The Experts below are selected from a list of 11577 Experts worldwide ranked by ideXlab platform
Michael B Gatch - One of the best experts on this subject based on the ideXlab platform.
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Δ9-Tetrahydrocannabinol-like Discriminative Stimulus effects of five novel synthetic cannabinoids in rats
Psychopharmacology, 2017Co-Authors: Michael B Gatch, Michael J ForsterAbstract:Rationale and objectivesNovel synthetic cannabinoid compounds continue to appear in the market advertised as legal alternatives to marijuana and the older synthetic cannabinoid compounds which are now controlled substances. Most of these newer compounds have been found to act at CB1 receptors, so the purpose of this study was to study the abuse liability of these compounds.MethodsFive of these compounds (BB-22, FUB-PB-22, 5F-AMB, NM2201, and MAB-CHMINACA) were tested for their ability to produce Discriminative Stimulus effects similar to Δ9-tetrahydrocannabinol (Δ9-THC) in rats. The ability of the CB1 receptor inverse agonist rimonabant to antagonize the Discriminative Stimulus effects of the five test compounds was also tested.ResultsAll five of the test compounds fully substituted for the Discriminative Stimulus effects of Δ9-THC at some dose, although MAB-CHMINACA produced an inverted U-shaped dose effect. Rimonabant fully antagonized the Δ9-THC-like Discriminative Stimulus effects of BB-22, 5F-AMB, NM2201, and MAB-CHMINACA but only reduced the effects of FUB-PB-22 to 40–50 % of Δ9-THC-appropriate responding.ConclusionsThese findings suggest that all five of the test compounds produced Δ9-THC-like effects and will likely have abuse liability similar to that of the controlled cannabinoid compounds.
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Locomotor stimulant and Discriminative Stimulus effects of 'bath salt' cathinones.
Behavioural Pharmacology, 2013Co-Authors: Michael B Gatch, Cynthia M. Taylor, Michael J ForsterAbstract:A number of psychostimulant-like cathinone compounds are being sold as 'legal' alternatives to methamphetamine or cocaine. The purpose of these experiments was to determine whether cathinone compounds stimulate motor activity and have Discriminative Stimulus effects similar to those of cocaine and/or methamphetamine. 3,4-Methylenedioxypyrovalerone (MDPV), methylone, mephedrone, naphyrone, flephedrone, and butylone were tested for locomotor stimulant effects in mice and subsequently for substitution in rats trained to discriminate cocaine (10 mg/kg, intraperitoneally) or methamphetamine (1 mg/kg, intraperitoneally) from saline. All compounds fully substituted for the Discriminative Stimulus effects of cocaine and methamphetamine. Several commonly marketed cathinones produce Discriminative Stimulus effects comparable with those of cocaine and methamphetamine, which suggests that these compounds are likely to have similar abuse liabilities. MDPV and naphyrone produced locomotor stimulant effects that lasted much longer than those of cocaine or methamphetamine and therefore may be of particular concern, particularly because MDPV is one of the most commonly found substances associated with emergency room visits because of adverse effects of taking 'bath salts'. Language: en
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Discriminative Stimulus Effects of N,N-Diisopropyltryptamine
Psychopharmacology, 2012Co-Authors: Theresa M. Carbonaro, Michael J Forster, Michael B GatchAbstract:Rationale Serotonergic hallucinogens such as (+)-lysergic acid diethylamide (LSD) and dimethyltryptamine (DMT) produce distinctive visual effects, whereas the synthetic hallucinogen N,N-diisopropyltryptamine (DiPT) is known for its production of auditory distortions. Objective This study compares the Discriminative Stimulus effects of DiPT to those of visual hallucinogens. Methods Adult male rats were trained to discriminate DiPT (5 mg/kg, 15 min) from saline under a FR10 schedule. A dose–effect and time course of DiPT's Discriminative Stimulus effects were established. DMT, (−)-2,5-dimethoxy-4-methylamphetamine (DOM), LSD, (±)-methylenedioxymethamphetamine (MDMA), and (+)-methamphetamine were tested for cross-substitution in DiPT-trained animals. Results Rats learned to discriminate DiPT from saline in an average of 60 training sessions (30 drug and 30 saline). DiPT (0.5–5 mg/kg) produced dose-dependent increases in drugappropriate responding (DAR) to 99 % (ED5002.47 mg/kg). Onset of the Discriminative Stimulus effects was within 5 min, and the effects dissipated within 4 h. Full substitution for the Discriminative Stimulus effects of DiPT occurred with LSD, DOM, and MDMA. DMTonly partially substituted for DiPT (65 % DAR), whereas (+)-methamphetamine failed to substitute for DiPT (29 % DAR). Conclusions The Discriminative Stimulus effects of DiPT were similar those of a number of synthetic hallucinogens, only partially similar to those of DMT, but not similar to (+)methamphetamine. The putative DiPT-induced auditory
