Photograph courtesy of John S. Thompson, University of Chicago, Illinois, USA.

Molecules like nicotine, cocaine and morphine stimulate the release of dopamine in the nucleus accumbens — a major reward area of the brain. Not surprisingly, this stimulation seems to be related to the pleasurable feeling that accompanies the intake of these and other drugs of abuse, and to be responsible for their highly addictive nature. The main provider of dopamine to the nucleus accumbens is a mesencephalic nucleus known as the ventral tegmental area (VTA), and we know that, in the case of nicotine, its stimulatory effect is mediated by nicotinic acetylcholine receptors (nAChR) present on the somata of VTA neurons. An unresolved enigma, however, is the fact that although the rewarding effect of nicotine can last for a long time, nAChR desensitize very quickly. Mansvelder and McGehee have put a big piece of this puzzle into place by showing that nicotine not only acts directly on VTA neurons, but that it can also induce a long-lasting potentiation of the excitatory inputs to this nucleus.

Instead of focusing on the dopamine connections of the VTA cells onto the nucleus accumbens, Mansvelder and McGehee decided to investigate the effect of nicotine on the glutamate synapses received by the VTA from structures such as the prefrontal cortex. They observed that, in the absence of any other manipulation, a brief application of nicotine increased the amplitude of the excitatory synaptic currents through a presynaptic mechanism. This effect was short-lived and had previously been found in other brain regions. However, if they applied nicotine and depolarized the VTA neurons simultaneously, the potentiation of the currents showed an uncanny resemblance to long-term potentiation (LTP) in the CA1 region of the hippocampus — it lasted for long periods, it was sensitive to the presence of N-methyl-d-aspartate receptor antagonists, and it required the depolarization of the postsynaptic neuron.

The glutamate input to the VTA is known to influence the nicotine-induced enhancement of dopamine release in the nucleus accumbens, and it is likely that the potentiation unveiled by Mansvelder and McGehee plays a role in this phenomenon. It will be of interest to determine whether there is a behavioural correlate of this form of plasticity by testing, for instance, if nicotine self-administration actually depends on the induction of the potentiation. More importantly, one might wonder whether a similar potentiation is observed with other drugs of abuse such as heroin, which also increases dopamine release in the reward areas of the brain but is much more addictive. Clearly, those already addicted to the study of LTP will now find it even harder to kick the habit.