Differential attenuation of d-amphetamine-induced disruption of conditional discrimination performance by dopamine and serotonin antagonists
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Rationale 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. Method 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, α-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.
(2007) Psychopharmacology 188 (2), pp.183-192
Dynodwr Gwrthrych Digidol (DOI)http://dx.doi.org/10.1007/s00213-006-0488-y
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Attenuation of d-amphetamine-induced disruption of conditional discrimination performance by alpha-flupenthixol Dunn, Michael; Bonardi, C; Futter, D; Killcross, Simon (Springer, 2005-01-01)Rationale Previous evidence suggests that manipulation of forebrain dopamine (DA) systems may impair the use of conditional information to inform goal-directed performance, and this may be related to impairments in the ...
Medial prefrontal cortex infusion of alpha-flupenthixol attenuates systemic d-amphetamine-induced disruption of conditional discrimination performance in rats Dunn, Michael; Killcross, Simon (Springer, 2007-06-01)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 ...
Clozapine, SCH 23390 and alpha-flupenthixol but not haloperidol attenuate acute phencyclidine-induced disruption of conditional discrimination performance Dunn, Michael; Killcross, Simon (Springer, 2007-03-01)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 schizophreni ...