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Comparison of the Discriminative Stimulus effects of dimethyltryptamine with different classes of psychoactive compounds in rats
Psychopharmacology, 2009Co-Authors: Michael B Gatch, Theresa M. Carbonaro, Margaret A. Rutledge, Michael J ForsterAbstract:Rationale There has been increased recreational use of dimethyltryptamine (DMT), but little is known of its Discriminative Stimulus effects. Objectives The present study assessed the similarity of the Discriminative Stimulus effects of DMT to other types of hallucinogens and to psychostimulants. Methods Rats were trained to discriminate DMT from saline. To test the similarity of DMT to known hallucinogens, the ability of (+)-lysergic acid diethylamide (LSD), (−)-2,5-dimethoxy-4-methylamphetamine (DOM), (+)-methamphetamine, or (±)3,4-methylenedioxymethyl amphetamine (MDMA) to substitute in DMT-trained rats was tested. The ability of DMT to substitute in rats trained to discriminate each of these compounds was also tested. To assess the degree of similarity in Discriminative Stimulus effects, each of the compounds was tested for substitution in all of the other training groups. Results LSD, DOM, and MDMA all fully substituted in DMT-trained rats, whereas DMT fully substituted only in DOM-trained rats. Full cross-substitution occurred between DMT and DOM, LSD and DOM, and (+)-methamphetamine and MDMA. MDMA fully substituted for (+)-methamphetamine, DOM, and DMT, but only partially for LSD. In MDMA-trained rats, LSD and (+)-methamphetamine fully substituted, whereas DMT and DOM did not fully substitute. No cross-substitution was evident between (+)-methamphetamine and DMT, LSD, or DOM. Conclusions DMT produces Discriminative Stimulus effects most similar to those of DOM, with some similarity to the Discriminative Stimulus effects of LSD and MDMA. Like DOM and LSD, DMT seems to produce predominately hallucinogenic-like Discriminative Stimulus effects and minimal psychostimulant effects, in contrast to MDMA which produced hallucinogen- and psychostimulant-like effects.
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Nicotine and methamphetamine share Discriminative Stimulus effects.
Drug and Alcohol Dependence, 2008Co-Authors: Michael B Gatch, Elva Flores, Michael J ForsterAbstract:Nicotine and methamphetamine are both abused in similar settings, sometimes together. Because there are known interactions between central nicotinic acetylcholine receptors and dopamine receptors, it is of interest to characterize the nature of the interaction of these two compounds in vivo. The purpose of this study was to characterize the extent to which these two compounds produce similar Discriminative Stimulus effects and to identify pharmacological mechanisms for their interaction. Male Sprague-Dawley rats were trained to discriminate methamphetamine or nicotine from saline. First, the ability of methamphetamine and nicotine to cross-substitute in rats trained to the other compound was tested. Subsequently, the ability of a dopamine antagonist (haloperidol) and a centrally acting nicotinic antagonist (mecamylamine) to block the Discriminative Stimulus effects of methamphetamine and nicotine were also tested. Nicotine fully substituted in methamphetamine-trained rats, but methamphetamine only partially substituted in nicotine-trained rats. In nicotine-trained rats, mecamylamine fully antagonized the Discriminative Stimulus effects of nicotine, but haloperidol had no effect. The partial substitution of methamphetamine was partially attenuated by haloperidol, but not altered by mecamylamine. In methamphetamine-trained rats, mecamylamine failed to antagonize the Discriminative Stimulus effects of methamphetamine, but haloperidol fully blocked the methamphetamine cue. Mecamylamine blocked the ability of nicotine to substitute for methamphetamine, but haloperidol had no effect. These results indicate that nicotine and methamphetamine share Discriminative Stimulus effects in some subjects and that the two compounds do not act at the same site, but produce their interaction indirectly. These findings suggest that these two compounds might be at least partially interchangeable in human users, and that there are potentially interesting pharmacological reasons for the commonly observed co-administration of nicotine and methamphetamine.
Michael J Forster - One of the best experts on this subject based on the ideXlab platform.
