Response of nigral dopamine neurons to actue and prolonged morphine treatment: effect of exposure to cold, physostigmine and nicotine.

The effects of morphine and acute exposure to cold on nigral dopamine (DA) neurons and possible interactions with cholinergic systems were studied by histochemical microfluorimetry in normal and partially morphine-tolerant mice. Morphine (40 mg/kg), cold (4 degrees C), nicotine (1 mg/kg) and physiostigmine (0.25 mg/kg) elicited a rapid rise and subsequent decrease in the fluorescence intensity of DA nerve cells with certain differences in time course. Fastest changes with a peak at 5 min, a marked subsequent drop below control levels and return towards control intensity after 40 min were seen after physostigmine. Antagonisms between various treatments were noted. DA responses correlated well with the time course of behavioural effects, especially after physostigmine. After 3 1/2 days of morphine treatment, the locomotor and analgesic effects of the drug were reduced. At this stage, the initial increase in fluorescence intensity after morphine and the biphasic pattern caused by physostigmine were delayed without any change in response magnitude. Responses to cold and nicotine remained unaltered both in magnitude and time course. Thus, partial tolerance affected the response of nigral DA neurons to some but not all funtional conditions and thereby markedly changed the interaction with cholinergic systems. The difference between physostigmine and nicotine suggests that neuronal circuits including mustcarinic mechanisms are possibly more susceptible to alteration.