Autoradiographic distribution of cholinergic muscarinic receptors and serotonin₂ receptors in olfactory bulbectomized (OB) rats after chronic treatment with mianserin and desipramine

Bilateral removal of the olfactory bulbs in rats produces a behavioural abnormality that is defined by hyperactivity in the open‐field test. This abnormality may be related to depression since these behavioural effects can be attenuated by antidepressant drugs. Moreover, changes in the cholinergic and serotonergic system may be involved in the pathogenesis of depression. Thus, muscarinic cholinergic and serotonin 2 receptors were measured by quantitative autoradiography after the bilateral removal of the olfactory bulbs from the rat. In OB rats, muscarinic receptor density was decreased in several brain regions including the amygdaloid cortex, the basal ganglia, hippocampus, hypothalamus, cortex and olfactory regions. Serotonin 2 receptors were increased in all cortical regions, in the hippocampus and the thalamus. When OB rats were treated chronically for 35 days with mianserin (5 mg/kg i. p.) or desipramine (7·5 mg/kg i. p.) the behavioural hyperactivity was reversed and muscarinic receptor density was increased in the hippocampus and cortical regions while serotonin 2 receptors were normalized. The results are consistent with a cholinergic and serotonin involvement in depressive illness and suggest that the cholinergic and serotonergic modulatory properties of antidepressant drugs may contribute to their therapeutic effectiveness.