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Δ9-Tetrahydrocannabinol-like Discriminative Stimulus effects of five novel synthetic cannabinoids in rats
Psychopharmacology, 2017Co-Authors: Michael B Gatch, Michael J ForsterAbstract:Rationale and objectivesNovel synthetic cannabinoid compounds continue to appear in the market advertised as legal alternatives to marijuana and the older synthetic cannabinoid compounds which are now controlled substances. Most of these newer compounds have been found to act at CB1 receptors, so the purpose of this study was to study the abuse liability of these compounds.MethodsFive of these compounds (BB-22, FUB-PB-22, 5F-AMB, NM2201, and MAB-CHMINACA) were tested for their ability to produce Discriminative Stimulus effects similar to Δ9-tetrahydrocannabinol (Δ9-THC) in rats. The ability of the CB1 receptor inverse agonist rimonabant to antagonize the Discriminative Stimulus effects of the five test compounds was also tested.ResultsAll five of the test compounds fully substituted for the Discriminative Stimulus effects of Δ9-THC at some dose, although MAB-CHMINACA produced an inverted U-shaped dose effect. Rimonabant fully antagonized the Δ9-THC-like Discriminative Stimulus effects of BB-22, 5F-AMB, NM2201, and MAB-CHMINACA but only reduced the effects of FUB-PB-22 to 40–50 % of Δ9-THC-appropriate responding.ConclusionsThese findings suggest that all five of the test compounds produced Δ9-THC-like effects and will likely have abuse liability similar to that of the controlled cannabinoid compounds.
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Locomotor stimulant and Discriminative Stimulus effects of 'bath salt' cathinones.
Behavioural Pharmacology, 2013Co-Authors: Michael B Gatch, Cynthia M. Taylor, Michael J ForsterAbstract:A number of psychostimulant-like cathinone compounds are being sold as 'legal' alternatives to methamphetamine or cocaine. The purpose of these experiments was to determine whether cathinone compounds stimulate motor activity and have Discriminative Stimulus effects similar to those of cocaine and/or methamphetamine. 3,4-Methylenedioxypyrovalerone (MDPV), methylone, mephedrone, naphyrone, flephedrone, and butylone were tested for locomotor stimulant effects in mice and subsequently for substitution in rats trained to discriminate cocaine (10 mg/kg, intraperitoneally) or methamphetamine (1 mg/kg, intraperitoneally) from saline. All compounds fully substituted for the Discriminative Stimulus effects of cocaine and methamphetamine. Several commonly marketed cathinones produce Discriminative Stimulus effects comparable with those of cocaine and methamphetamine, which suggests that these compounds are likely to have similar abuse liabilities. MDPV and naphyrone produced locomotor stimulant effects that lasted much longer than those of cocaine or methamphetamine and therefore may be of particular concern, particularly because MDPV is one of the most commonly found substances associated with emergency room visits because of adverse effects of taking 'bath salts'. Language: en
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Discriminative Stimulus Effects of N,N-Diisopropyltryptamine
Psychopharmacology, 2012Co-Authors: Theresa M. Carbonaro, Michael J Forster, Michael B GatchAbstract:Rationale Serotonergic hallucinogens such as (+)-lysergic acid diethylamide (LSD) and dimethyltryptamine (DMT) produce distinctive visual effects, whereas the synthetic hallucinogen N,N-diisopropyltryptamine (DiPT) is known for its production of auditory distortions. Objective This study compares the Discriminative Stimulus effects of DiPT to those of visual hallucinogens. Methods Adult male rats were trained to discriminate DiPT (5 mg/kg, 15 min) from saline under a FR10 schedule. A dose–effect and time course of DiPT's Discriminative Stimulus effects were established. DMT, (−)-2,5-dimethoxy-4-methylamphetamine (DOM), LSD, (±)-methylenedioxymethamphetamine (MDMA), and (+)-methamphetamine were tested for cross-substitution in DiPT-trained animals. Results Rats learned to discriminate DiPT from saline in an average of 60 training sessions (30 drug and 30 saline). DiPT (0.5–5 mg/kg) produced dose-dependent increases in drugappropriate responding (DAR) to 99 % (ED5002.47 mg/kg). Onset of the Discriminative Stimulus effects was within 5 min, and the effects dissipated within 4 h. Full substitution for the Discriminative Stimulus effects of DiPT occurred with LSD, DOM, and MDMA. DMTonly partially substituted for DiPT (65 % DAR), whereas (+)-methamphetamine failed to substitute for DiPT (29 % DAR). Conclusions The Discriminative Stimulus effects of DiPT were similar those of a number of synthetic hallucinogens, only partially similar to those of DMT, but not similar to (+)methamphetamine. The putative DiPT-induced auditory
