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J-a. W. White - One of the best experts on this subject based on the ideXlab platform.
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AND and AND-OR Drug Mixture discriminations in rats: generalization to single Drugs and Drug Mixtures.
Psychopharmacology, 1999Co-Authors: E. A. Mariathasan, Ian P. Stolerman, J-a. W. WhiteAbstract:Rationale: Studies of the discriminative stimulus effects of Drug Mixtures provide an approach to polyDrug abuse and studies on single Drugs with multiple effects. Objective: This study was designed to investigate whether the use of the AND-OR procedure increases the specificity of Drug Mixture discriminations. Methods: Rats were trained to discriminate a Mixture of amphetamine (0.4 mg/kg) plus pentobarbitone (10 mg/kg) from saline (AND-discrimination, n = 8) or to discriminate the same Mixture from its component Drugs alone (AND–OR discrimination, n = 9). The studies used two-lever operant procedures with a tandem variable interval 1-min fixed ratio 10 schedule of food reinforcement. Results: Under AND-discrimination conditions, there was partial generalization to nicotine and midazolam when each Drug was administered singly, and there was no generalization to cocaine, caffeine or ethanol. With the AND-OR discrimination, there was no generalization to any of the preceding Drugs administered singly. In “single substitution” tests, nicotine or midazolam was co-administered with the training doses of pentobarbitone and amphetamine, respectively; there was full generalization in the AND-discrimination and partial generalization under AND-OR conditions. Cocaine co-administered with pentobarbitone generalized fully under both procedures, but the dose of cocaine needed was much larger in the AND-OR than in the AND-discrimination. In “dual substitution” tests, Mixtures of two novel substances were tested. Mixtures of either nicotine plus midazolam or caffeine plus ethanol produced very marked generalization under AND-discrimination conditions, but were without significant effect in the AND-OR procedure. Throughout the studies, in every instance where comparisons were made, generalization was greater or occurred at lower doses under AND- than under the AND-OR discrimination. Conclusions: The study yielded extensive evidence supporting the hypothesis that the AND-OR discrimination procedure increases the specificity of discriminations based on Drug Mixtures.
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Influencing the specificity of Drug Mixture discriminations by varying the training procedure.
Behavioural Pharmacology, 1999Co-Authors: Ian P. Stolerman, E. A. Mariathasan, J-a. W. WhiteAbstract:Studies of the discriminative stimulus effects of Drug Mixtures provide an approach to polyDrug abuse and to studies on single Drugs with multiple effects. The experiments described here investigated whether the use of the AND-OR procedure increases the specificity of Drug Mixture discriminations. Rats were trained to discriminate a Mixture of nicotine (0.4 mg/ kg) plus midazolam (0.2 mg/kg) from saline (AND-discrimination, n = 10) or to discriminate the same Mixture from its component Drugs alone (AND-OR discrimination, n = 10). The studies used two-lever operant procedures with a tandem variable interval 1 min fixed ratio 10 (FR 10) schedule of food reinforcement. Under AND-discrimination conditions, there was partial generalization to amphetamine and pentobarbitone when each Drug was administered singly. With the AND-OR-discrimination, there was no generalization to amphetamine and partial generalization to pentobarbitone. In 'single substitution' tests, pentobarbitone or amphetamine was co-administered with the training doses of nicotine and midazolam, respectively; there was full generalization in the AND-discrimination and no generalization under AND-OR conditions. In 'dual substitution' tests, Mixtures of amphetamine plus pentobarbitone produced full generalization under AND-discrimination conditions, and partial generalization in the AND-OR procedure. Wherever comparisons were made, generalization was less under AND-OR- than under the AND-discrimination procedure, confirming that the AND-OR procedure can increase the specificity of discriminations based on Drug Mixtures. The similarity with findings reported previously for training with Mixtures of amphetamine plus pentobarbitone suggests that this may reflect a general principle rather than a phenomenon restricted to particular training Drugs.
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Influence of training paradigm on specificity of Drug Mixture discriminations.
