Increasing D2 Receptors Works On Cocaine, As On Alcohol

Addiction has been linked to a deficiency of dopamine D2 receptors. It appears that scientists have found a way to increase the number of these receptors in the brains of rats:

“By increasing dopamine D2 receptor levels, we saw a dramatic drop in these
rats’ interest in cocaine,” said lead author Panayotis (Peter) Thanos, a
neuroscientist with Brookhaven Lab and the National Institute on Alcohol Abuse
and Alcoholism (NIAAA) Laboratory of Neuroimaging. “This provides new evidence
that low levels of dopamine D2 receptors may play an important role in not just
alcoholism but in cocaine abuse as well. It also shows a potential direction for
addiction therapies.”

The D2 receptor receives signals in the brain triggered by dopamine, a
neurotransmitter needed to experience feelings of pleasure and reward. Without
receptors for dopamine, these signals get “jammed” and the pleasure response is
blunted. Previous studies at Brookhaven Lab have shown that chronic abuse of
alcohol and other addictive drugs increases the brain’s production of dopamine.
Over time, however, these drugs deplete the brain’s D2 receptors and rewire the
brain so that normal pleasurable activities that stimulate these pathways no
longer do – leaving the addictive drug as the only way to achieve this

The current study suggests that cocaine-dependent individuals may have
their need for cocaine decreased if their D2 levels are boosted. Thanos’ lab
previously demonstrated dramatic reductions in alcohol use in alcohol-preferring
rats infused with dopamine D2 receptors (see: Thanos
hypothesized that the same would hold true with other addictive drugs.

The researchers tested this hypothesis by injecting a virus that had been
rendered harmless and altered to carry the D2 receptor gene directly into the
brains of experimental rats that were trained to self-administer cocaine — the
same technique used in the earlier alcohol study. The virus acted as a mechanism
to deliver the gene to the nucleus accumbens, the brain’s pleasure center,
enabling the cells in this brain region to make receptor proteins themselves.

The scientists examined how the injected genes affected the rats’
cocaine-using behavior after they had been taking cocaine for two weeks. After
receiving the D2 receptor treatment, the rats showed a 75 percent decrease in
self-administration of the drug. This effect lasted six days before their
cocaine self-administration returned to previous levels.