Acetylcholinesterase changes in the central nervous system of mice during the development of morphine tolerance addiction and withdrawal.

The distribution of acetylcholinesterase in the brain is studied during the development of morphine tolerance and through a period of withdrawal to elucidate the possible role of this enzyme in producing physical dependence in mice. Tolerance and physical dependence are produced in male albino mice by giving morphine sulphate subcutaneously at eight hourly intervals, in an increasing dose of 10 mg/kg body weight every 24 hours, for 15 days. The animals are considered addicted, when they received an otherwise lethal dose, 150 mg/kg three times a day. The enzyme shows a marked elevation in the overall distribution during the development of physical dependence. The habenular complex, nuclei anterioventralis and medialis thalami, nucleus caudatus putamen, amygdaloideus lateralis, septal nuclei, nucleus nervi hypoglossi, nucleus reticularis lateralis, tuberculum olfactorium, nucleus tractus diagonalis brocae, stratum pyramidale hippocampi, nucleus paraventricularis thalami, nucleus dorsalis nervi vagi, nucleus tractus spinalis nervi trigemini and nucleus reticularis thalami show an increase in the enzyme activity. This enhancement is not linear with the increase in dosage. Withdrawal is characterised by a sudden fall in the activity of acetylcholinesterase in the above mentioned areas of brain.