Cyclic AMP-induced changes in the electroencephalogram and in behavior during morphine dependence and abstinence in the rat.

Rats were prepared with permanent electrodes for recording activities of the electroencephalogram (EEG) and electromyogram (EMG) and made morphine dependent by the subcutaneous implantation of two morphine pellets. Abstinence was then precipitated by removal of the pellets 72 hr later. During the first 2 days after pellet implantation, high voltage slow activity appeared in the EEG during behavioral wakefulness and stupor, and sleep and REM sleep were greatly reduced. By the third day, tolerance to these effects developed. After pellet removal, REM sleep time during the first day was reduced. Wet dog shake activity reached a maximum during the second day of abstinence. Treatment of rats with cyclic adenosine 3',5'-monophosphate (cAMP), 50 mg/kg intraperitoneally once daily prior to and during induction of morphine dependence and during withdrawal, markedly reduced the appearance of morphine-induced high voltage EEG slow activity after implantation of the morphine pellets. Behavioral arousal during the first 2 days after pellet implantation, on the other hand, was increased. After removal of the morphine pellets, sleep episodes occurred less frequently during the first day than in the control rats. The incidence of wet shakes at this time was also elevated. These results provide direct evidence for an involvement of brain cAMP in the mediation of the central effects of morphine.