NRSC 2110 Blog

I?m sure most of us can remember reaching a certain age in high school and having our parents wish we spent more time learning our school material than learning bad habits (such as smoking) from our peers. The irony? The same potentiation that seems to be responsible for the learning and memory that allows us to master our scholastic material may be responsible for our ?learned? addictions. (And our parents thought they could blame the bad kid down the street).

A study (http://www.cell.com/neuron/abstract/S0896-6273%2809%2900580-7) published in the September 2009 issue of Neuron indicates that Dopamine (DA) may be what helps enable our synapses to undergo the types of synaptic plasticity that underlies our addictions and appears to have many similarities to the plasticity underlying our learning and memory including a strong involvement of the hippocampus.

It has been established that both DA signaling and the hippocampal circuitry have a major role in drug addiction. The researchers in this study aimed to study the in vivo synaptic potentiation underlying addiction in awake freely moving animals. Nicotine had already been shown to alter synaptic plasticity, however it had been done in animals that were either anesthetized using an agent that is known to alter the functionality of ligand-gated channels, or given enough nicotine to give an awake mouse a seizure. The researchers here introduce a more physiologically relevant measurement.

In their study, the researchers used the amplitude of the pop spike (PS) (the spike that is produced when a population of cells all fire together) to measure potentiation of synaptic transmission. With the recording electrode placed in the dentate gyrus, they found that when they injected nicotine into mice the PS amplitude showed a significant increase over the baseline animals that were not given nicotine; this indicates that significant synaptic potentiation was induced by nicotine exposure.

Having first established that the nicotine was acting through nicotinic acetylcholine receptors, they injected nicotine directly into the hippocampus. Finding that the nicotine now did not induce a significant change in synaptic potentiation, their results suggest that nicotine must exert its effects in a way that extends beyond the hippocampal circuitry alone.

So where does dopamine fit in to our learned addiction? Well without dopamine our potentiation disappears. When researchers injected a D1-type DA receptor antagonist (both systemically and locally into the hippocampus) the potentiation induced in the hippocampal circuitry by nicotine is inhibited. This strongly suggests that the D1 DA receptors enable the nicotine induced synaptic potentiation. Also of interest, using an agonist of the D2-type DA receptors (these are autoreceptors that will inhibit the firing of midbrain DA delivering neurons when activated) inhibits the nicotine-induced potentiation. However, when an antagonist of the D2-type receptors is used, allowing an even larger DA signal to be delivered from the midbrain, we see enhanced potentiation even beyond the before seen nicotine-induced potentiation. This suggests the magnitude of the DA signal influences the strength of the nicotine-induced potentiation.

How does this translate into memory based behavioral observations? The conditioned place preference (CPP) test was used to find out. When nicotine was administered significant CPP was observed. So it appears they are learning an addiction.

So the next time you see all the college undergrads smoking on their breaks between courses you can appreciate the irony in that the very same synaptic mechanisms allowing them to master their studies allowed them to learn their addiction that interferes with said studies. With the help of DA of course.