Drug discrimination by humans compared to nonhumans: current status and future directions

Kamien, Jonathan B.; Bickel, Warren K.; Hughes, John R.; Higgins, Stephen T.; Smith, Bonnie G.

doi:10.1007/bf02244940

Cited by 113 publications

(59 citation statements)

References 94 publications

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“…The discriminative stimulus effects of psychostimulants in experimental animals are related to their subjective effects in humans (Schuster and Johanson, 1988;Kamien et al, 1993). Therefore, the drug discrimination procedure has been used to elucidate the mechanism of action underlying the unique properties of addictive drugs such as amphetamines and cocaine (Callahan et al, 1997;Munzar and Goldberg, 2000).…”

Section: Effect Of Tnf-␣ On Discriminative Stimulus Effects Of Meth Asupporting

confidence: 42%

Role of Tumor Necrosis Factor-α in Methamphetamine-Induced Drug Dependence and Neurotoxicity

Nakajima¹,

Yamada²,

Nagai³

et al. 2004

J. Neurosci.

162

155

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Section: Effect Of Tnf-␣ On Discriminative Stimulus Effects Of Meth Asupporting

confidence: 42%

Role of Tumor Necrosis Factor-α in Methamphetamine-Induced Drug Dependence and Neurotoxicity

Nakajima¹,

Yamada²,

Nagai³

et al. 2004

J. Neurosci.

162

155

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“…Although exceptions have been noted [Ator et al, 1993;Ator, 1994], there is a strong correlation between discriminative stimuli in non-verbal species and subjective effects reported by humans [Schuster and Johanson 1988;Balster 1990;Sanger et al 1994;Brauer et al 1997]. Although drug-induced stimulus control has been established in humans [for reviews see Kamien et al, 1993;Brauer et al, 1997;Dykstra et al, 1997] and in a number of animal species, the majority of studies have employed the rat [Stolerman and Kamien, 2004]. Nonetheless, the stimulus properties of a number of drugs have been examined in mice as well.…”

Section: Introductionmentioning

confidence: 41%

The stimulus properties of LSD in C57BL/6 mice

Winter¹,

Kieres²,

Zimmerman³

et al. 2005

Pharmacology Biochemistry and Behavior

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Rationale-Drug-induced stimulus control has proven to be a powerful tool for the assessment of a wide range of psychoactive drugs. Though a variety of species have been employed, the majority of studies have been in the rat. However, with the development of techniques which permit the genetic modification of mice, the latter species has taken on new importance. Lysergic acid diethylamide [LSD], the prototypic indoleamine hallucinogen, has not previously been trained as a discriminative stimulus in mice.Objective-To demonstrate the feasibility of LSD-induced stimulus control in the mouse and to provide a preliminary characterization of the stimulus properties of LSD in that species.Methods-Male C57BL/6 mice were trained using a left or right nose-poke operant on a fixed-ratio 10, water reinforced task following the injection of lysergic acid diethylamide [LSD, 0.17 or 0.30 mg/kg, SC; 15 min pretreatment] or vehicle.Results-Stimulus control was established in 6 of 16 mice at a dose of LSD of 0.17 mg/kg after 39 sessions. An increase in dose to 0.30 mg/kg for the remaining mice resulted in stimulus control in an additional 5 subjects. In the low dose group, subsequent experiments demonstrated an orderly dose-effect relationship for LSD and a rapid offset of drug action with an absence of LSD effects 60 min after injection. When LSD [0.17 mg/kg] was administered in combination with the selective 5-HT 2A antagonist, M100907, LSD-appropriate responding was significantly but incompletely reduced to approximately 50%; concurrently, response rates declined significantly. In mice trained with a dose of LSD of 0.30 mg/kg, full generalization to the phenethylamine hallucinogen, [-]-2,5-dimethoxy-4-methylamphetamine [DOM] was observed.Conclusions-The present data demonstrate the feasibility of LSD-induced stimulus control in the mouse. The general features of stimulus control by LSD in the mouse closely resemble those observed in the rat but the present data suggest that there may be significant differences as well.

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“…Drug discrimination is a behavioral tool that is useful for distinguishing a test drug from other drug classes, as well as for distinguishing activity at different opioid receptor systems (Herling andWoods, 1981, Young et al, 1984;Kamien et al, 1993;Dykstra et al, 1997). In prior studies acute tramadol elicited only modest opioid agonist-like subjective effects, suggesting possible nonopioidergic mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Discriminative Stimulus Effects of Tramadol in Humans

Duke¹,

Bigelow²,

Lanier³

et al. 2011

J Pharmacol Exp Ther

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Tramadol is an unscheduled atypical analgesic that acts as an agonist at -opioid receptors and inhibits monoamine reuptake. Tramadol can suppress opioid withdrawal, and chronic administration can produce opioid physical dependence; however, diversion and abuse of tramadol is low. The present study further characterized tramadol in a three-choice discrimination procedure. Nondependent volunteers with active stimulant and opioid use (n ϭ 8) participated in this residential laboratory study. Subjects were trained to discriminate between placebo, hydromorphone (8 mg), and methylphenidate (60 mg), and tests of acquisition confirmed that all volunteers could discriminate between the training drugs. The following drug conditions were then tested during discrimination test sessions: placebo, hydromorphone (4 and 8 mg), methylphenidate (30 and 60 mg), and tramadol (50, 100, 200, and 400 mg). In addition to discrimination measures, which included discrete choice, point distribution, and operant responding, subjective and physiological effects were measured for each test condition. Both doses of hydromorphone and methylphenidate were identified as hydromorphone-and methylphenidate-like, respectively. Lower doses of tramadol were generally identified as placebo, with higher doses (200 and 400 mg) identified as hydromorphone, or opioid-like. The highest dose of tramadol increased ratings on the stimulant scale, but was not significantly identified as methylphenidate-like. Tramadol did not significantly increase subjective ratings associated with reinforcement. Taken together, these results extend previous work with tramadol as a potential medication for the treatment of opioid dependence and withdrawal, showing acute doses of tramadol exhibit a profile of effects similar to opioid agonists and may have abuse liability in certain populations.

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Drug discrimination by humans compared to nonhumans: current status and future directions

Cited by 113 publications

References 94 publications

Role of Tumor Necrosis Factor-α in Methamphetamine-Induced Drug Dependence and Neurotoxicity

Role of Tumor Necrosis Factor-α in Methamphetamine-Induced Drug Dependence and Neurotoxicity

The stimulus properties of LSD in C57BL/6 mice

Discriminative Stimulus Effects of Tramadol in Humans

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