N-acetylcysteine amide (AD4) reduces cocaine-induced reinstatement - Prof. Daphne Atlas

We prepared a non-toxic small-molecular weight compound, with combined anti-inflammatory, and metal chelating activities.  The new compound is the amide form of N-acetylcysteine (NAC).   NAC itself is being used in the clinic for over 40 years but displays a relatively low efficacy.

The amide form of NAC, NAC-amide, is called AD4 or NACA, and is highly effective because it is both water-soluble and crosses cell membranes.  A large number of in vivo and in vitro studies have shown that AD4 is significantly more effective than NAC.

In this new study, AD4 (NAC-amide) was examined in intravenous cocaine self-administration and extinction/reinstatement procedures in rats.

We investigated the behavioral effects of AD4 in the olfactory bulbectomized (OBX) rats, considered an animal model of depression. We also tested rats injected with AD4 or NAC during 10-daily extinction training sessions to examine subsequent cocaine seeking.

We found that AD4 is highly effective in reducing cocaine-induced reinstatement in rats with preexisting depression. It is more potent than NAC in reducing cocaine-induced reinstatement in rats with preexisting depression

AD4 is very effective because it was also shown to inhibit metalloproteinase 9 (MMP-9), which is required for cocaine relapse and relapse-associated synaptic plasticity

AD4 treatment represents a new approach to treat substance-use disorders through affecting the glutaminergic pathway aimed at improving the dopaminergic system.  In addition AD4 helps the cells to better manage drug-induced changes through increasing the reductive state and lowering inflammatory insults.

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