Generalization testing with atypical and typical antipsychotic drugs in rats trained to discriminate 5.0 mg/kg clozapine from vehicle in a two-choice drug discrimination task

2005 ◽  
Vol 64 (1) ◽  
pp. 55-65 ◽  
Author(s):  
Adam J. Prus ◽  
Scott D. Philibin ◽  
Alan L. Pehrson ◽  
Chad L. Stephens ◽  
Rhiannon N. Cooper ◽  
...  
Keyword(s):  
Drug Discrimination ◽  
Discrimination Task ◽  
Antipsychotic Drugs ◽  
Typical Antipsychotic ◽  
Generalization Testing

Clozapine: A Hypothesised Mechanism for its Unique Clinical Profile

1992 ◽  
Vol 160 (S17) ◽  
pp. 17-21 ◽  
Author(s):  
Benjamin S. Bunney
Keyword(s):  
Antipsychotic Drugs ◽  
Research Data ◽  
Clinical Profile ◽  
Typical Antipsychotic ◽  
Dopamine System ◽  
Nigrostriatal Dopamine ◽  
Midbrain Dopamine

Clozapine's clinical profile is unique among antipsychotic drugs. What makes it different? For almost two decades researchers have been attempting to answer this question. Based on various data, many hypotheses have been proposed. Using electrophysiological techniques we have found that clozapine, like typical antipsychotic drugs, inactivates most midbrain dopamine cells secondary to the induction of depolarisation block. However, unlike classical antipsychotic drugs, clozapine does not inactivate the nigrostriatal dopamine system. Based on these and other findings the hypothesis of ‘depolarisation block‘ is reviewed and presented as an explanation for clozapine's unique clinical profile. Research data both for and against the hypothesis are then discussed.

Quantal Nature of Generalization and Acquisition Responding by Rats in a Drug Discrimination Task

1987 ◽  
Vol 37 (2) ◽  
pp. 161-165 ◽  
Author(s):  
D. A. Mathis ◽  
M. W. Emmett-Oglesby ◽  
C. M. Harris ◽  
H. Lal
Keyword(s):  
Drug Discrimination ◽  
Discrimination Task

Discriminative stimulus, subject-rated and cardiovascular effects of cocaine alone and in combination with aripiprazole in humans

2010 ◽  
Vol 25 (11) ◽  
pp. 1469-1479 ◽  
Author(s):  
Joshua A Lile ◽  
William W Stoops ◽  
Paul EA Glaser ◽  
Lon R Hays ◽  
Craig R Rush
Keyword(s):  
Heart Rate ◽  
Drug Discrimination ◽  
Discriminative Stimulus ◽  
Discrimination Task ◽  
Partial Agonist ◽  
Cardiovascular Effects ◽  
Behavioral Effects ◽  
Acute Administration ◽  
Duration Of Treatment ◽  
Stimulant Use

Aripiprazole is a dopamine D2 receptor partial agonist undergoing evaluation as a pharmacotherapy for stimulant-use disorders. Acutely administered aripiprazole attenuates the discriminative stimulus and other behavioral effects of d-amphetamine in humans; however, whether aripiprazole attenuates the effects of more commonly abused stimulants is unknown. The aim of this experiment was to assess the discriminative stimulus, subject-rated and cardiovascular effects of oral cocaine alone and following acute administration of aripiprazole in humans. Eight cocaine-dependent subjects learned to discriminate 150 mg cocaine from placebo. After acquiring the discrimination, the effects of cocaine (0, 25, 50, 100 and 200 mg) administered alone and in combination with aripiprazole (15 mg) were determined. Significant effects of cocaine were observed for the drug discrimination task, stimulant-like subject-rated effects and heart rate. Limited effects of aripiprazole were revealed. However, for most measures, fewer doses of cocaine were significantly greater than placebo when combined with aripiprazole, suggesting a reduction in the discriminative stimulus, self-reported and cardiovascular effects of cocaine. These data are consistent with previous studies that have tested acutely administered aripiprazole in combination with d-amphetamine and suggest that the ability of aripiprazole to modify stimulant effects is a function of the duration of treatment (acute vs. chronic).

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