Discriminative properties of the psychostimulant dl-cathinone in a two lever operant task

Goudie, Andrew J.; Atkinson, Jeffrey; West, Christopher C.

doi:10.1016/0028-3908(86)90063-8

Cited by 34 publications

(14 citation statements)

References 52 publications

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“…The results also confirm that when administered haloperidol, and in spite of obtaining food reward upon lever selection (win), the rats significantly shift responding to the alternative, nonreinforced lever (Colpaert et al, 1977;Goudie et al, 1986). The data extend this finding to other established antipsychotics albeit that the effect did not reach statistical significance with clozapine and risperidone.…”

Section: Discussionsupporting

confidence: 68%

“…Thus, while leaving the ability of conditioned stimuli to control (secondarily reinforced) behavior unaffected, haloperidol blocks the response control that is otherwise exerted by the primary reward; similar findings were obtained in saline-treated but nonrewarded animals (Colpaert et al, 1977;Colpaert, 1987). The haloperidol effect also occurred in rats discriminating the psychostimulant dl-cathinone from saline, indicating that the effect is not specific to the particular stimuli that are being discriminated (Goudie et al, 1986). Likewise, pimozide blocked the food-rewarded pressing of a single lever without affecting motor performance (Wise et al, 1978).…”

supporting

confidence: 55%

“…Indeed, antipsychotics can depress different behaviors, including total responding in the DD paradigm (Colpaert et al, 1977;Goudie et al, 1986), and all the parameters of the paradigm can be fully disrupted by different further agents and neurobiological mechanisms. A striking example is the deterioration by scopolamine of each of the parameters that are assessed before and after lever selection occurs and such that the behavior eventually resembles that seen at the very outset of discrimination training (Colpaert et al, 2001).…”

Section: Methodsmentioning

confidence: 99%

“…Conceivably, therefore, these compounds may share clinical antipsychotic features of haloperidol while avoiding sensitization to extrapyramidal effects. That antipsychotics can selectively block the response control exerted by primary food reward has been demonstrated in the DD (Colpaert et al, 1977;Goudie et al, 1986) as well as in nondiscriminative paradigms (Wise et al, 1978;Ettenberg and Camp, 1986), and these agents reportedly block the reinforcing action of diverse rewards (Salamone et al, 2003;Wise, 2004). It is unclear whether antipsychotics can block the control of negative primary reinforcers in a similarly selective manner; in stark contrast with the present findings, in the conditioned (shock) avoidance paradigm, antipsychotics demonstrate an opposite selectivity, reportedly requiring doses to inhibit the conditioned response that are lower than or equal to, but never higher than, those inhibiting escape (Wadenberg and Hicks, 1999).…”

Section: Win-shift Induction By Antipsychotics 295mentioning

confidence: 98%

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Induction by Antipsychotics of “Win-Shift” in the Drug Discrimination Paradigm

