The burst of energy and hyperactivity that comes with a cocaine high is a rather accurate reflection of what is going on in the brain of its users, a new study has found.
Researchers conducted experiments in rats exposed to cocaine and mapped out the network of circuits that cause wild firing of neurons that produce dopamine.
The findings also help explain how cocaine use eventually leads to desensitisation.
The researchers used tracer molecules to follow electrical activity in the brain in rats exposed to cocaine.
They found that a hub of neurons in the extended amygdala (the brain's motivation/learning centre) acts as a relay between activation of the ventral subiculum (the brain's addiction centre) and the hyperactive release of dopamine.
Over time, increasing activation of a key part of the extended amygdala - the bed nucleus of the stria terminalis - produces a long-lasting increase in signal transmission onto neurons that produce dopamine so that the rats became desensitised to the cocaine.
Since this change happens within the amygdala, it may explain some of the long-term effects on behaviour and motivation that occur after prolonged cocaine use.
"Unravelling the neuronal circuit and characterising the synaptic mechanisms by which the ventral subiculum alters the excitability of dopamine neurons is a necessary first step in understanding the resulting behavioural changes induced by cocaine," said Francois Georges of Bordeaux University in France.
"We show that the ventral subiculum recruits the bed nucleus of the stria terminalis to drive a persistent hyperactivity of dopamine neurons and control cocaine-induced activity," he added.
A single stimulation of the ventral subiculum (which lasts about 10 minutes in an anaesthetised rat) had the same impact on the brain and dopamine neurons as a massive injection of cocaine.
These effects lasted up to five days and raise the possibility that dopamine-producing neurons can be changed so that they respond differently to stimuli.
The study was published in the journal Cell Press.