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Comparison of the Discriminative Stimulus effects of dimethyltryptamine with different classes of psychoactive compounds in rats
Psychopharmacology, 2009Co-Authors: Michael B Gatch, Theresa M. Carbonaro, Margaret A. Rutledge, Michael J ForsterAbstract:Rationale There has been increased recreational use of dimethyltryptamine (DMT), but little is known of its Discriminative Stimulus effects. Objectives The present study assessed the similarity of the Discriminative Stimulus effects of DMT to other types of hallucinogens and to psychostimulants. Methods Rats were trained to discriminate DMT from saline. To test the similarity of DMT to known hallucinogens, the ability of (+)-lysergic acid diethylamide (LSD), (−)-2,5-dimethoxy-4-methylamphetamine (DOM), (+)-methamphetamine, or (±)3,4-methylenedioxymethyl amphetamine (MDMA) to substitute in DMT-trained rats was tested. The ability of DMT to substitute in rats trained to discriminate each of these compounds was also tested. To assess the degree of similarity in Discriminative Stimulus effects, each of the compounds was tested for substitution in all of the other training groups. Results LSD, DOM, and MDMA all fully substituted in DMT-trained rats, whereas DMT fully substituted only in DOM-trained rats. Full cross-substitution occurred between DMT and DOM, LSD and DOM, and (+)-methamphetamine and MDMA. MDMA fully substituted for (+)-methamphetamine, DOM, and DMT, but only partially for LSD. In MDMA-trained rats, LSD and (+)-methamphetamine fully substituted, whereas DMT and DOM did not fully substitute. No cross-substitution was evident between (+)-methamphetamine and DMT, LSD, or DOM. Conclusions DMT produces Discriminative Stimulus effects most similar to those of DOM, with some similarity to the Discriminative Stimulus effects of LSD and MDMA. Like DOM and LSD, DMT seems to produce predominately hallucinogenic-like Discriminative Stimulus effects and minimal psychostimulant effects, in contrast to MDMA which produced hallucinogen- and psychostimulant-like effects.
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Nicotine and methamphetamine share Discriminative Stimulus effects.
Drug and Alcohol Dependence, 2008Co-Authors: Michael B Gatch, Elva Flores, Michael J ForsterAbstract:Nicotine and methamphetamine are both abused in similar settings, sometimes together. Because there are known interactions between central nicotinic acetylcholine receptors and dopamine receptors, it is of interest to characterize the nature of the interaction of these two compounds in vivo. The purpose of this study was to characterize the extent to which these two compounds produce similar Discriminative Stimulus effects and to identify pharmacological mechanisms for their interaction. Male Sprague-Dawley rats were trained to discriminate methamphetamine or nicotine from saline. First, the ability of methamphetamine and nicotine to cross-substitute in rats trained to the other compound was tested. Subsequently, the ability of a dopamine antagonist (haloperidol) and a centrally acting nicotinic antagonist (mecamylamine) to block the Discriminative Stimulus effects of methamphetamine and nicotine were also tested. Nicotine fully substituted in methamphetamine-trained rats, but methamphetamine only partially substituted in nicotine-trained rats. In nicotine-trained rats, mecamylamine fully antagonized the Discriminative Stimulus effects of nicotine, but haloperidol had no effect. The partial substitution of methamphetamine was partially attenuated by haloperidol, but not altered by mecamylamine. In methamphetamine-trained rats, mecamylamine failed to antagonize the Discriminative Stimulus effects of methamphetamine, but haloperidol fully blocked the methamphetamine cue. Mecamylamine blocked the ability of nicotine to substitute for methamphetamine, but haloperidol had no effect. These results indicate that nicotine and methamphetamine share Discriminative Stimulus effects in some subjects and that the two compounds do not act at the same site, but produce their interaction indirectly. These findings suggest that these two compounds might be at least partially interchangeable in human users, and that there are potentially interesting pharmacological reasons for the commonly observed co-administration of nicotine and methamphetamine.
Jenny L. Wiley - One of the best experts on this subject based on the ideXlab platform.