Pharmacology biochemistry and behavior, 1999Co-Authors: E. A. Mariathasan, Ian P. Stolerman, J-a. W. WhiteAbstract:Generalization to different Drugs and Drug Mixtures has been examined in rats trained to discriminate a Mixture of amphetamine (0.4 mg/kg) plus pentobarbitone (10 mg/kg) from saline (AND discrimination, n = 8) or to discriminate the same Mixture from its component Drugs alone (AND-OR discrimination, n = 9). The studies used two-lever operant procedures with a tandem variable interval 1-min fixed-ratio 10 schedule of food reinforcement. There was partial generalization to nicotine and midazolam and no generalization to cocaine, caffeine, or ethanol under AND-discrimination conditions and no generalization to any of these Drugs in the AND-OR discrimination. Nicotine or midazolam coadministered with the training doses of pentobarbitone and amphetamine, respectively, produced full generalization in the AND discrimination and partial generalization under AND-OR conditions. Cocaine coadministered with pentobarbitone generalized fully under both procedures, but at larger doses in the AND-OR than in the AND discrimination. Mixtures of either nicotine plus midazolam or caffeine plus ethanol produced very marked generalization under AND-discrimination conditions, but were without significant effect in the AND-OR procedure. The results consistently supported the hypothesis that the AND-OR discrimination procedure increases the specificity of discriminations based on Drug Mixtures.
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Antagonism of AND and AND-OR Drug Mixture discriminations in rats
Drug and alcohol dependence, 1997Co-Authors: E. A. Mariathasan, Ian P. Stolerman, J-a. W. WhiteAbstract:Abstract It has been suggested that use of the AND-OR training method may be associated with an enhancement of the pharmacological specificity of discriminations based on Mixture of Drugs. Rats were trained to discriminate a Mixture of nicotine (0.4 mg/kg s.c.) plus midazolam (0.2 mg/kg s.c.) from saline (AND-discrimination, n = 8) or to discriminate the Mixture from either Drug alone (AND-OR discrimination, n = 6). The studies used two-lever operant procedures with food reinforcers presented on a tandem schedule. After discriminations were acquired to 80% accuracy, the nicotine antagonist mecamylamine (0.03–1.0 mg/kg s.c.) and the benzodiazepine antagonist flumazenil (0.32–10 mg/kg i.p.) were tested on the response to the Mixture of nicotine plus midazolam. The antagonist effects of either mecamylamine or flumazenil given alone were more marked in rats trained under the AND-OR procedure than in rats trained on the AND-discrimination. Similarly, the antagonist effects of Mixtures of mecamylamine plus flumazenil were much more potent under the AND-OR than under the AND-discrimination procedure. The AND-OR method reduced the dose of the antagonist Mixture needed to produce complete block by a factor of about 10, as compared with the AND-discrimination. These striking differences in sensitivity to antagonists support the view that AND-OR or related procedures may enhance the pharmacological specificity of complex Drug discriminations.
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Training dose as a decisive factor for discrimination of a Drug Mixture in rats.
Behavioural pharmacology, 1996Co-Authors: E. A. Mariathasan, J-a. W. White, Ian P. StolermanAbstract:The impact of training dose on the characteristics of a discrimination maintained by a Mixture of two dissimilar Drugs has been investigated in order to refine this approach to the study of Drug interactions. Three groups of rats (n = 10) were trained to discriminate Mixtures of (+)-amphetamine (0.2-0.8mg/kg) plus pentobarbitone (5-20mg/kg) from saline, in a two-lever operant procedure with food reinforcement, with the ratio of the doses held constant (amphetamine: pentobarbitone, 1:25). Discriminations were acquired to an accuracy of 90-97%. There was full generalisation to amphetamine alone, but only in rats trained with Mixtures of the smaller doses of the single Drugs. There was partial generalisation when either apomorphine (50%) or nicotine (63%) was administered alone, and the magnitude of these responses was inversely related to the dose of Mixture used for training. Doses of pentobarbitone half of those used for training produced little discriminative response when administered alone to rats trained with the two smallest doses of the Mixture; the same doses of pentobarbitone increased responses to amphetamine or apomorphine in a more than additive manner. Strikingly, some doses of apomorphine and pentobarbitone that did not generalise when administered separately, produced full generalisation when administered together, but only in rats trained with the smaller doses of the Mixture. In contrast, pentobarbitone did not enhance generalisation to nicotine in any group. It was concluded that, on the one hand, patterns of generalisation to single Drugs followed an orderly pattern resembling those for discriminations established with single Drugs. On the other hand, there was a complex pattern of generalization from one Mixture to another; thus, altering the doses of Drugs used for training markedly influenced discriminations of an abused Drug Mixture, but no simple rules to predict the influence of training dose have been ascertained.
