Differential attenuation of d-amphetamine-induced disruption of conditional discrimination performance by dopamine and serotonin antagonists.
BACKGROUND
Recent experimental findings suggest that a core cognitive deficit of schizophrenia is the degraded ability to use task-setting cues to guide goal-directed behaviour, that this deficit is evident in acute as well as chronic schizophrenia, and that such deficits can me modelled in animals using conditional discrimination tasks.


OBJECTIVE
To establish the reversal potential of D1, D2 and 5-HT receptor antagonists acutely, and D1 and D2 receptor antagonists chronically, on d-amphetamine-induced disruption of a conditional discrimination task that depends on the ability to use task-setting cues to direct goal directed performance.


METHODS
A conditional discrimination paradigm was employed in which rats learned to respond on an appropriate lever, conditional upon specific auditory stimuli.


RESULTS
d-Amphetamine (1.5 mg/kg) disruption of conditional discrimination was attenuated by acute pre-treatment with the selective D1 antagonist SCH 23390 and the atypical anti-psychotic clozapine (Cloz). Acute pre-treatment with the selective D2 antagonist eticlopride (Eti) and the anti-psychotic haloperidol (Hal) failed to reverse d-amphetamine disruption, as did pre-treatment with the selective 5HT1A antagonist WAY 100635 and the selective 5HT2A/C antagonist ritanserin. However, Eti and Hal did reverse d-amphetamine-induced task disruption when administered chronically (as did SCH 23390, alpha-flupenthixol and Cloz).


CONCLUSIONS
These results suggest that D1 receptors are involved in tasks that require the use of conditional relationships and that D2 receptor antagonism can come to exert a similar influence after chronic treatment.
Dunn
Michael J
MJ
Centre for Psychology, University of Wales Institute, Cardiff Western Avenue, Cardiff, CF5 2YB, UK. mdunn@uwic.ac.uk
Killcross
Simon
S
D000818:Animals; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D003213:Conditioning, Psychological / Q000187:drug effects*; D003913:Dextroamphetamine / Q000633:toxicity*; D004193:Discrimination Learning / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013997:Time Factors
D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D003913:Dextroamphetamine