Responsivity of lateral septum-mPFC connections in alloxan-induced hyperglycemia

The lateral septal nucleus (LSN) is related to the actions of antidepressants, and the prelimbic cortex (PL) and infralimbic cortex (IL) modulate responses to fear. However, unknown is whether experimental diabetes that is induced by alloxan alters the responsivity of these regions. We used a method in which one forebrain region (LSN) was electrically stimulated while single-unit extracellular recordings were performed in another mPFC region (PL and IL). Several experimental groups were tested: (a) animals that were subjected to long-term (42-day) alloxan-hyperglycemia and protected with insulin, (b) healthy animals that received a low dose of insulin that does not produce changes in glycemia, and (c) animals that received long-term treatment with fluoxetine. Additional healthy groups of animals received insulin or fluoxetine and underwent the forced swim test. Biological measurements indicated the induction of diabetes in alloxan-treated rats. In this group, a shift toward an inhibitory response to LSN stimulation was observed in the PL and IL compared with the control group. A low dose of insulin or fluoxetine produced similar changes in LSN-PL and LSN-IL responsivity. Long-term hyperglycemia increased inhibitory responsivity in the LSN-PL and LSN-IL, but this action was less pronounced than the action that was exerted by insulin and fluoxetine, which produced similar actions. Such similar actions were confirmed in the forced swim test, in which the antidepressant-like effects of insulin partially resembled the effects of fluoxetine. The changes that were observed in the alloxan group appeared to be related to neuronal damage, and a low dose of insulin exerted some antidepressant-like actions.