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Discriminative Stimulus properties of δ9 tetrahydrocannabinol thc in c57bl 6j mice
European Journal of Pharmacology, 2009Co-Authors: Robert E. Vann, Jonathan A. Warner, Kristen Bushell, John W. Huffman, B R Martin, Jenny L. WileyAbstract:Primarily, rats have served as subjects in Delta(9)-tetrahydrocannabinol's (THC) discrimination studies although other species such as monkeys and pigeons have been used. While the introduction of the knockout and transgenic mice has vastly stimulated the study of the Discriminative Stimulus effects of drugs there is only a single published report of mice trained to discriminate THC. Thus, this study extended those results by providing a systematic replication that THC serves as an effective Discriminative Stimulus in mice and by further investigating the mechanisms of action involved in the THC discrimination model in the mouse. Male C57BL/6J mice were trained to discriminate 10 mg/kg THC from vehicle in 2-lever drug discrimination. THC fully and dose dependently substituted for itself. Cannabinoid indoles, except one with low cannabinoid CB(1) receptor affinity, substituted for THC. Anandamide failed to substitute for THC when administered alone but completely substituted when administered with the non-specific fatty acid amide hydrolase inhibitor, phenylmethylsulphonyl fluoride. As expected, nicotine failed to substitute for THC. Lastly, the cannabinoid CB(1) receptor antagonist rimonabant blocked THC's Discriminative Stimulus effects. Taken together these studies demonstrate THC's ability to produce Discriminative Stimulus effects as well as demonstrate its pharmacological specificity and mechanism of action in a two-lever drug discrimination mouse model.
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Discriminative Stimulus properties of Δ9-tetrahydrocannabinol (THC) in C57Bl/6J mice.
European Journal of Pharmacology, 2009Co-Authors: Robert E. Vann, Billy R. Martin, Jonathan A. Warner, Kristen Bushell, John W. Huffman, Jenny L. WileyAbstract:Primarily, rats have served as subjects in Delta(9)-tetrahydrocannabinol's (THC) discrimination studies although other species such as monkeys and pigeons have been used. While the introduction of the knockout and transgenic mice has vastly stimulated the study of the Discriminative Stimulus effects of drugs there is only a single published report of mice trained to discriminate THC. Thus, this study extended those results by providing a systematic replication that THC serves as an effective Discriminative Stimulus in mice and by further investigating the mechanisms of action involved in the THC discrimination model in the mouse. Male C57BL/6J mice were trained to discriminate 10 mg/kg THC from vehicle in 2-lever drug discrimination. THC fully and dose dependently substituted for itself. Cannabinoid indoles, except one with low cannabinoid CB(1) receptor affinity, substituted for THC. Anandamide failed to substitute for THC when administered alone but completely substituted when administered with the non-specific fatty acid amide hydrolase inhibitor, phenylmethylsulphonyl fluoride. As expected, nicotine failed to substitute for THC. Lastly, the cannabinoid CB(1) receptor antagonist rimonabant blocked THC's Discriminative Stimulus effects. Taken together these studies demonstrate THC's ability to produce Discriminative Stimulus effects as well as demonstrate its pharmacological specificity and mechanism of action in a two-lever drug discrimination mouse model.
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Nicotine-like Discriminative Stimulus effects of bupropion in rats.
Experimental and Clinical Psychopharmacology, 2002Co-Authors: Jenny L. Wiley, Kari L. Lavecchia, Billy R. Martin, M. I. DamajAbstract:Bupropion, a tobacco-cessation product, shares Discriminative Stimulus effects with cocaine and methamphetamine. The Discriminative Stimulus effects of these drugs, in turn, overlap with those of nicotine. This study investigated the overlap in Discriminative Stimulus effects of bupropion and nicotine. Rats were trained to discriminate 0.4 mg/kg (-)-nicotine from saline in 2-lever drug discrimination. Both nicotine and bupropion substituted for nicotine; however, nicotine's effects were blocked by the nicotinic antagonist mecamylamine, whereas those of bupropion were not. These results suggest that bupropion may be producing its nicotine-like Discriminative Stimulus effects through a different mechanism than nicotine. Given bupropion's shared pharmacology with dopamine transport inhibitors, these effects may be produced in part through bupropion's actions on dopaminergic neurotransmission.
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Discriminative Stimulus effects of CP 55,940 and structurally dissimilar cannabinoids in rats.
