A GABA_B agonist reverses the behavioral sensitization to morphine in rats

Rationale: In laboratory animals, repeated administration of drugs of abuse causes sensitization to their stimulant and rewarding effects. Neuroadaptations underlying sensitization could be related to those that contribute to addictive behaviors. An increased understanding of the molecular mechanisms of sensitization could lead to improved treatments for addiction. Objectives: Since baclofen (BCF) co-administration has been reported to block the development and the expression of motor sensitization to morphine (MOR), the present study examined the hypothesis that a chronic treatment with BCF alone might reverse and/or prevent MOR-induced sensitization. Methods: Rats were first sensitized to MOR (saline or 10 mg/kg MOR i.p.; days 1-10) and then chronically treated with BCF (saline or 2 mg/kg BCF i.p.; days 11-20). Finally, the motility effect of MOR (10 mg/kg i.p.) was assessed 3 and 30 days after the end of BCF treatment. The same rats were again challenged with MOR on day 70, after a further period of saline or MOR treatment (days 51-60). Results: Behavioral sensitization to MOR was observed in control animals but not in rats chronically treated with BCF (days 23 and 50). Thus, BCF completely reversed MOR-induced sensitization, and its effect was long lasting. However, a previous repeated BCF treatment did not prevent the development of sensitization to MOR both in naive and desensitized rats. Conclusions: The present results confirm that γ-aminobutyric acid (GABA)_B receptors play an important role in the expression of motor sensitization to MOR and suggest that GABA_B agonists could be useful for reversing the neuroadaptations related to drug addiction.