Why Do Morphine and Heroin Get You Hooked with Just One Shot?

One dose and you are hooked up.

Researchers have been investigating for a long time the powerful effect of the opioid drugs, like morphine or heroin, in search of a treatment for addiction.

A new Brown University research found morphine to stop the synapse-strengthening in the brain, a phenomenon called long-term potentiation (LTP), at inhibitory synapses. This supports the idea that addiction is a sort of disease of learning and memory.

Just one dose of morphine was found to impede connections at inhibitory synapses. "We've added a new piece to the puzzle of how addictive drugs affect the brain," said lead-researcher Julie Kauer, a professor in the Department of Molecular Pharmacology, Physiology and Biotechnology at Brown. "We've shown here that morphine makes lasting changes in the brain by blocking a mechanism that's believed to be the key to memory making. So these findings reinforce the notion that addiction is a form of pathological learning."

Long-term potentiation (LTP) is critical to this process. LTP has the role of strengthening synapses (connections between neurons), a crucial process in learning , and when it becomes stronger after repeated stimulation, a memory installs.

Morphine's impact on a rat's brain was extremely strong: LTP was still inactive 24 hours later, when the drug was long gone from the animal's system. "The persistence of the effect was stunning. This is your brain on drugs." Kauer said.

The researchers focused on the ventral tegmental area (VTA), a brain nucleus linked to the reward system involved in survival addicting behaviors like eating and sex.

The synapses attacked by the opioid were those linking inhibitory neurons and dopamine neurons. In the normal brain physiology, inhibitory cells decrease dopamine release, the "pleasure chemical" that we get naturally for rewarding experiences. (otherwise, we would be happy when hungry, tortured, ...)

Psychoactive chemicals, from alcohol and nicotine to cocaine, cannabinoids and opioids, also raise dopamine levels. The effect is that opioids, like all drugs, boost the brain's reward chemicals. "It's as if a brake were removed and dopamine cells start firing. That activity, combined with other brain changes caused by the drugs, could increase vulnerability to addiction. The brain may, in fact, be learning to crave drugs."

Besides cellular changes, morphine was found to affect molecule, like the enzyme guanylate cyclase, which regulates the functions of many cell proteins. Effective drugs against opioids should protect this molecule and also target the inhibitory neurons themselves.