Ian P. Stolerman - One of the best experts on this subject based on the ideXlab platform.
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AND and AND-OR Drug Mixture discriminations in rats: generalization to single Drugs and Drug Mixtures.
Psychopharmacology, 1999Co-Authors: E. A. Mariathasan, Ian P. Stolerman, J-a. W. WhiteAbstract:Rationale: Studies of the discriminative stimulus effects of Drug Mixtures provide an approach to polyDrug abuse and studies on single Drugs with multiple effects. Objective: This study was designed to investigate whether the use of the AND-OR procedure increases the specificity of Drug Mixture discriminations. Methods: Rats were trained to discriminate a Mixture of amphetamine (0.4 mg/kg) plus pentobarbitone (10 mg/kg) from saline (AND-discrimination, n = 8) or to discriminate the same Mixture from its component Drugs alone (AND–OR discrimination, n = 9). The studies used two-lever operant procedures with a tandem variable interval 1-min fixed ratio 10 schedule of food reinforcement. Results: Under AND-discrimination conditions, there was partial generalization to nicotine and midazolam when each Drug was administered singly, and there was no generalization to cocaine, caffeine or ethanol. With the AND-OR discrimination, there was no generalization to any of the preceding Drugs administered singly. In “single substitution” tests, nicotine or midazolam was co-administered with the training doses of pentobarbitone and amphetamine, respectively; there was full generalization in the AND-discrimination and partial generalization under AND-OR conditions. Cocaine co-administered with pentobarbitone generalized fully under both procedures, but the dose of cocaine needed was much larger in the AND-OR than in the AND-discrimination. In “dual substitution” tests, Mixtures of two novel substances were tested. Mixtures of either nicotine plus midazolam or caffeine plus ethanol produced very marked generalization under AND-discrimination conditions, but were without significant effect in the AND-OR procedure. Throughout the studies, in every instance where comparisons were made, generalization was greater or occurred at lower doses under AND- than under the AND-OR discrimination. Conclusions: The study yielded extensive evidence supporting the hypothesis that the AND-OR discrimination procedure increases the specificity of discriminations based on Drug Mixtures.
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Influencing the specificity of Drug Mixture discriminations by varying the training procedure.
Behavioural Pharmacology, 1999Co-Authors: Ian P. Stolerman, E. A. Mariathasan, J-a. W. WhiteAbstract:Studies of the discriminative stimulus effects of Drug Mixtures provide an approach to polyDrug abuse and to studies on single Drugs with multiple effects. The experiments described here investigated whether the use of the AND-OR procedure increases the specificity of Drug Mixture discriminations. Rats were trained to discriminate a Mixture of nicotine (0.4 mg/ kg) plus midazolam (0.2 mg/kg) from saline (AND-discrimination, n = 10) or to discriminate the same Mixture from its component Drugs alone (AND-OR discrimination, n = 10). The studies used two-lever operant procedures with a tandem variable interval 1 min fixed ratio 10 (FR 10) schedule of food reinforcement. Under AND-discrimination conditions, there was partial generalization to amphetamine and pentobarbitone when each Drug was administered singly. With the AND-OR-discrimination, there was no generalization to amphetamine and partial generalization to pentobarbitone. In 'single substitution' tests, pentobarbitone or amphetamine was co-administered with the training doses of nicotine and midazolam, respectively; there was full generalization in the AND-discrimination and no generalization under AND-OR conditions. In 'dual substitution' tests, Mixtures of amphetamine plus pentobarbitone produced full generalization under AND-discrimination conditions, and partial generalization in the AND-OR procedure. Wherever comparisons were made, generalization was less under AND-OR- than under the AND-discrimination procedure, confirming that the AND-OR procedure can increase the specificity of discriminations based on Drug Mixtures. The similarity with findings reported previously for training with Mixtures of amphetamine plus pentobarbitone suggests that this may reflect a general principle rather than a phenomenon restricted to particular training Drugs.
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Influence of training paradigm on specificity of Drug Mixture discriminations.
