An investigation into nicotinic receptor involvement in mood disorders uncovers novel depression candidate genes.

Background: We have previously reported reduced expression of the cholinergic autoreceptor CHRM2 in Brodmann's Area (BA) 24 of the anterior cingulate cortex from subjects with major depressive disorder (MDD) and bipolar disorder (BD), consistent with a hypercholinergic state. This led us to investigate whether levels of the high affinity nicotinic acetylcholine receptors are also altered in BA 24.

Methods: We measured the binding levels of a high-affinity nicotinic receptor-selective radioligand, [H]epibatidine, in BA 24 from subjects with MDD (n = 20), BD (n = 18) and age- and sex-matched controls (n = 20).

The anti-inflammatory selective melanocortin receptor subtype 4 agonist, RO27-3225, fails to prevent acoustic trauma-induced tinnitus in rats.

In preliminary studies we have observed a massive microglial activation in the cochlear nucleus following acoustic trauma-induced tinnitus in rats, which suggests that inflammatory responses within the central auditory system may be involved in the development and maintenance of tinnitus. Recently, the anti-inflammatory properties of melanocortins (MCs), have gained increasing interest in pharmacology due to their promising therapeutic potential in the treatment of inflammatory-mediated diseases. Among the five subtypes of the MC receptor, MC3 and MC4 receptors are the predominant brain receptors and are thought to play an important role in brain inflammation and neuroprotection.

Glutamic acid decarboxylase levels in the cochlear nucleus of rats with acoustic trauma-induced chronic tinnitus.

Tinnitus is the perception of phantom sounds, a phenomenon believed to be due to abnormal neuronal activity in auditory regions of the CNS such as the brainstem cochlear nucleus (CN). One possible mechanism for the abnormal neuronal activity in the CN, supported by recent animal studies, is a decrease in GABAergic inhibition. One possible explanation for this is a decrease in the enzyme responsible for the synthesis of GABA, glutamic acid decarboxylase (GAD).