Discrimination procedures

Appel, J.B. White, F.J. and Holohean, A.M. Analyzing mechanisms of hallucinogenic drug action with drug discrimination procedures. Neurosci Biobehav Rev 6 529-536, 1982. 

In searching for an animal model specific to PCP and PCP-1i ke agents, the drug discrimination procedure historically has been used. The use of drugs as discriminative stimuli provides a sensitive technique for establishing the similarities among... 

Set up the flow cytometer to acquire red fluorescence signals as pulse width and pulse area (integral) values, so that doublets can be discerned and gated out before analyzing the DNA content frequency histogram (see Wersto et al., 2001, for a discussion of the doublet discrimination procedure). 

More rarely, navigation of a T-maze has been used for drug discrimination studies. Early studies used a T-maze procedure where rats were trained to select one of the two arms when nicotine was administered, whereas entries into the opposite arm were punished by foot-shock (Romano et al. 1981 Schechter and Rosecrans 1971a, b Overton 1982). Nicotine proved to have moderate relative discriminability, as measured by the sessions to criterion performance (20 sessions at 0.55 mg kg Overton 1982). More recently, a food-rewarded discrimination procedure using a T-maze has been described, but no studies involving nicotine have been identified (Colombo et al. 1996). 

Colombo G, Agabio R, Balakhevskaia N, Lobina C, Reah R, Fadda F, Gessa GL (1996) T-maze and food reinforcement an inexpensive drug discrimination procedure. 1 Neurosci Methods 67 83-87... 

Abstract Behavioral discrimination procedures clearly demonstrate that nicotine elicits interoceptive stimulus effects in humans that are malleable by various pharmacological manipulations as well as by some behavioral manipulations. The parameters of nicotine discrimination and both chronic and acute factors that may alter discrimination behavior are addressed in this chapter, which emphasizes research by the author involving nicotine delivered by nasal spray. Human discrimination of nicotine is centrally mediated, as the central and peripheral nicotine antagonist mecamylamine blocks discrimination but the peripheral antagonist trimethaphan does not. The threshold dose for discrimination of nicotine via spray appears to be very low in smokers as well as nonsmokers. Because smoked tobacco delivers nicotine more rapidly than spray, the threshold dose of nicotine via smoking is probably even lower. In terms of individual differences, smokers may become tolerant to the discriminative stimulus effects of higher nicotine doses but not of low doses. 

An alternative method of assessing interoceptive drug effects is the behavioral drug discrimination procedure, which relies on observable behavioral responses to determine whether a drug s stimulus effects have been perceived by the subject (Preston 1991 Overton 1991). Behavioral drug discrimination is widely used in animal studies (Holtzman 1990 see chapter by Stolerman, this volume) because it... 

Shiffman S, Zettler-Segal M, Kassel J, Paty J, Benowitz NL, O Brien G (1992) Nicotine elimination and tolerance in non-dependent cigarette smokers. Psychopharmacology 109 449-456 Singha AK, McCance-Katz EE, Heck SA, Kosten TR, OUveto A (1999) Individual differences in humans responding under a cocaine discrimination procedure discriminators versus nondis-ciiminators. Exper Clin Psychopharmacol 7 391-398 Smith BJ, Bickel WK (1999) The novel-response procedure in humans. Pharmacol Biochem Behav 64 245-250... 

Holter SM, Danysz W, Spanagel R (2000) Novel uncompetitive N-methyl-D-aspartate (NMDA)-receptor antagonist MRZ 2/579 suppresses ethanol intake in long-term ethanol-experienced rats and generalizes to ethanol cue in drug discrimination procedure. J Pharmacol Exp Ther 292 545-552... 

Discriminative stimulus effect. Rhesus monkeys, trained to discriminate A-9-THC from vehicle in a two-lever drug discrimination procedure, were tested with a variety of psychoactive drugs, including cannabinoids or drugs from other classes. The results indicated that A-9-THC discrimination showed pharmacological specificity, in that none of the noncannabinoid drugs fully substituted for A-9-THC. The classical cannabinoids, A-9-THC and A-8-THC, and the novel cannabinoids, WIN and l-butyl-2-methyl-3-(l-naphthoyl)indole, produced full dose-dependent substitution for A-9-THC in all monkeys. A heptyl indole derivative failed to substitute for A-9-THC, but it also did not displace pH] CP-55,940 from its binding site . ... 

A periodically forced system may be considered as an open-loop control system. The intermediate and high amplitude forced responses can be used in model discrimination procedures (Bennett, 1981 Cutlip etal., 1983). Alternate choices of the forcing variable and observations of the relations and lags between various oscillating components of the response will yield information regarding intermediate steps in a reaction mechanism. Even some unstable phase plane components of the unforced system will become apparent through their role in observable effects (such as the codimension two bifurcations described above where they collide and annihilate stable, observable responses). 

Oliveto, A. et al., Butorphanol and nalbuphine in opioid-dependent humans under a naloxone discrimination procedure, Pharmacol. Biochem. Behav., 71, 85, 2002. 

Two basic measures are taken during drug discrimination procedures, the percent responses on the drug-associated lever, both prior to the first reinforcer and for the total session, and the total number of responses per session. 

The principal weakness of drug discrimination procedures for assessing abuse liability is that they provide only indirect evidence regarding abuse. If a test substance is discriminated as being similar to a known drug of abuse, this is taken to indicate that the test substance is likely to be abused in a similar manner. On the other hand, if a test substance does not share discriminative stimulus effects with any known drug of abuse, drug discrimination procedures alone provide no indication of whether the test substance is likely to be abused. 

Meert and Janssen (1989), Meert et al. (1990) showed differences between ritanserin and chlor-diazepoxide in drug discrimination procedures. 

France CP (1995) A sensitive, efficient drug discrimination procedure for studying kappa antagonists in rhesus monkeys. Analgesia 1 421-424... 

Meert TF, de Haes P, Janssen PAJ (1989) Risperidone (R 64 766), a potent and complete LSD antagonist in drug discrimination by rats. Psychopharmacology 97 206-212 Meert TF, de Haes LAJ, Vermote PCM, Janssen PAJ (1990) Pharmacological validation of ritanserin and risperidone in the drug discrimination procedure in the rat. Drug Dev Res 19 353-373... 

There are many alternatives for modeling high pressure phase equilibria. Therefore, it is required a discrimination procedure capable to screen these models satisfactorily. In this work we have compared two discrimination methods in order to select the next experimental point. The first one is the Hunter-Reiner methodology that considers only the predicted response of each model according to the following equations ... 

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