The effects of morphine (2 mg/kg-60 mg/kg) on cholinergic neuronal activity were examined by the method of high-affinity, Na+-dependent [3H]choline uptake into synaptosomes isolated from mouse corpus striatum. Acute administration of analgesic doses of morphine (10 mg/kg, 20 mg/kg) significantly stimulated choline uptake into synaptosomes in a naloxone-reversible manner. When synaptosomes were directly exposed to pharmacologically effective concentrations of morphine (0.1 microM-10.0 microM) in vitro however, choline transport was not significantly different from control transport, suggesting that morphine (10 mg/kg, 20 mg/kg) does not stimulate choline uptake by a direct effect on the cholinergic nerve terminal. The possibility that acute morphine administration indirectly enhances striatal cholinergic neuronal activity by inhibiting dopaminergic function was supported pharmacologically since the dopaminergic agonists, apomorphine (10 mg/kg) or amantadine (50 mg/kg), reversed the stimulatory effect of morphine on choline uptake. High-affinity choline transport into synaptosomes was not significantly different from control uptake in response to a sub-analgesic dose of morphine (2 mg/kg) or in response to 60 mg/kg, a dose that elicited hypermotility. These data suggest that analgesic doses of morphine may indirectly enhance cholinergic neuronal activity in the mouse corpus striatum.
Amantadine Animals