Suppressing Glial Cell Activity Reduces Effects of Morphine on Rats

Suppressing Glial Cell Activity Reduces Effects of Morphine on Rats

Glial cells (which are non-neuronal cells that make up the supportive tissue and participate in signal transmission in the nervous system) have recently been shown to help mediate the effects of opioid drugs such as morphine, including analgesia (pain suppression), tolerance, and dependence—effects that were previously thought to be controlled by neurons alone.

To better understand the role glial cells play in morphine’s effects in the brain, researchers funded by the National Institute on Drug Abuse (NIDA) gave rats either twice-daily doses of a drug called ibudilast, which inhibits the activity of glial cells, or a control injection. On the third day, the rats began receiving morphine in increasing doses.

After 5 days of morphine exposure, the rats received a dose of the opioid inhibitor naloxone to induce withdrawal. In contrast to control rats that showed dramatic increases in levels of the chemical dopamine in the nucleus accumbens (NAc) region of the brain in response to morphine injection, rats who had received the ibudilast showed smaller increases.

Moreover, the rats who received ibudilast also showed significantly fewer physical signs of withdrawal after naloxone injection. They also noted that, after naloxone administration, as dopamine levels decreased so did the physical signs of withdrawal.

These results show that inhibiting glial cells with ibudilast can reduce dopamine levels in the NAc, which are considered indicators of morphine reward and may also be associated with withdrawal. Therefore, targeting glial cell activity with drug therapies such as ibudilast may be a promising approach for treating opioid addiction.

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