Neuropharmacology, 1995Co-Authors: Jenny L. Wiley, Robert L. Balster, R. L. Barrett, J A Lowe, Billy R. MartinAbstract:Abstract CP 55,940 is a potent synthetic bicyclic cannabinoid analog that has been used in a number of studies as a radioligand for the cannabinoid receptor. This compound shares behavioral and biochemical properties with naturally occurring cannabinoids such as Δ9-THC. The purpose of the present study was 3-fold: to establish the ability of CP 55,940 to serve as a Discriminative Stimulus, to determine whether this Discriminative Stimulus is identical to that of Δ9-THC, and to examine whether a newly developed cannabinoid antagonist, SR141716A, would antagonize the Discriminative Stimulus effects of CP 55,940. Rats were trained to discriminate 0.1 mg/kg CP 55,940 from vehicle in standard 2-lever operant conditioning chambers. CP 55,940 produced dose-dependent generalization from the training dose in dose-effect determinations conducted before and after testing with other drugs. The effects of the training dose of CP 55,940 were dose-dependently antagonized by co-administration of SR141716A. Results of substitution tests showed that Δ9-THC, WIN 55,212-2, and cannabinol substituted completely for CP 55,940 in a dose-dependent manner; however, CP 55,940 was approx 10-fold more potent than any of the other drugs in producing CP 55,940-like Discriminative Stimulus effects. Several drugs with CNS depressant properties (phencyclidine, haloperidol and diazepam) failed to produce reliable substitution for CP 55,940. These results demonstrate that CP 55,940 has Discriminative Stimulus effects and that it shares these effects with structurally dissimilar compounds that, like CP 55,940, bind to the cannabinoid receptor. Further, these effects are blocked by SR141716A, a cannabinoid receptor antagonist. The present results provide support for the use of CP 55,940 as a probe for cannabinoid receptor-mediated effects related to cannabis abuse.
Tsutomu Suzuki - One of the best experts on this subject based on the ideXlab platform.
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The Discriminative Stimulus Properties of Hallucinogenic and Dissociative Anesthetic Drugs.
The Behavioral Neuroscience of Drug Discrimination, 2016Co-Authors: Tomohisa Mori, Tsutomu SuzukiAbstract:The subjective effects of drugs are related to the kinds of feelings they produce, such as euphoria or dysphoria. One of the methods that can be used to study these effects is the drug discrimination procedure. Many researchers have been trying to elucidate the mechanisms that underlie the Discriminative Stimulus properties of abused drugs (e.g., alcohol, psychostimulants, and opioids). Over the past two decades, patterns of drug abuse have changed, so that club/recreational drugs such as phencyclidine (PCP), 3,4-methylenedioxymethamphetamine (MDMA), ketamine, and cannabinoid, which induce perceptual distortions, like hallucinations, are now more commonly abused, especially in younger generations. In particular, the abuse of designer drugs, which aim to mimic the subjective effects of psychostimulants (e.g., MDMA or amphetamines), has been problematic. However, the mechanisms of the Discriminative Stimulus effects of hallucinogenic and dissociative anesthetic drugs are not yet fully clear. This chapter focuses on recent findings regarding hallucinogenic and dissociative anesthetic drug-induced Discriminative Stimulus properties in animals.
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Differential substitution for the Discriminative Stimulus effects of 3,4-methylenedioxymethamphetamine and methylphenidate in rats
Journal of Pharmacology and Experimental Therapeutics, 2014Co-Authors: Tomohisa Mori, Naoki Uzawa, Haruyo Kazawa, Hirohiko Watanabe, Ayano Mochizuki, Masahiro Shibasaki, Kazumi Yoshizawa, Kimio Higashiyama, Tsutomu SuzukiAbstract:Previous studies have demonstrated that methylphenidate, MDMA (3,4-methylenedioxymethamphetamine), and other psychostimulants exert stimulant-like subjective effects in humans. Furthermore, MDMA and methylphenidate substitute for the Discriminative Stimulus effects of psychostimulants, such as amphetamine and cocaine, in animals, which suggests that MDMA and methylphenidate may produce similar Discriminative Stimulus effects in rats. However, there is no evidence regarding the similarities between the Discriminative Stimulus effects of MDMA and methylphenidate. To explore this issue, cross-substitution, substitution, and combination tests were conducted in rats that had been trained to discriminate between MDMA (2.5 mg/kg) or methylphenidate (5.0 mg/kg) and saline. In the cross-substitution tests, MDMA and methylphenidate did not cross-substitute for each other. In the substitution test, methamphetamine substituted for the Discriminative Stimulus effects of methylphenidate, but not for those of MDMA. Furthermore, ephedrine and bupropion, which activate dopaminergic and noradrenergic systems, substituted for the Discriminative Stimulus effects of methylphenidate. On the other hand, serotonin (5-HT) receptor agonists 5-HT1A and 5-HT2 fully substituted for the Discriminative Stimulus effects of MDMA. These results suggest that activation of the noradrenergic and dopaminergic systems is important for the Discriminative Stimulus effects of methylphenidate, whereas activation of the serotonergic system is crucial for the Discriminative Stimulus effects of MDMA. Even though MDMA, like psychostimulants, exerts stimulant-like effects, our findings clearly indicate that the Discriminative Stimulus effects of MDMA are distinctly different from those of other psychostimulants in rats.
