The glutamate release inhibitor riluzole attenuates the formation of conditioned place aversion induced by naloxone in rats undergoing a single morphine exposure

Acute morphine exposure has been hypothesized to produce long-lasting central changes that contribute to the withdrawal aversion. We have most recently demonstrated that those changes may involve the glutamatergic system, including multiple classes of receptors. The present study was undertaken to further determine the involvement of the glutamatergic system by examining the effect of riluzole, a glutamate release inhibitor, on the motivational component of withdrawal from acute morphine dependence. The role of the amygdala in the action of riluzole was also assessed. We investigated the effects of riluzole on the conditioned place aversion (CPA) induced by naloxone-precipitated withdrawal from a single morphine exposure 24 h before, and on c-Fos expression within the amygdala during the withdrawal period in rats. Riluzole (2, 4, 8 mg/kg) dose-dependently attenuated the CPA without producing place conditioning itself. This result provided further evidence that glutamatergic mechanisms may be recruited in adaptational changes following acute morphine exposure and play a role in withdrawal aversion. In addition, riluzole appeared to produce nonspecific effects on c-Fos expression by itself, without specifically modifying c-Fos expression following naloxone-precipitated withdrawal in any region of the amygdala examined, suggesting that the amygdala may not serve as a specific site of action for riluzole.