Upregulated arachidonic acid signalling in the olfactory bulbectomized rat model of depression

The olfactory bulbectomized rat is an animal model of depression with a number of neurochemical, neuroendocrinological and behavioural features resembling human depression. Arachidonic acid (AA) is a second messenger released from the neuronal membrane phospholipids following the stimulation of the receptors coupled with G-proteins to the cytosolic phospholipase A (cPLA2) signalling pathway. The signalling of several neurotransmitter systems which are deregulated in OBX rats (serotonergic, dopaminergic, cholinergic, and glutamatergic) converges on the cPLA2 signalling pathway. The aim of the present study was to assess the incorporation coefficient k* [ml/g/s] of AA in a large number of brain regions in the OBX rat, as a parameter reflecting AA turnover. Male Sprague–Dawley rats (160–200 g) were randomly assigned into an intact Sprague–Dawley (SPD) group, a Sham-operated (SHAM) group or an olfactory bulbectomized (OBX) group (n = 5 per group). Two weeks following the surgeries (SHAM and OBX rats) or without any prior intervention (SPD rats), the k* was measured using [1-14C] AA autoradiography. Two-way ANOVA followed by the Newman–Keuls test revealed the following: (1) significantly increased AA turnover in the OBX rats, relative to the SHAM rats, in 17 out of 27 assessed brain regions; and (2) no significant differences in AA turnover between the SHAM and the SPD rats. The results suggest the upregulation of one or more neurotransmitter systems or receptors acting through the PLA2 signalling pathway, or the components of the cPLA2 signalling system itself. Taken together with the previous measurements, one can conclude that this elevation is likely related to upregulation in the brain serotonergic system because of the elevated 5-HT synthesis of the OBX rats.

Research highlights▶ Upregulation in the arachidonic acid (AA) uptake in the brain of OBX rats is found. ▶ The upregulation of the AA turnover could relate to the elevation of 5-HT synthesis in the OBX rats.