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Involvement of serotonin receptor mechanisms in the Discriminative Stimulus effects of ketamine in rats.
Journal of Pharmacological Sciences, 2013Co-Authors: Kazumi Yoshizawa, Tomohisa Mori, Minoru Narita, Masahiro Shibasaki, Tamami Ueno, Mizuki Nishiwaki, Norifumi Shimizu, Tsutomu SuzukiAbstract:We have demonstrated previously that the ketamine-induced Discriminative Stimulus effect is likely to reflect the phencyclidine-like psychotomimetic effects. Therefore, the present study was designed to investigate the effects of the antipsychotics and 5-HT2 receptor antagonist on the Discriminative Stimulus effects of ketamine in rats. While sulpiride did not attenuate the Discriminative Stimulus effects of ketamine, both clozapine and ketanserin attenuated those of ketamine, suggesting that the Discriminative Stimulus effects of ketamine are mediated by multiple receptors, especially the 5-HT2 receptor, but not the D2 receptor. Furthermore, our findings imply that atypical antipsychotics could be useful for the treatment of psychotomimetic effects induced by ketamine.
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Discriminative Stimulus effects of hallucinogenic drugs: a possible relation to reinforcing and aversive effects.
Journal of Pharmacological Sciences, 2012Co-Authors: Tomohisa Mori, Masahiro Shibasaki, Kazumi Yoshizawa, Tsutomu SuzukiAbstract:Abstract The subjective effects of drugs are related to the kinds of feelings they produce, such as euphoria or dysphoria. One of the methods that can be used to study these effects is the drug discrimination procedure. Many researchers are trying to elucidate the mechanisms that underlie the Discriminative Stimulus effects of abused drugs (e.g., alcohol, psychostimulants, and opioids). Over the past two decades, the patterns of drug abuse have changed, so that club/recreational drugs such as phencyclidine (PCP), 3,4-methylenedioxymethamphetamine (MDMA), lysergic acid diethylamide (LSD), and ketamine, which induce perceptual distortions, like hallucinations, are now more commonly abused, especially in younger generations. However, the mechanisms of the Discriminative Stimulus effects of hallucinogenic drugs are not yet fully clear. This review will briefly focus on the recent findings regarding hallucinogenic/psychotomimetic drug–induced Discriminative Stimulus effects in animals. In summary, recent research has demonstrated that there are at least two plausible mechanisms that can explain the cue of the Discriminative Stimulus effects of hallucinogenic drugs; one is mediated mainly by 5-HT2 receptors, and the other is mediated through sigma-1 (σ1)-receptor chaperone regulated by endogenous hallucinogenic ligand.
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Behavioral sensitization to the Discriminative Stimulus effects of methamphetamine in rats.
European Journal of Pharmacology, 2004Co-Authors: Tsutomu Suzuki, Tomohisa Mori, Yoshie Fukuoka, Mayumi Miyatake, Minoru NaritaAbstract:Sensitization to the Discriminative Stimulus effects of psychostimulants is not fully understood. Therefore, the present study was designed to investigate the development of sensitization to the Discriminative Stimulus of methamphetamine in rats. A dose-response curve for methamphetamine and a generalization test for cocaine were recorded in rats trained to discriminate between 1.0 mg/kg methamphetamine and saline. A significant leftward shift of the dose-response curve for methamphetamine and of the dose-generalization curve for cocaine was observed following repeated administration of methamphetamine (2.0 mg/kg) instead of saline. These findings suggest that repeated administration of methamphetamine can produce behavioral sensitization to the Discriminative Stimulus effects of methamphetamine in rats.
Robert E. Vann - One of the best experts on this subject based on the ideXlab platform.