Pharmacology biochemistry and behavior, 1999Co-Authors: E. A. Mariathasan, Ian P. Stolerman, J-a. W. WhiteAbstract:Generalization to different Drugs and Drug Mixtures has been examined in rats trained to discriminate a Mixture of amphetamine (0.4 mg/kg) plus pentobarbitone (10 mg/kg) from saline (AND discrimination, n = 8) or to discriminate the same Mixture from its component Drugs alone (AND-OR discrimination, n = 9). The studies used two-lever operant procedures with a tandem variable interval 1-min fixed-ratio 10 schedule of food reinforcement. There was partial generalization to nicotine and midazolam and no generalization to cocaine, caffeine, or ethanol under AND-discrimination conditions and no generalization to any of these Drugs in the AND-OR discrimination. Nicotine or midazolam coadministered with the training doses of pentobarbitone and amphetamine, respectively, produced full generalization in the AND discrimination and partial generalization under AND-OR conditions. Cocaine coadministered with pentobarbitone generalized fully under both procedures, but at larger doses in the AND-OR than in the AND discrimination. Mixtures of either nicotine plus midazolam or caffeine plus ethanol produced very marked generalization under AND-discrimination conditions, but were without significant effect in the AND-OR procedure. The results consistently supported the hypothesis that the AND-OR discrimination procedure increases the specificity of discriminations based on Drug Mixtures.
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Antagonism of AND and AND-OR Drug Mixture discriminations in rats
Drug and alcohol dependence, 1997Co-Authors: E. A. Mariathasan, Ian P. Stolerman, J-a. W. WhiteAbstract:Abstract It has been suggested that use of the AND-OR training method may be associated with an enhancement of the pharmacological specificity of discriminations based on Mixture of Drugs. Rats were trained to discriminate a Mixture of nicotine (0.4 mg/kg s.c.) plus midazolam (0.2 mg/kg s.c.) from saline (AND-discrimination, n = 8) or to discriminate the Mixture from either Drug alone (AND-OR discrimination, n = 6). The studies used two-lever operant procedures with food reinforcers presented on a tandem schedule. After discriminations were acquired to 80% accuracy, the nicotine antagonist mecamylamine (0.03–1.0 mg/kg s.c.) and the benzodiazepine antagonist flumazenil (0.32–10 mg/kg i.p.) were tested on the response to the Mixture of nicotine plus midazolam. The antagonist effects of either mecamylamine or flumazenil given alone were more marked in rats trained under the AND-OR procedure than in rats trained on the AND-discrimination. Similarly, the antagonist effects of Mixtures of mecamylamine plus flumazenil were much more potent under the AND-OR than under the AND-discrimination procedure. The AND-OR method reduced the dose of the antagonist Mixture needed to produce complete block by a factor of about 10, as compared with the AND-discrimination. These striking differences in sensitivity to antagonists support the view that AND-OR or related procedures may enhance the pharmacological specificity of complex Drug discriminations.
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Training dose as a decisive factor for discrimination of a Drug Mixture in rats.
Behavioural pharmacology, 1996Co-Authors: E. A. Mariathasan, J-a. W. White, Ian P. StolermanAbstract:The impact of training dose on the characteristics of a discrimination maintained by a Mixture of two dissimilar Drugs has been investigated in order to refine this approach to the study of Drug interactions. Three groups of rats (n = 10) were trained to discriminate Mixtures of (+)-amphetamine (0.2-0.8mg/kg) plus pentobarbitone (5-20mg/kg) from saline, in a two-lever operant procedure with food reinforcement, with the ratio of the doses held constant (amphetamine: pentobarbitone, 1:25). Discriminations were acquired to an accuracy of 90-97%. There was full generalisation to amphetamine alone, but only in rats trained with Mixtures of the smaller doses of the single Drugs. There was partial generalisation when either apomorphine (50%) or nicotine (63%) was administered alone, and the magnitude of these responses was inversely related to the dose of Mixture used for training. Doses of pentobarbitone half of those used for training produced little discriminative response when administered alone to rats trained with the two smallest doses of the Mixture; the same doses of pentobarbitone increased responses to amphetamine or apomorphine in a more than additive manner. Strikingly, some doses of apomorphine and pentobarbitone that did not generalise when administered separately, produced full generalisation when administered together, but only in rats trained with the smaller doses of the Mixture. In contrast, pentobarbitone did not enhance generalisation to nicotine in any group. It was concluded that, on the one hand, patterns of generalisation to single Drugs followed an orderly pattern resembling those for discriminations established with single Drugs. On the other hand, there was a complex pattern of generalization from one Mixture to another; thus, altering the doses of Drugs used for training markedly influenced discriminations of an abused Drug Mixture, but no simple rules to predict the influence of training dose have been ascertained.
