Attenuation of d-amphetamine-induced disruption of conditional discrimination performance by alpha-flupenthixol

Abstract

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 ability to use task-setting cues in schizophrenia.

Objective

To investigate, using the indirect DA agonist d-amphetamine and the D1/D2 receptor antagonist α-flupenthixol, the influence of DAergic manipulation on discrimination performance that requires the use of conditional information to inform goal-directed performance.

Methods

Both instrumental and Pavlovian conditional discriminations were employed in which rats learned to respond appropriately according to the presence of auditory conditional stimuli, and results from these experiments were contrasted with a control Pavlovian-instrumental transfer task.

Results

Experiment 1 showed a disruption of instrumental conditional discrimination performance by d-amphetamine at 1.5 mg/kg and attenuation of correct responding following 1.0 mg/kg. Disruption with both doses was observed in experiment 2 using a conditional discrimination based on Pavlovian, conditioned responding. Results from a control Pavlovian-instrumental transfer task (experiment 3) revealed that d-amphetamine (0.5, 1.0 and 1.5 mg/kg) did not have any detrimental effect on subjects’ basic sensory, motor or motivational processes. Experiment 4 showed that d-amphetamine disruption of instrumental conditional discrimination was attenuated by pre-treatment with the D1/D2 receptor antagonist α-flupenthixol.

Conclusion

These results demonstrate that tasks dependent on conditional relationships are highly sensitive to manipulation of DAergic systems.