Clozapine, SCH 23390 and alpha-flupenthixol but not haloperidol attenuate acute phencyclidine-induced disruption of conditional discrimination performance
Author
Dunn, Michael
Killcross, Simon
Date
2007-03-01Publisher
Springer
ISSN
0033-3158
Metadata
Show full item recordAbstract
Rationale
Forebrain dopamine (DA) manipulation has recently been shown to selectively disrupt a conditional discrimination task whose design parameters approximate tasks repeatedly shown to be impaired in schizophrenia.
Objective
To investigate the reversal potential of the D1/D2 receptor antagonist α-flupenthixol, the selective D1 antagonist SCH 23390, the typical antipsychotic haloperidol and the atypical antipsychotic clozapine on acute phencyclidine (PCP)-induced disruption of a conditional discrimination task dependent on the ability to use task-setting cues that inform goal-directed performance.
Materials and methods
Rats learned a conditional discrimination task where reinforcement was contingent on an appropriate lever press during a specific auditory stimulus.
Results
PCP disrupted task performance at 1.5 mg/kg, attenuated correct lever pressing at 2.5 mg/kg and abolished overall responding at 5 mg/kg (experiment 1). Pavlovian-instrumental transfer task results (experiment 2) showed that 1.5 and 2.5 mg/kg PCP had no disruptive effects on basic sensory, motor or motivational processes; however, such deficits were evident in 5-mg/kg-treated animals. PCP (1.5 mg/kg) disruption of conditional discrimination was attenuated by acute pretreatment with clozapine, SCH 23390 and α-flupenthixol; however, pretreatment with haloperidol did not attenuate task disruption.
Conclusion
The predictive validity of the conditional discrimination model is enhanced as the selective task disruption by the preeminent psychotomimetic PCP is reversed by clozapine (known to ameliorate cognitive deficits in schizophrenia) and the role of DA D1 receptors as mediators of tasks that require conditional relationships is discussed.
Journal/conference proceeding
Psychopharmacology
Citation
(2007) Psychopharmacology 190 (4), pp.403-414
Collections
- Un-themed [116]
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