E. A. Mariathasan - One of the best experts on this subject based on the ideXlab platform.
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AND and AND-OR Drug Mixture discriminations in rats: generalization to single Drugs and Drug Mixtures.
Psychopharmacology, 1999Co-Authors: E. A. Mariathasan, Ian P. Stolerman, J-a. W. WhiteAbstract:Rationale: Studies of the discriminative stimulus effects of Drug Mixtures provide an approach to polyDrug abuse and studies on single Drugs with multiple effects. Objective: This study was designed to investigate whether the use of the AND-OR procedure increases the specificity of Drug Mixture discriminations. Methods: Rats were trained to discriminate a Mixture of amphetamine (0.4 mg/kg) plus pentobarbitone (10 mg/kg) from saline (AND-discrimination, n = 8) or to discriminate the same Mixture from its component Drugs alone (AND–OR discrimination, n = 9). The studies used two-lever operant procedures with a tandem variable interval 1-min fixed ratio 10 schedule of food reinforcement. Results: Under AND-discrimination conditions, there was partial generalization to nicotine and midazolam when each Drug was administered singly, and there was no generalization to cocaine, caffeine or ethanol. With the AND-OR discrimination, there was no generalization to any of the preceding Drugs administered singly. In “single substitution” tests, nicotine or midazolam was co-administered with the training doses of pentobarbitone and amphetamine, respectively; there was full generalization in the AND-discrimination and partial generalization under AND-OR conditions. Cocaine co-administered with pentobarbitone generalized fully under both procedures, but the dose of cocaine needed was much larger in the AND-OR than in the AND-discrimination. In “dual substitution” tests, Mixtures of two novel substances were tested. Mixtures of either nicotine plus midazolam or caffeine plus ethanol produced very marked generalization under AND-discrimination conditions, but were without significant effect in the AND-OR procedure. Throughout the studies, in every instance where comparisons were made, generalization was greater or occurred at lower doses under AND- than under the AND-OR discrimination. Conclusions: The study yielded extensive evidence supporting the hypothesis that the AND-OR discrimination procedure increases the specificity of discriminations based on Drug Mixtures.
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Influencing the specificity of Drug Mixture discriminations by varying the training procedure.
Behavioural Pharmacology, 1999Co-Authors: Ian P. Stolerman, E. A. Mariathasan, J-a. W. WhiteAbstract:Studies of the discriminative stimulus effects of Drug Mixtures provide an approach to polyDrug abuse and to studies on single Drugs with multiple effects. The experiments described here investigated whether the use of the AND-OR procedure increases the specificity of Drug Mixture discriminations. Rats were trained to discriminate a Mixture of nicotine (0.4 mg/ kg) plus midazolam (0.2 mg/kg) from saline (AND-discrimination, n = 10) or to discriminate the same Mixture from its component Drugs alone (AND-OR discrimination, n = 10). The studies used two-lever operant procedures with a tandem variable interval 1 min fixed ratio 10 (FR 10) schedule of food reinforcement. Under AND-discrimination conditions, there was partial generalization to amphetamine and pentobarbitone when each Drug was administered singly. With the AND-OR-discrimination, there was no generalization to amphetamine and partial generalization to pentobarbitone. In 'single substitution' tests, pentobarbitone or amphetamine was co-administered with the training doses of nicotine and midazolam, respectively; there was full generalization in the AND-discrimination and no generalization under AND-OR conditions. In 'dual substitution' tests, Mixtures of amphetamine plus pentobarbitone produced full generalization under AND-discrimination conditions, and partial generalization in the AND-OR procedure. Wherever comparisons were made, generalization was less under AND-OR- than under the AND-discrimination procedure, confirming that the AND-OR procedure can increase the specificity of discriminations based on Drug Mixtures. The similarity with findings reported previously for training with Mixtures of amphetamine plus pentobarbitone suggests that this may reflect a general principle rather than a phenomenon restricted to particular training Drugs.
