Background:
Decreased [3H]pirenzepine binding to cortical M1 receptors is a consistent finding in subjects with schizophrenia (Crook et al. Am J Psychiatry 2001, 158 918–925), but the mechanisms causing such decreases are unknown. Recently, low levels of cortical M1 receptors have been reported in mu-opioid receptor knockout mice (Yoo et al. Synapse 2004, 54 72–82), suggesting that receptor has a role in regulating levels of cortical M1 receptors. We have therefore determined levels of cortical mu-opioid receptors in three cohorts (1 = controls, 2 = schizophrenia with normal levels of [3H]pirenzepine binding, 3 = schizophrenia with low levels of [3H]pirenzepine binding) to determine if decreased mu-opioid receptors are associated with low levels of M1 receptors in schizophrenia.
Methods:
Western blotting with a rabbit anti-mu-opioid receptor antibody was used to measure the levels of mu-opioid receptor in Brodmann's area (BA) 9 from 20 subjects from each of the three cohorts described above.
Results:
There was no significant difference (P = 0.79) between levels of mu-opioid receptors in the controls (0.98 ± 0.10) and either of the two cohorts of subjects with schizophrenia (cohort 3: 1.01 ± 0.11, cohort 2: 1.01 ± 0.19).
Conclusions:
These data suggest that, at least in BA 9, the mu-opioid receptor is not altered in subjects with low levels of [3H]pirenzepine binding and probably does not play a direct role in the regulation of the muscarinic M1 receptor in subjects with schizophrenia.
