In the present study, the involvement of the selective
adenosine A1 (CPA) and A2A (
CGS 21680) and non-selective
adenosine A1/A2A (
NECA) receptor agonists on the development of
hypersensitivity to acute
morphine injection given during
opiate withdrawal was investigated. Intraperitioneal (ip)
injections of
morphine at increasing doses (10, 20, 30, 40, 50 mg/kg) for 6 consecutive days produced a state of dependence. On the 6th day, in the morning, animals were injected with the last dose of
morphine (50 mg/kg, ip). Each day, 20 min before each injection of
morphine,
adenosine receptor agonists were also administered. Seven days after cessation of the
morphine treatment, on the 13th day of the experiment, all animals were challenged with a dose of
morphine (10 mg/kg, ip). A clear increase in locomotor activity was observed, indicating that
hypersensitivity had developed. Our study has demonstrated the presence of an attenuating effect of adenosinergic drugs, such as
CGS 21680 and
NECA, but not CPA, on the development of
hypersensitivity. The results indicate that stimulation of the
adenosine A2A receptor plays some role in modulating the neuroadaptive changes appearing during chronic
opioid treatment and that
adenosine A2A receptor agonists may serve as useful drugs in relapse protection. Our investigations focused on
adenosine A2A agonists as possible vehicles for
pharmacotherapy for
morphine addiction.