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Influence of training paradigm on specificity of Drug Mixture discriminations.
Pharmacology biochemistry and behavior, 1999Co-Authors: E. A. Mariathasan, Ian P. Stolerman, J-a. W. WhiteAbstract:Generalization to different Drugs and Drug Mixtures has been examined in rats trained to discriminate a Mixture of amphetamine (0.4 mg/kg) plus pentobarbitone (10 mg/kg) from saline (AND discrimination, n = 8) or to discriminate the same Mixture from its component Drugs alone (AND-OR discrimination, n = 9). The studies used two-lever operant procedures with a tandem variable interval 1-min fixed-ratio 10 schedule of food reinforcement. There was partial generalization to nicotine and midazolam and no generalization to cocaine, caffeine, or ethanol under AND-discrimination conditions and no generalization to any of these Drugs in the AND-OR discrimination. Nicotine or midazolam coadministered with the training doses of pentobarbitone and amphetamine, respectively, produced full generalization in the AND discrimination and partial generalization under AND-OR conditions. Cocaine coadministered with pentobarbitone generalized fully under both procedures, but at larger doses in the AND-OR than in the AND discrimination. Mixtures of either nicotine plus midazolam or caffeine plus ethanol produced very marked generalization under AND-discrimination conditions, but were without significant effect in the AND-OR procedure. The results consistently supported the hypothesis that the AND-OR discrimination procedure increases the specificity of discriminations based on Drug Mixtures.
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Antagonism of AND and AND-OR Drug Mixture discriminations in rats
Drug and alcohol dependence, 1997Co-Authors: E. A. Mariathasan, Ian P. Stolerman, J-a. W. WhiteAbstract:Abstract It has been suggested that use of the AND-OR training method may be associated with an enhancement of the pharmacological specificity of discriminations based on Mixture of Drugs. Rats were trained to discriminate a Mixture of nicotine (0.4 mg/kg s.c.) plus midazolam (0.2 mg/kg s.c.) from saline (AND-discrimination, n = 8) or to discriminate the Mixture from either Drug alone (AND-OR discrimination, n = 6). The studies used two-lever operant procedures with food reinforcers presented on a tandem schedule. After discriminations were acquired to 80% accuracy, the nicotine antagonist mecamylamine (0.03–1.0 mg/kg s.c.) and the benzodiazepine antagonist flumazenil (0.32–10 mg/kg i.p.) were tested on the response to the Mixture of nicotine plus midazolam. The antagonist effects of either mecamylamine or flumazenil given alone were more marked in rats trained under the AND-OR procedure than in rats trained on the AND-discrimination. Similarly, the antagonist effects of Mixtures of mecamylamine plus flumazenil were much more potent under the AND-OR than under the AND-discrimination procedure. The AND-OR method reduced the dose of the antagonist Mixture needed to produce complete block by a factor of about 10, as compared with the AND-discrimination. These striking differences in sensitivity to antagonists support the view that AND-OR or related procedures may enhance the pharmacological specificity of complex Drug discriminations.
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Training dose as a decisive factor for discrimination of a Drug Mixture in rats.
Behavioural pharmacology, 1996Co-Authors: E. A. Mariathasan, J-a. W. White, Ian P. StolermanAbstract:The impact of training dose on the characteristics of a discrimination maintained by a Mixture of two dissimilar Drugs has been investigated in order to refine this approach to the study of Drug interactions. Three groups of rats (n = 10) were trained to discriminate Mixtures of (+)-amphetamine (0.2-0.8mg/kg) plus pentobarbitone (5-20mg/kg) from saline, in a two-lever operant procedure with food reinforcement, with the ratio of the doses held constant (amphetamine: pentobarbitone, 1:25). Discriminations were acquired to an accuracy of 90-97%. There was full generalisation to amphetamine alone, but only in rats trained with Mixtures of the smaller doses of the single Drugs. There was partial generalisation when either apomorphine (50%) or nicotine (63%) was administered alone, and the magnitude of these responses was inversely related to the dose of Mixture used for training. Doses of pentobarbitone half of those used for training produced little discriminative response when administered alone to rats trained with the two smallest doses of the Mixture; the same doses of pentobarbitone increased responses to amphetamine or apomorphine in a more than additive manner. Strikingly, some doses of apomorphine and pentobarbitone that did not generalise when administered separately, produced full generalisation when administered together, but only in rats trained with the smaller doses of the Mixture. In contrast, pentobarbitone did not enhance generalisation to nicotine in any group. It was concluded that, on the one hand, patterns of generalisation to single Drugs followed an orderly pattern resembling those for discriminations established with single Drugs. On the other hand, there was a complex pattern of generalization from one Mixture to another; thus, altering the doses of Drugs used for training markedly influenced discriminations of an abused Drug Mixture, but no simple rules to predict the influence of training dose have been ascertained.