Colpaert

Koek²,

Kleven³

et al. 2007

J Pharmacol Exp Ther

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In a two-lever, food-rewarded drug discrimination paradigm, behavior seems to be governed by a win-stay/lose-shift rule; rats continue to press the lever that yields food, and, when not rewarded, they shift responding to the alternative lever. Here, we report on the effects that antipsychotics and further neuropharmacological agents exert in those conditions. At higher doses, antipsychotics disrupt most or all behavioral parameters in this paradigm. However, at lower doses, rats may select the appropriate lever with normal latency and accuracy, obtain a first food pellet (i.e., "win"), and then, remarkably, shift responding to the alternative lever ("win-shift"). This suggests that antipsychotics can block the effects of reward selectively, i.e., at doses where the initial, secondarily reinforced behavior including the initiation of lever pressing, remains intact. Indeed, saline-treated rats that are given no reward (i.e., "lose") after having selected a lever, also press the alternative lever ("loseshift"). The induction of selective win-shift is specific to antipsychotics, but it varies greatly among them. Perhaps relating to its alleged "incisive" action on delirium and hallucinations, and, surprisingly, in view of its extrapyramidal actions, acutely administered haloperidol (0.04 -0.08 mg/kg) demonstrates win-shift to an exceptional extent, shared only with the newly proposed agent (3-cyclopent-1-enyl-benzyl)-[2-(2,2-dimethyl-2,3-dihydro-benzofuran-7-yloxy)-ethyl]-amine fumarate (F 15063; 0.31-0.63 mg/ kg); the more sedative antipsychotic chlorpromazine demonstrated little selectivity. The paradigm offers a novel tool to characterize antipsychotics with regard to presumably pathogenic motivational processes; mixed D 2 -antagonist/5-hydroxytryptamine 1A -agonist agents such as F 15063 may conceivably share the powerful antipsychotic action of haloperidol while avoiding the sensitization that develops to extrapyramidal effects of haloperidol and consequent negative symptoms.In a typical drug discrimination (DD) experiment, subjects are trained to discriminate a given training drug from saline. For example, rats can be trained to press one of two levers (drug-appropriate lever; DL) for food in sessions preceded by the injection of the opioid fentanyl and to press the alternative lever (saline-appropriate lever; SL) in sessions preceded by saline injection (Colpaert and Janssen, 1984).Rats that have been trained to discriminate fentanyl from saline can demonstrate an exquisite discrimination; the lever selection that is to be made early in the session is correct in nearly 100% of the sessions and occurs with great speed (short latency) and accuracy [the animal pressing the inappropriate lever little if at all before completing the first fixed ration (FR)10 schedule on the appropriate lever]. After having selected the appropriate lever, the rats continue to lever press, totaling some 1500 responses/session, which typically are all made on the appropriate, reward-associated lever (Colpaert, 1978(Colpaert, ...

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Section: Discussionsupporting

confidence: 68%

supporting

confidence: 55%

Section: Methodsmentioning

confidence: 99%

Section: Win-shift Induction By Antipsychotics 295mentioning

confidence: 98%

See 2 more Smart Citations

Induction by Antipsychotics of “Win-Shift” in the Drug Discrimination Paradigm

Colpaert

Koek²,

Kleven³

et al. 2007

J Pharmacol Exp Ther

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“…The procedure was similar to the fixed ratio (FRIO) drug discrimination procedure described by Goudie et al (1986). Subjects were initially trained to press either lever for food reward.…”

Section: Training Procedures For Acquisition Of Amphetaminelsaline Dismentioning

confidence: 99%

Paroxetine, a Selective 5-Hydroxytryptamine Uptake Inhibitor with Antidepressant Properties, Lacks Amphetamine-like Stimulus Properties in an Operant Drug Discrimination Bioassay in Rodents

Goudie

Dubicki

Leathley

1988

Journal of Pharmacy and Pharmacology

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To evaluate whether the novel antidepressant paroxetine has any possible amphetamine-like actions, rats were trained to discriminate (+)-amphetamine sulphate in a standard two lever operant drug discrimination (DD) procedure using a fixed ratio 10 schedule of food reinforcement with a quantal, lever selection, index of the amphetamine stimulus. The 'training' dose of amphetamine was 1 mg kg-1, i.p. Rats trained with this dose of amphetamine (n = 15) learned the drug discrimination rapidly over 30 training sessions and discriminative performance in these animals was subsequently maintained at a high level of accuracy (90% correct) over a prolonged time. In tests in these trained animals, amphetamine itself and the antidepressant agents nomifensine and tranylcypromine all produced clear, unequivocal dose-related generalization to amphetamine with ED50s of 0.2, 0.5 and 1.6 mg kg-1 respectively (as determined by probit analyses). In tests with paroxetine hydrochloride it was established that, over the dose range 0.3 to 10 mg kg-1, no evidence was seen of generalization to the amphetamine stimulus. These data confirm earlier studies which suggested that some antidepressants may possess abuse potential because of their ability to induce amphetamine-like internal states. In contrast, paroxetine is devoid of such properties.

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Drug Discrimination: Practical Considerations

2011

Drug Discrimination

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Discriminative properties of the psychostimulant dl-cathinone in a two lever operant task

Cited by 34 publications

References 52 publications

Induction by Antipsychotics of “Win-Shift” in the Drug Discrimination Paradigm

Induction by Antipsychotics of “Win-Shift” in the Drug Discrimination Paradigm

Paroxetine, a Selective 5-Hydroxytryptamine Uptake Inhibitor with Antidepressant Properties, Lacks Amphetamine-like Stimulus Properties in an Operant Drug Discrimination Bioassay in Rodents

Drug Discrimination: Practical Considerations

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