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Amphetamine causes increased wakefulness and focus and increased levels of the 'reward' neurotransmitter, dopamine. Previous studies have shown that a brief period of repeated  exposure to the drug can make healthy people hypersensitive to its effects. This mirrors the enhanced sensitivity to the drug seen in schizophrenia patients. However, the exact effect of this sensitivity on brain function was unknown until now. 

The researchers looked at how information processing in the brain is altered in this sensitised state. They studied 22 healthy male volunteers given amphetamine or a placebo over four sessions. During each session, participants took part in working memory tests while their brains were scanned using functional magnetic resonance imaging (fMRI).

The amphetamine-exposed volunteers became hypersensitive to the drug's effects over the course of the sessions, experiencing greater alertness and faster reaction times.

In terms of brain activity, the researchers saw no change while the subjects were taking tests of low-to-moderate difficulty. However, when the difficulty increased they saw hyperactivity in the brain regions linked to working memory function such as the dorsolateral prefrontal cortex (DLPFC), the striatum and the thalamus. Additionally, an area which is not required for task performance and typically shows reduced activity during such tasks, the superior temporal gyrus, also showed greater activity.

This pattern is similar to that seen in patients with schizophrenia when they perform similar cognitive tasks. It suggests a reduction in the efficiency of brain function in the prefrontal area of the brain.

"The findings are fascinating in that they highlight a potential link between contemporary pharmacological models of schizophrenia, which emphasise dopamine dysregulation, and cognitive models focussing on the disruption of information transmission between cortical regions of the brain," said Dr Owen O'Daly from the Centre for Neuroimaging Sciences at the IoP and lead author of the study.

"Furthermore, it is remarkable that the translation of what was primarily a rodent model of schizophrenia into healthy volunteers should identify regional changes in brain activity that mirror findings from the many patient studies carried out here at the Institute of Psychiatry.”

The study was funded by the Psychiatry Research Trust (PRT) at the Institute of Psychiatry.

‘Functional magnetic resonance imaging investigation of the amphetamine sensitisation model of schizophrenia in healthy male volunteers’ is published in this month’s Archives of General Psychiatry.  To read the paper in full, please follow the link.