Effect of gabapentin-like compounds on development and maintenance of morphine-induced conditioned place preference

Rationale: Psychological dependence to the opioid analgesic morphine is att ributable to the rewarding properties of the drug, and its evolution can be divided into two distinct phases: development and maintenance. Both phases can be studied using conditioned place preference (CPP). Objectives: To de termine whether the two phases can be influenced by pre-treatment with gaba pentin-like compounds. Methods: CPP to morphine was used to demonstrate the rewarding properties of morphine in the presence or absence of gabapentin- like compounds. In-vivo microdialysis in the nucleus accumbens was used to determine the effects of gabapentin or pregabalin on morphine-induced dopam ine release. Results: Pretreatment with either gabapentin (10-100 mg/kg p.o .) or pregabalin (3-30 mg/kg p.o.) attenuated CPP induced by a submaximal d ose of morphine (0.75 mg/kg). Neither gabapentin nor pregabalin had any eff ect alone in the CPP test. Both gabapentin-like compounds blocked the effec t of morphine (0.75 mg/kg s.c.) to increase the release of dopamine in the nucleus accumbens. Studies of the maintenance of CPP to morphine showed CPP was maintained for at least 4 days after the initial test. In a second exp eriment, it was found that pregabalin (injected once, 24 h after CPP had be en demonstrated) was able to reverse morphine-induced CPP. Conclusions: Nei ther gabapentin nor pregabalin induced CPP, but both compounds blocked the development of CPP to morphine and also blocked morphine's effects on dopam ine release. Furthermore, pregabalin blocked the maintenance of morphine-in duced CPP. It is concluded that gabapentin-like compounds, which have no in trinsic rewarding properties, may have some therapeutic use in the treatmen t of opioid dependence.