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Discriminative Stimulus properties of δ9 tetrahydrocannabinol thc in c57bl 6j mice
European Journal of Pharmacology, 2009Co-Authors: Robert E. Vann, Jonathan A. Warner, Kristen Bushell, John W. Huffman, B R Martin, Jenny L. WileyAbstract:Primarily, rats have served as subjects in Delta(9)-tetrahydrocannabinol's (THC) discrimination studies although other species such as monkeys and pigeons have been used. While the introduction of the knockout and transgenic mice has vastly stimulated the study of the Discriminative Stimulus effects of drugs there is only a single published report of mice trained to discriminate THC. Thus, this study extended those results by providing a systematic replication that THC serves as an effective Discriminative Stimulus in mice and by further investigating the mechanisms of action involved in the THC discrimination model in the mouse. Male C57BL/6J mice were trained to discriminate 10 mg/kg THC from vehicle in 2-lever drug discrimination. THC fully and dose dependently substituted for itself. Cannabinoid indoles, except one with low cannabinoid CB(1) receptor affinity, substituted for THC. Anandamide failed to substitute for THC when administered alone but completely substituted when administered with the non-specific fatty acid amide hydrolase inhibitor, phenylmethylsulphonyl fluoride. As expected, nicotine failed to substitute for THC. Lastly, the cannabinoid CB(1) receptor antagonist rimonabant blocked THC's Discriminative Stimulus effects. Taken together these studies demonstrate THC's ability to produce Discriminative Stimulus effects as well as demonstrate its pharmacological specificity and mechanism of action in a two-lever drug discrimination mouse model.
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Discriminative Stimulus properties of Δ9-tetrahydrocannabinol (THC) in C57Bl/6J mice.
European Journal of Pharmacology, 2009Co-Authors: Robert E. Vann, Billy R. Martin, Jonathan A. Warner, Kristen Bushell, John W. Huffman, Jenny L. WileyAbstract:Primarily, rats have served as subjects in Delta(9)-tetrahydrocannabinol's (THC) discrimination studies although other species such as monkeys and pigeons have been used. While the introduction of the knockout and transgenic mice has vastly stimulated the study of the Discriminative Stimulus effects of drugs there is only a single published report of mice trained to discriminate THC. Thus, this study extended those results by providing a systematic replication that THC serves as an effective Discriminative Stimulus in mice and by further investigating the mechanisms of action involved in the THC discrimination model in the mouse. Male C57BL/6J mice were trained to discriminate 10 mg/kg THC from vehicle in 2-lever drug discrimination. THC fully and dose dependently substituted for itself. Cannabinoid indoles, except one with low cannabinoid CB(1) receptor affinity, substituted for THC. Anandamide failed to substitute for THC when administered alone but completely substituted when administered with the non-specific fatty acid amide hydrolase inhibitor, phenylmethylsulphonyl fluoride. As expected, nicotine failed to substitute for THC. Lastly, the cannabinoid CB(1) receptor antagonist rimonabant blocked THC's Discriminative Stimulus effects. Taken together these studies demonstrate THC's ability to produce Discriminative Stimulus effects as well as demonstrate its pharmacological specificity and mechanism of action in a two-lever drug discrimination mouse model.
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Heroin Discriminative Stimulus effects of methadone, LAAM and other isomers of acetylmethadol in rats
Psychopharmacology, 2002Co-Authors: Jennifer L. Newman, Robert E. Vann, Everette L. May, Patrick M. BeardsleyAbstract:Abstract Rationale. LAAM (α-l-acetylmethadol) is a derivative of the synthetic mu-opiate agonist methadone and is one of the four isomers of acetylmethadol. Methadone and LAAM have similar pharmacological properties and both are approved medications for the treatment of heroin dependency disorders. Few studies have reported on the pharmacology of acetylmethadol's other isomers and most of these have focused on their potential analgesic activity. Objectives. The purpose of the present investigation was to examine the Discriminative Stimulus effects of LAAM, the other isomers of acetylmethadol, and methadone in rats trained to discriminate heroin from water, and to compare the duration of the Discriminative Stimulus effects of heroin, methadone, and LAAM. Methods. Long-Evans rats were trained to discriminate 0.3 mg/kg heroin from water under a fixed ratio 10 (FR10) schedule of food reinforcement. Dose-response functions for heroin, methadone, LAAM, three other isomers of acetylmethadol: α-d-acetylmethadol, β-d-acetylmethadol, β-l-acetylmethadol, and its precursor, β-l-methadol were examined. Additionally, the time course effects for heroin, methadone, and LAAM were examined. Results. LAAM and methadone dose-dependently occasioned heroin-like Discriminative Stimulus effects. Two of acetylmethadol's isomers, α-d-acetylmethadol and β-d-acetylmethadol, were more potent than LAAM in producing heroin-like effects. The β-l-methadol precursor and β-l-acetylmethadol did not fully substitute for heroin's Discriminative Stimulus. LAAM elicited heroin-like Discriminative Stimulus effects for at least 6 h and generated partial generalization up to 36 h following administration. Conclusions. Methadone, LAAM, β-d-acetylmethadol and α-d-acetylmethadol, but not β-l-acetylmethadol and β-l-methadol evoke heroin-like Discriminative Stimulus effects.
