Morphine Addiction: Sex Differences and the Role of the GABAB Receptors

Morphine has a wide range of pharmacological effects, and its therapeutic use is mainly the treatment of the severe chronic pain. However, morphine treatment has a high risk of developing addiction. Both clinical and preclinical studies have shown that males exhibit a higher analgesic response to morphine administration compared to females. Moreover, clinical studies have shown that women not only need higher doses of morphine to achieve an analgesic effect, but they also have a higher risk of developing addiction. In addition, preclinical studies have reported sex differences regarding the rewarding effects of morphine being female mice more sensitive to morphine rewarding effects. On the contrary, female mice showed a lower intensity in the somatic and motivational expression of morphine withdrawal. GABAB receptors seem to be an attractive potential therapeutic target for preventing and treating morphine addiction. Baclofen, a GABAB receptor agonist, has shown to be effective in treating alcohol and tobacco addiction. On the other hand, preclinical studies have shown that baclofen pretreatment is able to enhance the analgesic effects and prevent morphine rewarding properties. Moreover, baclofen has shown to prevent both the somatic and the motivational component of morphine withdrawal. Taken all together, these studies suggest that baclofen could attenuate the risk of drugs dependence. The purpose of the present chapter will be to address the current evidence regarding sex differences in morphine addiction and the involvement of GABAB receptors in the addictive properties of morphine. This knowledge could be useful for both preclinical and clinical research.