Medial prefrontal cortex infusion of alpha-flupenthixol attenuates systemic d-amphetamine-induced disruption of conditional discrimination performance in rats.
BACKGROUND
It has been argued that tasks that necessitate the use of context in the service of goal-directed behaviour are disrupted in both schizophrenic patients and in animal analogues by dopamine (DA) manipulation with the prefrontal cortex being implicated.


OBJECTIVE
To determine the effects on conditional discrimination performance of direct infusion of the DA D(1)/D(2) receptor antagonist alpha-flupenthixol into the medial prefrontal cortex (mPFC) and of its reversal potential on d-amphetamine-induced task disruption.


METHODS
Conditional discrimination performance in which rats learn to respond on an appropriate lever, conditional upon specific auditory stimuli, was acquired and later tested under the above drug treatment protocol in extinction.


RESULTS
Conditional discrimination performance was unaffected by bilateral intra-mPFC alpha-flupenthixol at doses of 12, 24 or 36 microg/microl. A dose of D-amphetamine (1.5 mg/kg) shown previously to disrupt conditional discrimination performance was attenuated by direct PFC infusion of alpha-flupenthixol at doses of 24 and 36 but not 12 microg/microl per site.


CONCLUSIONS
These results show that conditional discrimination performance is at least in part mediated by prefrontal DA as local PFC DA antagonism attenuates task performance disruption by the indirect DA agonist d-amphetamine further implicating the role of dysfunctional forebrain DA in cognitive deficits evident in schizophrenia.
Dunn
Michael J
MJ
Department of Health and Social Sciences (Psychology), University of Wales Institute Cardiff, Llandaff Campus, Western Avenue, Cardiff, CF5 2SG, UK.
Killcross
Simon
S
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003216:Conditioning, Operant; D003913:Dextroamphetamine / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects*; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005475:Flupenthixol / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011954:Receptors, Dopamine / Q000502:physiology; D012559:Schizophrenia / Q000503:physiopathology
D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D005475:Flupenthixol; D003913:Dextroamphetamine