P. Rigatti - One of the best experts on this subject based on the ideXlab platform.
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Four-Drug Intracavernous Therapy for Impotence Due to Corporeal Veno-Occlusive Dysfunction
The Journal of Urology, 1993Co-Authors: F. Montorsi, F. Bergamaschi, G. Guazzoni, Luigi Barbieri, Luigi Ferini-strambi, P. RigattiAbstract:AbstractAlthough veno-occlusive dysfunction is a frequent cause of impotence, a definitive therapeutic strategy has not yet been clearly defined. A total of 56 patients with corporeal veno-occlusive dysfunction diagnosed by dynamic infusion cavernosometry-cavernosography (flow to maintain erection greater than 10ml. per minute and rate of corporeal pressure decrease after interruption of intracavernous infusion greater than 50mm. Hg for 30seconds) not considered suitable candidates for surgery underwent self-injection therapy. A vasoactive Mixture composed of 12.1mg./ml. papaverine hydrochloride, 10.1 µgm/mh prostaglandin E1, 1.01mg./ml. phentolamine mesylate and 0.15mg./ml. atropine sulfate was used. After dose titration of the Drug Mixture 54 patients (95%) were able to obtain sustained rigid erections that guaranteed satisfactory sexual activity. Mean (plus or minus standard error of mean) volume of injected Mixture was 0.42 ± 0.09ml. (range 0.25 to 0.90ml.). Four patients (7%) reported transient hypot...
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Intracavernous four-Drug injection therapy for veno-occlusive dysfunction:
Urologia Journal, 1992Co-Authors: F. Montorsi, F. Bergamaschi, G. Guazzoni, P. Consonimi, Luigi Barbieri, P. RigattiAbstract:Forty patients with erectile impotence due to veno-occlusive dysfunction were treated with intracavernous injection of a four-Drug Mixture composed of: papaverine 12 mg/ml, prostaglandin E1 10 micr...
William R Greco - One of the best experts on this subject based on the ideXlab platform.
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a new nonlinear Mixture response surface paradigm for the study of synergism a three Drug example
Current Drug Metabolism, 2003Co-Authors: Donald B White, Harry K Slocum, Yseult Brun, Carol Wrzosek, William R GrecoAbstract:A flexible approach to response surface modeling for the study of the joint action of three active anticancer agents is used to model a complex pattern of synergism, additivity and antagonism in an in vitro cell growth assay. The method for determining a useful nonlinear response surface model depends upon a series of steps using appropriate scaling of Drug concentrations and effects, raw data modeling, and hierarchical parameter modeling. The method is applied to a very large in vitro study of the combined effect of Trimetrexate (TMQ), LY309887 (LY), and Tomudex (TDX) on inhibition of cancer cell growth. The base model employed for modeling dose-response effect is the four parameter Hill equation [1]. In the hierarchical aspect of the final model, the base Hill model is treated as a function of the total amount of the three Drug Mixture and the Hill parameters, background B, dose for 50% effect D50, and slope m, are understood as functions of the three Drug fractions. The parameters are modeled using the canonical Mixture polynomials from the Mixture experiment methodologies introduced by Scheffe [2]. We label the model generated a Nonlinear Mixture Amount model with control observations, or zero amounts, an “NLMAZ” model. This modeling paradigm provides for the first time an effective statistical approach to modeling complex patterns of local synergism, additivity, and antagonism in the same data set, the possibility of including additional experimental components beyond those in the Mixture, and the capability of modeling three or more Drugs.
