenged with several different doses of the same drug. Repeated administration of 10, 20 or 40 mg/kg cocaethylene (IP) for 3 consecutive days produced leftward and upward shifts of the cocaethylene (2.5–56.6 mg/kg, IP) doseeffect curve on day 4. In the second part of the study, mice were treated with 20 mg/kg cocaethylene for 3 days, but were immediately placed back in their home cage following the injection: repeated administration of cocaethylene for 3 consecutive days did not significantly affect the dose-effect curve of cocaethylene (2.5–40 mg/kg, IP) on day 4. In the same paradigm, repeated administration of 20 mg/kg cocaine for 3 consecutive days produced a significant leftward shift of the cocaine (2.5–56.6 mg/kg, IP) dose-effect curve on day 4. These results confirm that cocaethylene shares a number of properties with cocaine, but also suggest that the drugs are not identical.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02247434
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  • 9
    Electronic Resource
    Electronic Resource
    Effects of d-amphetamine and morphine on delayed discrimination: Signal detection analysis and assessment of response repetition in the performance deficits (1984)
    Springer
    Psychopharmacology 83 (1984), S. 346-350 
    Details
    ISSN: 1432-2072
    Keywords: Visual discrimination ; Short-term memory ; Signal detection analysis ; Response repetition ; d-Amphetamine ; Morphine ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Signal detection analysis was used to examine the effects of d-amphetamine and of morphine on delayed visual discrimination (delay intervals: 0–4–8–16 s) in male rats. The probability of response repetition in the discrete trial two-choice discrimination procedure was used as an additional behavioral measure. d-Amphetamine (0.16–0.33 mg/kg) decreased SI (a measure of the animals' sensitivity to the discriminative stimuli) at delays between stimulus presentation and opportunity for responding of 4–16 s, and did not affect SI at the 0 s delay. Morphine (1–3 mg/kg) decreased SI at all delay conditions. d-Amphetamine, but not morphine, affected RI (a measure of the animals' bias towards responding on one lever or the other) and increased the probability of response repetition. The bias measure B″ was affected neither by d-amphetamine nor by morphine. It is concluded that d-amphetamine, but not morphine, produces a deterioration of delayed discrimination performance, probably as a result of drug-induced response perseveration. It is suggested that under the conditions of the present study, the selective deterioration of discrimination performance after d-amphetamine at delays which are longer than 0 s may not be primarily related to a drug-induced disruption of a short-term memory mechanism, but may be related to drug effects on response output.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00428543
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  • 10
    Electronic Resource
    Electronic Resource
    Effects of d-amphetamine and morphine on discrimination: signal detection analysis and assessment of response repetition in the performance deficits (1983)
    Springer
    Psychopharmacology 80 (1983), S. 125-128 
    Details
    ISSN: 1432-2072
    Keywords: Auditory Discrimination ; Signal detection ; Response Repetition ; d-Amphetamine ; Morphine ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Signal detection analysis was used to examine the effects of d-amphetamine and of morphine on auditory discrimination in female rats. The probability of response repetition in the discrete trial two-choice discrimination procedure was used as an additional behavioral measure. d-Amphetamine (0.4–3.2 mg/kg) and morphine (1.88–15.0 mg/kg) decreased the sensitivity measures (A′ and SI) but did not consistently affect the response bias measures (B″ and RI). The probability of response repetition was increased by d-amphetamine and was not affected by morphine. It is concluded that the response bias measure B″, derived from signal detection theory, and the empirical response bias measure RI, do not discriminate between the different ways in which d-amphetamine and morphine affect discriminative responding, under the conditions of this study.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427954
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